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1.  The importance of cognitive aging for understanding dementia 
Age  2010;32(4):509-512.
A third of those over 80 years of age are likely to have dementia, the lack of a cure requires efforts directed at prevention and delaying the age of onset. We argue here for the importance of understanding the cognitive ageing process, seen as the decline in various cognitive functions from adulthood to old age. The impact of age on cognitive function is heterogeneous and the identification of risk factors associated with adverse cognitive ageing profiles would allow well targeted interventions, behavioural or pharmacological, to delay and reduce the population burden of dementia. A shift away from binary outcomes such as dementia assessed at one point in time in elderly populations to research on cognitive ageing using repeated measures of cognitive function and staring earlier in the lifecourse would allow the sources of variability in ageing to be better understood.
doi:10.1007/s11357-010-9147-7
PMCID: PMC2980594  PMID: 20454932
Aging; Alzheimer Disease; epidemiology; physiopathology; Cognition; Dementia; diagnosis; epidemiology; physiopathology; prevention & control; therapy; France; epidemiology; Humans; Prevalence; Risk Factors; World Health Organization
2.  Caregiver- and Patient-Directed Interventions for Dementia 
Executive Summary
In early August 2007, the Medical Advisory Secretariat began work on the Aging in the Community project, an evidence-based review of the literature surrounding healthy aging in the community. The Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the ministry’s newly released Aging at Home Strategy.
After a broad literature review and consultation with experts, the secretariat identified 4 key areas that strongly predict an elderly person’s transition from independent community living to a long-term care home. Evidence-based analyses have been prepared for each of these 4 areas: falls and fall-related injuries, urinary incontinence, dementia, and social isolation. For the first area, falls and fall-related injuries, an economic model is described in a separate report.
Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html, to review these titles within the Aging in the Community series.
Aging in the Community: Summary of Evidence-Based Analyses
Prevention of Falls and Fall-Related Injuries in Community-Dwelling Seniors: An Evidence-Based Analysis
Behavioural Interventions for Urinary Incontinence in Community-Dwelling Seniors: An Evidence-Based Analysis
Caregiver- and Patient-Directed Interventions for Dementia: An Evidence-Based Analysis
Social Isolation in Community-Dwelling Seniors: An Evidence-Based Analysis
The Falls/Fractures Economic Model in Ontario Residents Aged 65 Years and Over (FEMOR)
This report features the evidence-based analysis on caregiver- and patient-directed interventions for dementia and is broken down into 4 sections:
Introduction
Caregiver-Directed Interventions for Dementia
Patient-Directed Interventions for Dementia
Economic Analysis of Caregiver- and Patient-Directed Interventions for Dementia
Caregiver-Directed Interventions for Dementia
Objective
To identify interventions that may be effective in supporting the well-being of unpaid caregivers of seniors with dementia living in the community.
Clinical Need: Target Population and Condition
Dementia is a progressive and largely irreversible syndrome that is characterized by a loss of cognitive function severe enough to impact social or occupational functioning. The components of cognitive function affected include memory and learning, attention, concentration and orientation, problem-solving, calculation, language, and geographic orientation. Dementia was identified as one of the key predictors in a senior’s transition from independent community living to admission to a long-term care (LTC) home, in that approximately 90% of individuals diagnosed with dementia will be institutionalized before death. In addition, cognitive decline linked to dementia is one of the most commonly cited reasons for institutionalization.
Prevalence estimates of dementia in the Ontario population have largely been extrapolated from the Canadian Study of Health and Aging conducted in 1991. Based on these estimates, it is projected that there will be approximately 165,000 dementia cases in Ontario in the year 2008, and by 2010 the number of cases will increase by nearly 17% over 2005 levels. By 2020 the number of cases is expected to increase by nearly 55%, due to a rise in the number of people in the age categories with the highest prevalence (85+). With the increase in the aging population, dementia will continue to have a significant economic impact on the Canadian health care system. In 1991, the total costs associated with dementia in Canada were $3.9 billion (Cdn) with $2.18 billion coming from LTC.
Caregivers play a crucial role in the management of individuals with dementia because of the high level of dependency and morbidity associated with the condition. It has been documented that a greater demand is faced by dementia caregivers compared with caregivers of persons with other chronic diseases. The increased burden of caregiving contributes to a host of chronic health problems seen among many informal caregivers of persons with dementia. Much of this burden results from managing the behavioural and psychological symptoms of dementia (BPSD), which have been established as a predictor of institutionalization for elderly patients with dementia.
It is recognized that for some patients with dementia, an LTC facility can provide the most appropriate care; however, many patients move into LTC unnecessarily. For individuals with dementia to remain in the community longer, caregivers require many types of formal and informal support services to alleviate the stress of caregiving. These include both respite care and psychosocial interventions. Psychosocial interventions encompass a broad range of interventions such as psychoeducational interventions, counseling, supportive therapy, and behavioural interventions.
Assuming that 50% of persons with dementia live in the community, a conservative estimate of the number of informal caregivers in Ontario is 82,500. Accounting for the fact that 29% of people with dementia live alone, this leaves a remaining estimate of 58,575 Ontarians providing care for a person with dementia with whom they reside.
Description of Interventions
The 2 main categories of caregiver-directed interventions examined in this review are respite care and psychosocial interventions. Respite care is defined as a break or relief for the caregiver. In most cases, respite is provided in the home, through day programs, or at institutions (usually 30 days or less). Depending on a caregiver’s needs, respite services will vary in delivery and duration. Respite care is carried out by a variety of individuals, including paid staff, volunteers, family, or friends.
Psychosocial interventions encompass a broad range of interventions and have been classified in various ways in the literature. This review will examine educational, behavioural, dementia-specific, supportive, and coping interventions. The analysis focuses on behavioural interventions, that is, those designed to help the caregiver manage BPSD. As described earlier, BPSD are one of the most challenging aspects of caring for a senior with dementia, causing an increase in caregiver burden. The analysis also examines multicomponent interventions, which include at least 2 of the above-mentioned interventions.
Methods of Evidence-Based Analysis
A comprehensive search strategy was used to identify systematic reviews and randomized controlled trials (RCTs) that examined the effectiveness of interventions for caregivers of dementia patients.
Questions
Section 2.1
Are respite care services effective in supporting the well-being of unpaid caregivers of seniors with dementia in the community?
Do respite care services impact on rates of institutionalization of these seniors?
Section 2.2
Which psychosocial interventions are effective in supporting the well-being of unpaid caregivers of seniors with dementia in the community?
Which interventions reduce the risk for institutionalization of seniors with dementia?
Outcomes of Interest
any quantitative measure of caregiver psychological health, including caregiver burden, depression, quality of life, well-being, strain, mastery (taking control of one’s situation), reactivity to behaviour problems, etc.;
rate of institutionalization; and
cost-effectiveness.
Assessment of Quality of Evidence
The quality of the evidence was assessed as High, Moderate, Low, or Very low according to the GRADE methodology and GRADE Working Group. As per GRADE the following definitions apply:
Summary of Findings
Conclusions in Table 1 are drawn from Sections 2.1 and 2.2 of the report.
Summary of Conclusions on Caregiver-Directed Interventions
There is limited evidence from RCTs that respite care is effective in improving outcomes for those caring for seniors with dementia.
There is considerable qualitative evidence of the perceived benefits of respite care.
Respite care is known as one of the key formal support services for alleviating caregiver burden in those caring for dementia patients.
Respite care services need to be tailored to individual caregiver needs as there are vast differences among caregivers and patients with dementia (severity, type of dementia, amount of informal/formal support available, housing situation, etc.)
There is moderate- to high-quality evidence that individual behavioural interventions (≥ 6 sessions), directed towards the caregiver (or combined with the patient) are effective in improving psychological health in dementia caregivers.
There is moderate- to high-quality evidence that multicomponent interventions improve caregiver psychosocial health and may affect rates of institutionalization of dementia patients.
RCT indicates randomized controlled trial.
Patient-Directed Interventions for Dementia
Objective
The section on patient-directed interventions for dementia is broken down into 4 subsections with the following questions:
3.1 Physical Exercise for Seniors with Dementia – Secondary Prevention
What is the effectiveness of physical exercise for the improvement or maintenance of basic activities of daily living (ADLs), such as eating, bathing, toileting, and functional ability, in seniors with mild to moderate dementia?
3.2 Nonpharmacologic and Nonexercise Interventions to Improve Cognitive Functioning in Seniors With Dementia – Secondary Prevention
What is the effectiveness of nonpharmacologic interventions to improve cognitive functioning in seniors with mild to moderate dementia?
3.3 Physical Exercise for Delaying the Onset of Dementia – Primary Prevention
Can exercise decrease the risk of subsequent cognitive decline/dementia?
3.4 Cognitive Interventions for Delaying the Onset of Dementia – Primary Prevention
Does cognitive training decrease the risk of cognitive impairment, deterioration in the performance of basic ADLs or instrumental activities of daily living (IADLs),1 or incidence of dementia in seniors with good cognitive and physical functioning?
Clinical Need: Target Population and Condition
Secondary Prevention2
Exercise
Physical deterioration is linked to dementia. This is thought to be due to reduced muscle mass leading to decreased activity levels and muscle atrophy, increasing the potential for unsafe mobility while performing basic ADLs such as eating, bathing, toileting, and functional ability.
Improved physical conditioning for seniors with dementia may extend their independent mobility and maintain performance of ADL.
Nonpharmacologic and Nonexercise Interventions
Cognitive impairments, including memory problems, are a defining feature of dementia. These impairments can lead to anxiety, depression, and withdrawal from activities. The impact of these cognitive problems on daily activities increases pressure on caregivers.
Cognitive interventions aim to improve these impairments in people with mild to moderate dementia.
Primary Prevention3
Exercise
Various vascular risk factors have been found to contribute to the development of dementia (e.g., hypertension, hypercholesterolemia, diabetes, overweight).
Physical exercise is important in promoting overall and vascular health. However, it is unclear whether physical exercise can decrease the risk of cognitive decline/dementia.
Nonpharmacologic and Nonexercise Interventions
Having more years of education (i.e., a higher cognitive reserve) is associated with a lower prevalence of dementia in crossectional population-based studies and a lower incidence of dementia in cohorts followed longitudinally. However, it is unclear whether cognitive training can increase cognitive reserve or decrease the risk of cognitive impairment, prevent or delay deterioration in the performance of ADLs or IADLs or reduce the incidence of dementia.
Description of Interventions
Physical exercise and nonpharmacologic/nonexercise interventions (e.g., cognitive training) for the primary and secondary prevention of dementia are assessed in this review.
Evidence-Based Analysis Methods
A comprehensive search strategy was used to identify systematic reviews and RCTs that examined the effectiveness, safety and cost effectiveness of exercise and cognitive interventions for the primary and secondary prevention of dementia.
Questions
Section 3.1: What is the effectiveness of physical exercise for the improvement or maintenance of ADLs in seniors with mild to moderate dementia?
Section 3.2: What is the effectiveness of nonpharmacologic/nonexercise interventions to improve cognitive functioning in seniors with mild to moderate dementia?
Section 3.3: Can exercise decrease the risk of subsequent cognitive decline/dementia?
Section 3.4: Does cognitive training decrease the risk of cognitive impairment, prevent or delay deterioration in the performance of ADLs or IADLs, or reduce the incidence of dementia in seniors with good cognitive and physical functioning?
Assessment of Quality of Evidence
The quality of the evidence was assessed as High, Moderate, Low, or Very low according to the GRADE methodology. As per GRADE the following definitions apply:
Summary of Findings
Table 2 summarizes the conclusions from Sections 3.1 through 3.4.
Summary of Conclusions on Patient-Directed Interventions*
Previous systematic review indicated that “cognitive training” is not effective in patients with dementia.
A recent RCT suggests that CST (up to 7 weeks) is effective for improving cognitive function and quality of life in patients with dementia.
Regular leisure time physical activity in midlife is associated with a reduced risk of dementia in later life (mean follow-up 21 years).
Regular physical activity in seniors is associated with a reduced risk of cognitive decline (mean follow-up 2 years).
Regular physical activity in seniors is associated with a reduced risk of dementia (mean follow-up 6–7 years).
Evidence that cognitive training for specific functions (memory, reasoning, and speed of processing) produces improvements in these specific domains.
Limited inconclusive evidence that cognitive training can offset deterioration in the performance of self-reported IADL scores and performance assessments.
1° indicates primary; 2°, secondary; CST, cognitive stimulation therapy; IADL, instrumental activities of daily living; RCT, randomized controlled trial.
Benefit/Risk Analysis
As per the GRADE Working Group, the overall recommendations consider 4 main factors:
the trade-offs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates, and the relative value placed on the outcome;
the quality of the evidence;
translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects such as proximity to a hospital or availability of necessary expertise; and
uncertainty about the baseline risk for the population of interest.
The GRADE Working Group also recommends that incremental costs of health care alternatives should be considered explicitly alongside the expected health benefits and harms. Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 3 reflects the overall trade-off between benefits and harms (adverse events) and incorporates any risk/uncertainty (cost-effectiveness).
Overall Summary Statement of the Benefit and Risk for Patient-Directed Interventions*
Economic Analysis
Budget Impact Analysis of Effective Interventions for Dementia
Caregiver-directed behavioural techniques and patient-directed exercise programs were found to be effective when assessing mild to moderate dementia outcomes in seniors living in the community. Therefore, an annual budget impact was calculated based on eligible seniors in the community with mild and moderate dementia and their respective caregivers who were willing to participate in interventional home sessions. Table 4 describes the annual budget impact for these interventions.
Annual Budget Impact (2008 Canadian Dollars)
Assumed 7% prevalence of dementia aged 65+ in Ontario.
Assumed 8 weekly sessions plus 4 monthly phone calls.
Assumed 12 weekly sessions plus biweekly sessions thereafter (total of 20).
Assumed 2 sessions per week for first 5 weeks. Assumed 90% of seniors in the community with dementia have mild to moderate disease. Assumed 4.5% of seniors 65+ are in long-term care, and the remainder are in the community. Assumed a rate of participation of 60% for both patients and caregivers and of 41% for patient-directed exercise. Assumed 100% compliance since intervention administered at the home. Cost for trained staff from Ministry of Health and Long-Term Care data source. Assumed cost of personal support worker to be equivalent to in-home support. Cost for recreation therapist from Alberta government Website.
Note: This budget impact analysis was calculated for the first year after introducing the interventions from the Ministry of Health and Long-Term Care perspective using prevalence data only. Prevalence estimates are for seniors in the community with mild to moderate dementia and their respective caregivers who are willing to participate in an interventional session administered at the home setting. Incidence and mortality rates were not factored in. Current expenditures in the province are unknown and therefore were not included in the analysis. Numbers may change based on population trends, rate of intervention uptake, trends in current programs in place in the province, and assumptions on costs. The number of patients was based on patients likely to access these interventions in Ontario based on assumptions stated below from the literature. An expert panel confirmed resource consumption.
PMCID: PMC3377513  PMID: 23074509
3.  Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study 
PLoS Medicine  2012;9(2):e1001170.
A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level.
Background
Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings.
Methods and Findings
Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%–4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations.
Conclusions
An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings—in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Currently, more than 35 million people worldwide have dementia, a group of brain disorders characterized by an irreversible decline in memory, problem solving, communication, and other “cognitive” functions. Dementia, the commonest form of which is Alzheimer's disease, mainly affects older people and, because more people than ever are living to a ripe old age, experts estimate that, by 2050, more than 115 million people will have dementia. At present, there is no cure for dementia although drugs can be used to manage some of the symptoms. Risk factors for dementia include physical inactivity, infrequent participation in mentally or socially stimulating activities, and common vascular risk factors such as high blood pressure, diabetes, and smoking. In addition, some studies have reported that mild cognitive impairment (MCI) is associated with an increased risk of dementia. MCI can be seen as an intermediate state between normal cognitive aging (becoming increasingly forgetful) and dementia although many people with MCI never develop dementia, and some types of MCI can be static or self-limiting. Individuals with MCI have cognitive problems that are more severe than those normally seen in people of a similar age but they have no other symptoms of dementia and are able to look after themselves. The best studied form of MCI—amnestic MCI (aMCI)—is characterized by memory problems such as misplacing things and forgetting appointments.
Why Was This Study Done?
Much of the expected increase in dementia will occur in low and middle income countries (LAMICs) because these countries have rapidly aging populations. Given that aMCI is frequently used to define groups of people who may be at risk of developing dementia, it would be useful to know what proportion of community-dwelling older adults in LAMICs have aMCI (the prevalence of aMCI). Such information might help governments plan their future health care and social support needs. In this cross-sectional, population-based study, the researchers estimate the prevalence of aMCI in eight LAMICs using data collected by the 10/66 Dementia Research Group. They also investigate the association of aMCI with sociodemographic factors (for example, age, gender, and education), disability, and neuropsychiatric symptoms such as anxiety, apathy, irritability, and depression. A cross-sectional study collects data on a population at a single time point; the 10/66 Dementia Research Group is building an evidence base to inform the development and implementation of policies for improving the health and social welfare of older people in LAMICs, particularly people with dementia.
What Did the Researchers Do and Find?
In cross-sectional surveys carried out in six Latin American LAMICS, China, and India, more than 15,000 elderly individuals without dementia completed standardized assessments of their mental and physical health and their cognitive function. Interviews with relatives and carers provided further details about the participant's cognitive decline and about neuropsychiatric symptoms. The researchers developed an algorithm (set of formulae) that used the data collected in these surveys to diagnose aMCI in the study participants. Finally, they used statistical methods to analyze the prevalence, distribution, and impact of aMCI in the eight LAMICs. The researchers report that aMCI was associated with disability, anxiety, apathy, and irritability but not with depression and that the prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Other analyses show that, considered across all eight countries, aMCI was modestly associated with being male (men had a slightly higher prevalence of aMCI than women) and with having fewer assets but was not associated with age or education.
What Do These Findings Mean?
These findings suggest that aMCI, as diagnosed using the algorithm developed by the researchers, is consistently associated with higher disability and with neuropsychiatric symptoms in the LAMICs studied but not with most sociodemographic factors. Because prevalidated and standardized measurements were applied consistently in all the countries and a common algorithm was used to define aMCI, these findings also suggest that the prevalence of aMCI varies markedly among LAMIC populations and is similar to or slightly lower than the prevalence most often reported for European and North American populations. Although longitudinal studies are now needed to investigate the extent to which aMCI can be used as risk marker for further cognitive decline and dementia in these settings, the large absolute numbers of older people with aMCI in LAMICs revealed here potentially has important implications for health care and social service planning in these rapidly aging and populous regions of the world.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001170.
Alzheimer's Disease International is the international federation of Alzheimer associations around the world; it provides links to individual associations, information about dementia, and links to three World Alzheimer Reports; information about the 10/66 Dementia Research Group is also available on this web site
The Alzheimer's Society provides information for patients and carers about dementia, including information on MCI and personal stories about living with dementia
The Alzheimer's Association also provides information for patients and carers about dementia and about MCI, and personal stories about dementia
A BBC radio program that includes an interview with a man with MCI is available
MedlinePlus provides links to further resources about MCI and dementia (in English and Spanish)
doi:10.1371/journal.pmed.1001170
PMCID: PMC3274506  PMID: 22346736
4.  Dementia before Death in Ageing Societies— The Promise of Prevention and the Reality 
PLoS Medicine  2006;3(10):e397.
Background
Dementia and severe cognitive impairment are very closely linked to ageing. The longer we live the more likely we are to suffer from these conditions. Given population increases in longevity it is important to understand not only risk and protective factors for dementia and severe cognitive impairment at given ages but also whether protection affects cumulative risk. This can be explored by examining the effect on cumulative risk by time of death of factors found consistently to reduce risk at particular ages, such as education and social status.
Methods and Findings
In this analysis we report the prevalence of dementia and severe cognitive impairment in the year before death in a large population sample. In the Medical Research Council Cognitive Function and Ageing Study (a 10-y population-based cohort study of individuals 65 and over in England and Wales), these prevalences have been estimated by age, sex, social class, and education. Differences have been explored using logistic regression. The overall prevalence of dementia at death was 30%. There was a strong increasing trend for dementia with age from 6% for those aged 65–69 y at time of death to 58% for those aged 95 y and above at time of death. Higher prevalences were seen for severe cognitive impairment, with similar patterns. People with higher education and social class had significantly reduced dementia and severe cognitive impairment before death, but the absolute difference was small (under 10%).
Conclusions
Reducing risk for dementia at a given age will lead to further extension of life, thus cumulative risk (even in populations at lower risk for given ages) remains high. Ageing of populations is likely to result in an increase in the number of people dying with dementia and severe cognitive impairment even in the presence of preventative programmes. Policy development and research for dementia must address the needs of individuals who will continue to experience these conditions before death.
The overall prevalence of dementia at death in this large study was 30%. Ageing of populations is likely to result in an increase in the number of people dying with dementia even in the presence of preventative programmes.
Editors' Summary
Background.
Severe cognitive impairment and its advanced form, dementia, are among the most difficult problems associated with aging in industrialized countries. Age-associated decline in mental functioning is also expected to become more common in developing countries as improvement of conditions that affect health leads to longer life expectancies. Although the risk of cognitive impairment is known to increase with age, the number of people who suffer from loss of mental abilities in the last years of their lives has not been well studied, as such persons are usually reported to have died from other causes. Further, because the very elderly are seldom included in prevention studies, it is not known whether factors found to reduce the risk of developing dementia by a given age will provide protection until the end of life.
Why Was This Study Done?
This study was designed to follow a representative population of aged people over several years to estimate the risk of developing cognitive impairment or dementia near the end of life and to determine whether factors such as education and social class, which may be protective earlier in life, can ultimately prevent decline in mental functioning.
What Did the Researchers Do and Find?
Using standardized assessments of cognitive status, the researchers interviewed people age 65 and over at six sites representing rural and urban areas in the United Kingdom. Interviews were conducted at regular intervals over ten years. Of approximately 12,000 study participants who had died by the time of this report, just over 2,500 had an assessment for dementia within one year before dying. Of this group, those who died between ages 65 and 69 had a 6% chance of dying with dementia, and those who died above age 95 had a 58% chance of dying with dementia. When moderate and severe cognitive impairment were considered together, the rate in people above age 95 reached almost 80%. Women were more likely to develop dementia than men, even after taking into account the fact that women tend to live longer than men. A higher level of education was associated with only a slightly lower risk of dementia before death.
What Do These Findings Mean?
According to these results, as the number of aged persons increases (with improved health care, preventive medicine, and healthier lifestyles), the chances of developing dementia in the last years of life will continue to increase. Factors believed to protect against dementia at earlier times may be of little effect at the end of life. Planning for aging societies must therefore include not only research into treatments and preventive efforts to reduce the impact of dementia at the end of life, but also realistic allocation of resources to support individuals and their caregivers who must deal with the difficulties of cognitive decline.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030397.
Web site of the Medical Research Council Cognitive Function and Ageing Study
Web site of the Alzheimer's Association
Wikipedia entry on dementia (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030397
PMCID: PMC1626550  PMID: 17076551
5.  Epidemiological Pathology of Dementia: Attributable-Risks at Death in the Medical Research Council Cognitive Function and Ageing Study 
PLoS Medicine  2009;6(11):e1000180.
Researchers from the Medical Research Council Cognitive Function and Ageing Neuropathology Study carry out an analysis of brain pathologies contributing to dementia, within a cohort of elderly individuals in the UK who agreed to brain donation.
Background
Dementia drug development aims to modulate pathological processes that cause clinical syndromes. Population data (epidemiological neuropathology) will help to model and predict the potential impact of such therapies on dementia burden in older people. Presently this can only be explored through post mortem findings. We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS).
Methods and Findings
A multicentre, prospective, longitudinal study of older people in the UK was linked to a brain donation programme. Neuropathology of 456 consecutive brain donations assessed degenerative and vascular pathologies. Logistic regression modelling, with bootstrapping and sensitivity analyses, was used to estimate AR at death for dementia for specific pathologies and other factors. The main contributors to AR at death for dementia in MRC CFAS were age (18%), small brain (12%), neocortical neuritic plaques (8%) and neurofibrillary tangles (11%), small vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%).
Conclusions
Such AR estimates cannot be derived from the living population; rather they estimate the relative contribution of specific pathologies to dementia at death. We found that multiple pathologies determine the overall burden of dementia. The impact of therapy targeted to a specific pathology may be profound when the dementia is relatively “pure,” but may be less impressive for the majority with mixed disease, and in terms of the population. These data justify a range of strategies, and combination therapies, to combat the degenerative and vascular determinants of cognitive decline and dementia.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Losing one's belongings and forgetting people's names is often a normal part of aging. But increasing forgetfulness can also be a sign of dementia, a group of symptoms caused by several disorders that affect the structure of the brain. The commonest form of dementia is Alzheimer disease. In this, protein clumps called plaques and neurofibrillary tangles form in the brain and cause its degeneration. Vascular dementia, in which problems with blood circulation deprive parts of the brain of oxygen, is also common. People with dementia have problems with two or more “cognitive” functions—thinking, language, memory, understanding, and judgment. As the disease progresses, they gradually lose their ability to deal with normal daily activities until they need total care, their personality often changes, and they may become agitated or aggressive. Dementia is rare before the age of 65 years but about a quarter of people over 85 years old have dementia. Because more people live to a ripe old age these days, the number of people with dementia is increasing. According to the latest estimates, about 35 million people now have dementia and by 2050, 115 million may have the disorder.
Why Was This Study Done?
There is no cure for dementia but many drugs designed to modulate specific abnormal (pathological) changes in the brain that can cause the symptoms of dementia are being developed. To assess the likely impact of these potentially expensive new therapies, experts need to know what proportion of dementia is associated with each type of brain pathology. Although some brain changes can be detected in living brains with techniques such as computed tomography brain scans, most brain changes can only be studied in brains taken from people after death (post mortem brains). In this study, which is part of the UK Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), the researchers look for associations between dementia in elderly people and pathological changes in their post mortem brains and estimate the attributable-risk (AR) for dementia at death associated with specific pathological features in the brain. That is, they estimate the proportion of dementia directly attributable to each type of pathology.
What Did the Researchers Do and Find?
Nearly 20 years ago, the MRC CFAS interviewed more than 18,000 people aged 65 years or older recruited at six sites in England and Wales to determine their cognitive function and their ability to deal with daily activities. 20% of the participants, which included people with and without cognitive impairment, were then assessed in more detail and invited to donate their brains for post mortem examination. As of 2004, 456 individuals had donated their brains. The dementia status of these donors was established using data from their assessment interviews and death certificates, and from interviews with relatives and carers, and their brains were carefully examined for abnormal changes. The researchers then used statistical methods to estimate the AR for dementia at death associated with various abnormal brain changes. The main contributors to AR for dementia at death included age (18% of dementia at death was attributable to this factor), plaques (8%), and neurofibrillary tangles (11%) in a brain region called the neocortex, small blood vessel disease (12%), and multiple abnormal changes in blood vessels (9%).
What Do These Findings Mean?
These findings suggest that multiple abnormal brain changes determine the overall burden of dementia. Importantly, they also suggest that dementia is often associated with mixed pathological changes—many people with dementia had brain changes consistent with both Alzheimer disease and vascular dementia. Because people with dementia live for variable lengths of time during which the abnormal changes in their brain are likely to alter, it may be difficult to extrapolate these findings to living populations of elderly people. Furthermore, only a small percentage of the MRC CFAS participants have donated their brains so the findings of this study may not apply to the general population. Nevertheless, these findings suggest that the new therapies currently under development may do little to reduce the overall burden of dementia because most people's dementia involves multiple pathologies. Consequently, it may be necessary to develop a range of strategies and combination therapies to deal with the ongoing dementia epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000180.
The US National Institute on Aging provides information for patients and carers about forgetfulness and about Alzheimer disease (in English and Spanish)
The US National Institute of Neurological Disorders and Stroke provides information about dementia (in English and Spanish)
The UK National Health Service Choices Web site also provides detailed information for patients and their carers about dementia and about Alzheimer disease
MedlinePlus provides links to additional resources about dementia and Alzheimer disease (in English and Spanish)
More information about the UK Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) is available
doi:10.1371/journal.pmed.1000180
PMCID: PMC2765638  PMID: 19901977
6.  Computerized Cognitive Training in Cognitively Healthy Older Adults: A Systematic Review and Meta-Analysis of Effect Modifiers 
PLoS Medicine  2014;11(11):e1001756.
Michael Valenzuela and colleagues systematically review and meta-analyze the evidence that computerized cognitive training improves cognitive skills in older adults with normal cognition.
Please see later in the article for the Editors' Summary
Background
New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors.
Methods and Findings
We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I2 = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects.
Conclusions
CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
As we get older, we notice many bodily changes. Our hair goes grey, we develop new aches and pains, and getting out of bed in the morning takes longer than it did when we were young. Our brain may also show signs of aging. It may take us longer to learn new information, we may lose our keys more frequently, and we may forget people's names. Cognitive decline—developing worsened thinking, language, memory, understanding, and judgment—can be a normal part of aging, but it can also be an early sign of dementia, a group of brain disorders characterized by a severe, irreversible decline in cognitive functions. We know that age-related physical decline can be attenuated by keeping physically active; similarly, engaging in activities that stimulate the brain throughout life is thought to enhance cognition in later life and reduce the risk of age-related cognitive decline and dementia. Thus, having an active social life and doing challenging activities that stimulate both the brain and the body may help to stave off cognitive decline.
Why Was This Study Done?
“Brain training” may be another way of keeping mentally fit. The sale of computerized cognitive training (CCT) packages, which provide standardized, cognitively challenging tasks designed to “exercise” various cognitive functions, is a lucrative and expanding business. But does CCT work? Given the rising global incidence of dementia, effective interventions that attenuate age-related cognitive decline are urgently needed. However, the impact of CCT on cognitive performance in older adults is unclear, and little is known about what makes a good CCT package. In this systematic review and meta-analysis, the researchers assess whether CCT programs improve cognitive test performance in cognitively healthy older adults and identify the aspects of cognition (cognitive domains) that are responsive to CCT, and the CCT design features that are most important in improving cognitive performance. A systematic review uses pre-defined criteria to identify all the research on a given topic; meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 51 trials that investigated the effects of more than four hours of CCT on nearly 5,000 cognitively healthy older adults by measuring several cognitive functions before and after CCT. Meta-analysis of these studies indicated that the overall effect size for CCT (compared to control individuals who did not participate in CCT) was small but statistically significant. An effect size quantifies the difference between two groups; a statistically significant result is a result that is unlikely to have occurred by chance. So, the meta-analysis suggests that CCT slightly increased overall cognitive function. Notably, CCT also had small to moderate significant effects on individual cognitive functions. For example, some CCT slightly improved nonverbal memory (the ability to remember visual images) and working memory (the ability to remember recent events; short-term memory). However, CCT had no significant effect on executive functions (cognitive processes involved in planning and judgment) or attention (selective concentration on one aspect of the environment). The design of CCT used in the different studies varied considerably, and “moderator” analyses revealed that home-based CCT was not effective, whereas center-based CCT was effective, and that training sessions undertaken more than three times a week were not effective. There was also some weak evidence suggesting that CCT sessions lasting less than 30 minutes may be ineffective. Finally, there was no evidence for the effectiveness of working memory training by itself (for example, programs that ask individuals to recall series of letters).
What Do These Findings Mean?
These findings suggest that CCT produces small improvements in cognitive performance in cognitively healthy older adults but that the efficacy of CCT varies across cognitive domains and is largely determined by design aspects of CCT. The most important result was that “do-it-yourself” CCT at home did not produce improvements. Rather, the small improvements seen were in individuals supervised by a trainer in a center and undergoing sessions 1–3 times a week. Because only cognitively healthy older adults were enrolled in the studies considered in this systematic review and meta-analysis, these findings do not necessarily apply to cognitively impaired individuals. Moreover, because all the included studies measured cognitive function immediately after CCT, these findings provide no information about the durability of the effects of CCT or about how the effects of CCT on cognitive function translate into real-life outcomes for individuals such as independence and the long-term risk of dementia. The researchers call, therefore, for additional research into CCT, an intervention that might help to attenuate age-related cognitive decline and improve the quality of life for older individuals.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001756.
This study is further discussed in a PLOS Medicine Perspective by Druin Burch
The US National Institute on Aging provides information for patients and carers about age-related forgetfulness, about memory and cognitive health, and about dementia (in English and Spanish)
The UK National Health Service Choices website also provides information about dementia and about memory loss
MedlinePlus provides links to additional resources about memory, mild cognitive impairment, and dementia (in English and Spanish)
doi:10.1371/journal.pmed.1001756
PMCID: PMC4236015  PMID: 25405755
7.  Dementia and Its Implications for Public Health 
Preventing Chronic Disease  2006;3(2):A34.
Introduction
With the aging of the U.S. population, a better understanding of the presentation and impact of dementia is essential to the future of public health. Dementia refers not to a single disorder but to a number of syndromes characterized by diverse behavioral, cognitive, and emotional impairments. Because dementia is costly in terms of both personal suffering and economic loss, an understanding of its prevalence, risk factors, and potential interventions is emerging as an increasingly important facet of public health and health care delivery. Recent advances in the understanding of its presentation, course, and relevant interventions have taken place.
Methods
We identified articles for review primarily by conducting a Medline search using the subject headings dementia, mild cognitive impairment, Alzheimer's disease, vascular dementia, frontotemporal dementia, and Lewy body dementia. Other relevant studies were elicited through a Medline search using the subject headings mental disorders and stigma.
Results
Dementia represents a diverse category of syndromes characterized by deficits in memory, cognitive function, and behavior. Symptoms associated with dementia appear to be distributed along a continuum, with even subsyndromal presentations affecting the health of older adults and meriting intervention. To promote cognitive functioning and independence among older adults, public health interventions need to facilitate both early detection and treatment of dementia. The availability of adult day care and respite services is important in maintaining the health and quality of life of individuals caring for older adults with dementia. Recent advances in the treatment of dementia may slow the course of cognitive decline, thereby enhancing the quality of life of older individuals as well as decreasing costs associated with institutional care.
Conclusion
Despite the growing availability of pharmacologic and psychosocial interventions that are potentially helpful to people with dementia and their caregivers, the majority of older adults with dementia do not receive appropriate treatment. With the aging of the U.S. population, efforts to foster recognition of dementia and its treatments and to destigmatize them are emerging as an increasingly important facet of public health intervention.
PMCID: PMC1563968  PMID: 16539775
8.  First Diagnosis and Management of Incontinence in Older People with and without Dementia in Primary Care: A Cohort Study Using The Health Improvement Network Primary Care Database 
PLoS Medicine  2013;10(8):e1001505.
Robert Grant and colleagues used the British THIN primary care database to determine rates of first diagnosis of urinary and faecal incontinence among people aged 60–89 with dementia compared with those without dementia, and the use of medication or indwelling catheters for urinary incontinence in those with and without dementia.
Please see later in the article for the Editors' Summary
Background
Dementia is one of the most disabling and burdensome diseases. Incontinence in people with dementia is distressing, adds to carer burden, and influences decisions to relocate people to care homes. Successful and safe management of incontinence in people with dementia presents additional challenges. The aim of this study was to investigate the rates of first diagnosis in primary care of urinary and faecal incontinence among people aged 60–89 with dementia, and the use of medication or indwelling catheters for urinary incontinence.
Methods and Findings
We extracted data on 54,816 people aged 60–89 with dementia and an age-gender stratified sample of 205,795 people without dementia from 2001 to 2010 from The Health Improvement Network (THIN), a United Kingdom primary care database. THIN includes data on patients and primary care consultations but does not identify care home residents. Rate ratios were adjusted for age, sex, and co-morbidity using multilevel Poisson regression.
The rates of first diagnosis per 1,000 person-years at risk (95% confidence interval) for urinary incontinence in the dementia cohort, among men and women, respectively, were 42.3 (40.9–43.8) and 33.5 (32.6–34.5). In the non-dementia cohort, the rates were 19.8 (19.4–20.3) and 18.6 (18.2–18.9). The rates of first diagnosis for faecal incontinence in the dementia cohort were 11.1 (10.4–11.9) and 10.1 (9.6–10.6). In the non-dementia cohort, the rates were 3.1 (2.9–3.3) and 3.6 (3.5–3.8).
The adjusted rate ratio for first diagnosis of urinary incontinence was 3.2 (2.7–3.7) in men and 2.7 (2.3–3.2) in women, and for faecal incontinence was 6.0 (5.1–7.0) in men and 4.5 (3.8–5.2) in women. The adjusted rate ratio for pharmacological treatment of urinary incontinence was 2.2 (1.4–3.7) for both genders, and for indwelling urinary catheters was 1.6 (1.3–1.9) in men and 2.3 (1.9–2.8) in women.
Conclusions
Compared with those without a dementia diagnosis, those with a dementia diagnosis have approximately three times the rate of diagnosis of urinary incontinence, and more than four times the rate of faecal incontinence, in UK primary care. The clinical management of urinary incontinence in people with dementia with medication and particularly the increased use of catheters is concerning and requires further investigation.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Globally, more than 35 million people have dementia, brain disorders that are characterized by an irreversible decline in cognitive functions such as language and memory. Alzheimer's disease and other forms of dementia mainly affect older people and, because people are living longer than ever, experts estimate that by 2050 more than 115 million people will have dementia. The earliest sign of dementia is usually increasing forgetfulness but, as the disease progresses, people gradually lose their ability to deal with normal daily activities such as dressing, they may become anxious or aggressive, and they may lose control of their bladder (urinary incontinence), bowels (bowel or fecal incontinence), and other physical functions. As a result, people with dementia require increasing amounts of care as the disease progresses. Relatives and other unpaid carers provide much of this care—two-thirds of people with dementia are cared for at home. However, many people with dementia end their days in a care or nursing home.
Why Was This Study Done?
Incontinence in people with dementia is distressing for the person with dementia and for their carers and often influences decisions to move individuals into care homes. However, little is known about the diagnosis and treatment of urinary and/or fecal incontinence among people with dementia living at home. This information is needed to help policymakers commission the services required for this section of society and insurers recognize the needs such patients have, as well as helping to raise clinicians' awareness of the issue. In this cohort study (an investigation that compares outcomes in groups of people with different characteristics), the researchers use data routinely collected from general practices (primary care) in the UK to determine the rate of first diagnosis of urinary and fecal incontinence in elderly patients with and without dementia and to find out whether a diagnosis of dementia affects the rate of use of drugs or of indwelling urinary catheters (tubes inserted into the bladder to drain urine from the body) for the treatment of urinary incontinence.
What Did the Researchers Do and Find?
The researchers extracted data collected between 2001 and 2010 on incontinence for nearly 55,000 people aged 60–89 with a diagnosis of dementia (the dementia cohort) and for more than 200,000 individuals without a diagnosis of dementia (the non-dementia cohort) from The Health Improvement Network (THIN) primary care database, which includes anonymized consultation records from nearly 500 UK general practices. In the dementia cohort, the rates of first diagnosis of urinary incontinence were 42.3 and 33.5 per 1,000 person-years at risk among men and women, respectively. In the non-dementia cohort, the corresponding rates were 19.8 and 18.6. The rates of first diagnosis of fecal incontinence were 11.1 and 10.1 in the dementia cohort, and 3.1 and 3.6 in the non-dementia cohort among men and women, respectively. After adjusting for age, sex and other diseases, the adjusted rate ratio for the first diagnosis of urinary incontinence in people with dementia compared to people without dementia was 3.2 in men and 2.7 in women; for fecal incontinence, it was 6.0 in men and 4.5 in women; the adjusted rate ratio was 2.2 for both men and women for drug treatment of urinary incontinence and 1.6 in men and 2.3 in women for use of indwelling urinary catheters.
What Do These Findings Mean?
These findings indicate that, in primary care in the UK, dementia is associated with a three-fold higher rate of diagnosis of urinary incontinence and a greater than four-fold higher rate of diagnosis of fecal incontinence. Moreover, the authors suggest that some aspects of clinical management of urinary continence vary between people with and without dementia. In particular, the use of indwelling urinary catheters appears to be more common among people with dementia than among people without dementia, increasing the risk of infection. Thus, health care practitioners providing care for people with dementia may be prioritizing ease of management over risk avoidance, a possibility that requires further investigation. Although the accuracy of these findings is limited by certain aspects of the study design (for example, the THIN database does not identify which patients are living in care homes), they nevertheless suggest that policymakers and insurers involved in planning and providing services for people with dementia living at home need to provide high levels of help with incontinence, including the provision of advice and support for carers.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001505.
The UK not-for-profit organization Alzheimers Society provides information for patients and carers about dementia, including information on coping with incontinence and personal stories about living with dementia
The US not-for-profit organization Alzheimers Association also provides information for patients and carers about dementia and about incontinence, and personal stories about dementia
The UK National Health Service Choices website provides information (including personal stories) about dementia, urinary incontinence, and bowel incontinence
MedlinePlus provides links to further resources about dementia, urinary incontinence and fecal incontinence (in English and Spanish)
The International Continence Society and the International Consultation on Urological Diseases provide independent advice on products to manage incontinence
More information about the THIN database is available
doi:10.1371/journal.pmed.1001505
PMCID: PMC3754889  PMID: 24015113
9.  Psychosocial Factors That Shape Patient and Carer Experiences of Dementia Diagnosis and Treatment: A Systematic Review of Qualitative Studies 
PLoS Medicine  2012;9(10):e1001331.
A systematic review of qualitative studies conducted by Frances Bunn and colleagues identifies and describes the experiences of patients and caregivers on receiving and adapting to a diagnosis of dementia.
Background
Early diagnosis and intervention for people with dementia is increasingly considered a priority, but practitioners are concerned with the effects of earlier diagnosis and interventions on patients and caregivers. This systematic review evaluates the qualitative evidence about how people accommodate and adapt to the diagnosis of dementia and its immediate consequences, to guide practice.
Methods and Findings
We systematically reviewed qualitative studies exploring experiences of community-dwelling individuals with dementia, and their carers, around diagnosis and the transition to becoming a person with dementia. We searched PubMed, PsychINFO, Embase, CINAHL, and the British Nursing Index (all searched in May 2010 with no date restrictions; PubMed search updated in February 2012), checked reference lists, and undertook citation searches in PubMed and Google Scholar (ongoing to September 2011). We used thematic synthesis to identify key themes, commonalities, barriers to earlier diagnosis, and support identified as helpful. We identified 126 papers reporting 102 studies including a total of 3,095 participants. Three overarching themes emerged from our analysis: (1) pathways through diagnosis, including its impact on identity, roles, and relationships; (2) resolving conflicts to accommodate a diagnosis, including the acceptability of support, focusing on the present or the future, and the use or avoidance of knowledge; and (3) strategies and support to minimise the impact of dementia. Consistent barriers to diagnosis include stigma, normalisation of symptoms, and lack of knowledge. Studies report a lack of specialist support particularly post-diagnosis.
Conclusions
There is an extensive body of qualitative literature on the experiences of community-dwelling individuals with dementia on receiving and adapting to a diagnosis of dementia. We present a thematic analysis that could be useful to professionals working with people with dementia. We suggest that research emphasis should shift towards the development and evaluation of interventions, particularly those providing support after diagnosis.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Dementia is a decline in mental ability severe enough to interfere with daily life. Alzheimer disease is the most common type of dementia. People with dementia usually have problems with two or more cognitive functions—thinking, language, memory, understanding, and judgment. Dementia is rare before the age of 65, but about a quarter of people over 85 have dementia. Because more people live longer these days, the number of patients with dementia is increasing. It is estimated that today between 40 and 50 million people live with dementia worldwide. By 2050, this number is expected to triple.
One way to study what dementia means to patients and their carers (most often spouses or other family members) is through qualitative research. Qualitative research aims to develop an in-depth understanding of individuals' experiences and behavior, as well as the reasons for their feelings and actions. In qualitative studies, researchers interview patients, their families, and doctors. When the studies are published, they usually contain direct quotations from interviews as well as summaries by the scientists who designed the interviews and analyzed the responses.
Why Was This Study Done?
This study was done to better understand the experiences and attitudes of patients and their carers surrounding dementia diagnosis. It focused on patients who lived and were cared for within the community (as opposed to people living in senior care facilities or other institutions). Most cases of dementia are progressive, meaning symptoms get worse over time. Diagnosis often happens at an advanced stage of the disease, and some patients never receive a formal diagnosis. This could have many possible reasons, including unawareness or denial of symptoms by patients and people close to them. The study was also trying to understand barriers to early diagnosis and what type of support is useful for newly diagnosed patients and carers.
What Did the Researchers Do and Find?
The researchers conducted a systematic search for published qualitative research studies that reported on the experience, beliefs, feelings, and attitudes surrounding dementia diagnosis. They identified and reviewed 102 such studies. Among the quotations and summaries of the individual studies, they looked for prominent and recurring themes. They also compared and contrasted the respective experiences of patients and carers.
Overall, they found that the complexity and variety of responses to a diagnosis of dementia means that making the diagnosis and conveying it to patients and carers is challenging. Negative connotations associated with dementia, inconsistent symptoms, and not knowing enough about the signs and symptoms were commonly reported barriers to early dementia diagnosis. It was often the carer who initiated the search for help from a doctor, and among patients, willingness and readiness to receive a diagnosis varied. Being told one had dementia had a big impact on a patient's identity and often caused feelings of loss, anger, fear, and frustration. Spouses had to adjust to increasingly unequal relationships and the transition to a role as carer. The strain associated with this often caused health problems in the carers as well. On the other hand, studies examining the experience of couples often reported that they found ways to continue working together as a team.
Adjusting to a dementia diagnosis is a complex process. Initially, most patients and carers experienced conflicts, for example, between autonomy and safety, between recognizing the need for help but reluctance to accept it, or between living in the present and dealing with anxiety about and preparing for the future. As these were resolved and as the disease progressed, the attitudes of patients and carers towards dementia often became more balanced and accepting. Many patients and their families adopted strategies to cope with the impact of dementia on their lives in order to manage the disease and maintain some sort of normal life. These included practical strategies involving reminders, social strategies such as relying on family support, and emotional strategies such as using humor. At some point many patients and carers reported that they were able to adopt positive mindsets and incorporate dementia in their lives.
The studies also pointed to an urgent need for support from outside the family, both right after diagnosis and subsequently. General practitioners and family physicians have important roles in helping patients and carers to get access to information, social and psychological support, and community care. The need for information was reported to be ongoing and varied, and meeting it required a variety of sources and formats. Key needs for patients and carers mentioned in the studies include information on financial aids and entitlements early on, and continued access to supportive professionals and specialists.
What Do These Findings Mean?
Qualitative studies to date on how patients and carers respond to a diagnosis of dementia provide a fairly detailed picture of their experiences. The summary provided here should help professionals to understand better the challenges patients and carers face around the time of diagnosis as well as their immediate and evolving needs. The results also suggest that future research should focus on the development and evaluation of ways to meet those needs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001331.
Wikipedia has pages on dementia and qualitative research (note that Wikipedia is a free online encyclopedia that anyone can edit)
Alzheimer Europe, an umbrella organization of 34 Alzheimer associations from 30 countries across Europe, has a page on the different approaches to research
The UK Department of Health has pages on dementia, including guidelines for carers of people with dementia
MedlinePlus also has information about dementia
doi:10.1371/journal.pmed.1001331
PMCID: PMC3484131  PMID: 23118618
10.  Dementia 
Clinical Evidence  2010;2010:1001.
Introduction
Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or vascular)? What are the effects of treatments on behavioural and psychological symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), antidepressants (clomipramine, fluoxetine, imipramine, sertraline), antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy, benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT), cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and statins.
Key Points
Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired.
Median life expectancy for people with Alzheimer's and Lewy body dementia is about 6 years after diagnosis, although many people may live far longer.
RCTs of dementia are often not representative of all people with dementia; most are 6 months or less, not in primary care, and most RCTs are in people with Alzheimer's disease. There are fewer RCTs in people with vascular dementia, and fewer still in people with Lewy body dementia.
Cognitive symptoms of dementia can be improved by acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine). Acetylcholinesterase inhibitors seem to improve cognitive function, global state, and activities of daily living scores compared with placebo at 26 weeks in people with Alzheimer's disease.However, they may be associated with an increase in adverse effects, particularly GI symptoms (anorexia, nausea, vomiting, or diarrhoea).
We don't know whether cognitive stimulation, music therapy, reminiscence therapy, omega 3 fish oil, statins, or NSAIDs are effective at improving cognitive outcomes in people with cognitive symptoms of dementia, as we found insufficient evidence.
In people with cognitive symptoms, memantine may improve global state and activities of daily living scores in people with moderate to severe Alzheimer's disease over 24 to 28 weeks, but we don't know about these in mild to moderate Alzheimer's disease. Although memantine is associated with a statistically significant increase in cognition scores in some population groups, the clinical importance of these results is unclear.
Ginkgo biloba is unlikely to improve cognitive function in people with Alzheimer's disease or vascular dementia. However, evidence is of poor quality so this conclusion should be interpreted with caution.
Acetylcholinesterase inhibitors may marginally improve neuropsychiatric symptoms compared with placebo in people with behavioural and psychological symptoms of dementia, but they are also associated with adverse effects.
Antidepressants (clomipramine, fluoxetine, imipramine, sertraline) may improve depressive symptoms compared with placebo in people with Alzheimer's disease associated with depression. However, RCTs were small and short term, and adverse effects were sparsely reported.
Memantine may be associated with a small improvement in neuropsychiatric symptoms compared with placebo in people with behavioural and psychological symptoms of dementia, but it is also associated with adverse effects.
We don't know whether diazepam, lorazepam, aromatherapy, CBT, exercise, carbamazepine, or sodium valproate/valproic acid are effective at improving neuropsychiatric symptoms in people with behavioural and psychological symptoms of dementia, as we found insufficient evidence.
Some antipsychotics may improve neuropsychiatric symptoms or aggression in people with behavioural and psychological symptoms of dementia, but antipsychotics are also associated with an increase risk of severe adverse events such as stroke, TIA, or death.
CAUTION: Regulatory bodies have issued alerts that both conventional and atypical antipsychotics are associated with an increased risk of death in elderly people treated for dementia-related psychosis.
PMCID: PMC2907611  PMID: 21726471
11.  A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial)  
PLoS Medicine  2008;5(4):e76.
Background
There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.
Methods and Findings
Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.
Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.
Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.
Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.
Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).
Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) −0.4 (95% confidence interval [CI] −6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) −2.4 (95% CI −8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI ≥ 15 benefited on neuropsychiatric symptoms from continuing treatment.
Conclusions
For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.
Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).
In a randomized trial of patients with dementia, Clive Ballard and colleagues show that withdrawal of neuroleptics had no overall detrimental effect, and by some measures improved, functional and cognitive status.
Editors' Summary
Background
The number of people with dementia (currently 25 million worldwide) is expected to increase by 5 million each year. The risk of dementia, including Alzheimer disease, increases sharply with age: Alzheimer's Disease International estimates that 1.4% of people 65–69 have dementia, whereas almost a full quarter of those over the age of 85 years are affected. Almost all older dementia patients will experience, along with the cognitive and functional decline typical of the illness, some neuropsychiatric symptoms. These symptoms can include agitation, aggression, and psychosis, and are often devastating for the older patient and his or her family and caregiver. Managing these symptoms is often a prime concern for health-care providers and families. Neuroleptics (sometimes called antipsychotics) are the class of drugs often used to manage or control neuropsychiatric problems, but there have been questions about their safety and appropriateness. Safety concerns involve risk of stroke, parkinsonism, sedation, edema, and chest infections but also include a worsening of cognitive decline with prolonged use of neuroleptics.
Why Was the Study Done?
Previous studies on the effectiveness and safety of neuroleptics in older people have been short term. Ballard and colleagues wanted to study over a longer period of time the impact of neuroleptic drugs on elderly patients with dementia. Specifically, they wanted to know if being on a neuroleptic was associated with more cognitive decline than coming off the drug. They also wanted to investigate whether discontinuing the drug exacerbated any neuropsychiatric symptoms, Parkinson disease-like symptoms, or other functional, language, and cognition difficulties frequently associated with dementia.
What Did the Researchers Do and Find?
The researchers recruited older patients with Alzheimer disease from across England who had been on neuroleptics for at least three months. They randomised patients to one of two groups: the first group continued taking the same neuroleptic at the same dosage level while the second group was switched to an identical-looking placebo. The researchers assessed the patients' cognitive status and neuropsychiatric symptoms upon their entry into the study. Six and 12 months later the researchers assessed any cognitive decline and the level of neuropsychiatric and other problems that patients were experiencing.
At both 6 and 12 months, the researchers found that there were no differences between the two groups (continued treatment and placebo) in terms of cognitive decline. The placebo group may have had less cognitive decline, but this was not statistically significant. They also found no overall differences between the two groups in the change in the number of neuropsychiatric symptoms over these time periods. Patients with severe neuropsychiatric problems at the outset of the trial did better on continued neuroleptic therapy, but this advantage was not statistically significant. There was a significant decline on the verbal fluency language tests among the patients who continued on their neuroleptic.
What Do these Findings Mean?
The researchers report perhaps the first trial of this duration on continued versus withdrawn neuroleptic treatment among older dementia patients. The findings do not indicate any benefit of continuing neuroleptic therapies in older patients on either cognitive or neuropsychiatric outcomes. The researchers conclude that neuroleptics, with their known safety issues, should not be used as first-line treatment to manage problems such as agitation or aggression. For older dementia patients whose neuropsychiatric symptoms are not remedied by nonpharmaceutical treatments, the researchers advise caution. More studies are urgently needed to find better solutions to help older patients with dementia who have agitation, aggression, and psychosis.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050076.
Alzheimer's Disease International is an umbrella organisation of organisations worldwide
The Alzheimer's Research Trust in the UK is a charity funding research to cure or prevent dementias
The US National Institutes of Aging has information on Alzheimer Disease in English and Spanish
Two governmental regulatory agencies—the Medicines and Healthcare Products Regulatory Agency in the UK and the Food and Drug Administration in the US—offer information about antipsychotics in people with dementia
doi:10.1371/journal.pmed.0050076
PMCID: PMC2276521  PMID: 18384230
12.  The dementia and disability project in Thai elderly: rational, design, methodology and early results 
BMC Neurology  2013;13:3.
Background
A strong inverse relationship of functional limitation and socioeconomic status has been established in western ageing society. Functional limitation can be related to chronic diseases, disuse, cognitive decline, and ageing. Among chronic diseases in the Thai population, cerebrovascular diseases, diabetes, and arthritis are common. These factors are known to contribute to disability and poor quality of life in the elder population. Neuropsychiatric problems, cognitive decline, dementia, and cultural issues in elderly people also can alter the quality of life of the elderly.
Methods
The Dementia and Disability Project in Thai Elderly (DDP) aims at comprehensively assessing community dwelling Thai elderly to understand the relationship between disability and motor function, neuropsychiatric symptoms, cognitive function, and chronic diseases. The DDP is the first study to look at the prevalence and etiology of dementia and of mild cognitive impairment (MCI) in Thai elders and to explore the relationship of cognition, disability, small vessel diseases and cortical degeneration with neuroimaging in Thai elderly people. 1998 Thai elders were screened in 2004–2006 and diagnosed as having MCI or dementia. 223 elders with MCI or dementia and cognitively normal elderly had brain magnetic resonance imaging (MRI) or at baseline. 319 elders from the 3 groups had blood tests to investigate the risks and possible etiologies of dementia including genotyping at baseline.
Results
The mean age of elders in this study is 69.51(SD=6.71, min=60, max=95) years. 689(34.9%) are men and 1284(65.1%) are women. Mean body weight was 58.36(SD=11.20) kgs. The regression model reveals that performance on gait and balance and serum triglyceride predicts activity of daily living performance (adjusted r2 = 0.280, f=2.644, p=0.003). The majority of abnormal gait in Thai elders was lower level gait disturbance. Only 1.5% (29/1952) had highest level gait disorders. 39.5% of 1964 subjects were free of chronic diseases. Treatment gap (indicating those who have untreated or inadequate treatment) of diabetes mellitus and hypertension in Thai elders in this study was 37% and 55.5% respectively. 62.6% of Thai elders have ApoE3E3 allele. Prevalence of positive ApoE4 gene in this study is 22.85%. 38.6% of Thai elders who had MRI brain study have moderate to severe white matter lesions.
Conclusion
The large and comprehensive set of measurements in DDP allows a wide-ranging explanation of the functional and clinical features to be investigated in relation to white matter lesions or cortical atrophy of the brain in Thai elderly population. An almost 2 year follow up was made available to those with MCI and dementia and some of the cognitively normal elderly. The longitudinal design will provide great understanding of the possible contributors to disability in the elderly and to the progression of cognitive decline in Thai elders.
doi:10.1186/1471-2377-13-3
PMCID: PMC3552988  PMID: 23305293
Mild cognitive impairment; Dementia; Alzheimer disease; Disability; White matter lesions; Thailand
13.  Cholinesterase Inhibitors in Mild Cognitive Impairment: A Systematic Review of Randomised Trials 
PLoS Medicine  2007;4(11):e338.
Background
Mild cognitive impairment (MCI) refers to a transitional zone between normal ageing and dementia. Despite the uncertainty regarding the definition of MCI as a clinical entity, clinical trials have been conducted in the attempt to study the role of cholinesterase inhibitors (ChEIs) currently approved for symptomatic treatment of mild to moderate Alzheimer disease (AD), in preventing progression from MCI to AD. The objective of this review is to assess the effects of ChEIs (donepezil, rivastigmine, and galantamine) in delaying the conversion from MCI to Alzheimer disease or dementia.
Methods and Findings
The terms “donepezil”, “rivastigmine”, “galantamine”, and “mild cognitive impairment” and their variants, synonyms, and acronyms were used as search terms in four electronic databases (MEDLINE, EMBASE, Cochrane, PsycINFO) and three registers: the Cochrane Collaboration Trial Register, Current Controlled Trials, and ClinicalTrials.gov. Published and unpublished studies were included if they were randomized clinical trials published (or described) in English and conducted among persons who had received a diagnosis of MCI and/or abnormal memory function documented by a neuropsychological assessment. A standardized data extraction form was used. The reporting quality was assessed using the Jadad scale. Three published and five unpublished trials met the inclusion criteria (three on donepezil, two on rivastigmine, and three on galantamine). Enrolment criteria differed among the trials, so the study populations were not homogeneous. The duration of the trials ranged from 24 wk to 3 y. No significant differences emerged in the probability of conversion from MCI to AD or dementia between the treated groups and the placebo groups. The rate of conversion ranged from 13% (over 2 y) to 25% (over 3 y) among treated patients, and from 18% (over 2 y) to 28% (over 3 y) among those in the placebo groups. Only for two studies was it possible to derive point estimates of the relative risk of conversion: 0.85 (95% confidence interval 0.64–1.12), and 0.84 (0.57–1.25). Statistically significant differences emerged for three secondary end points. However, when adjusting for multiple comparisons, only one difference remained significant (i.e., the rate of atrophy in the whole brain).
Conclusions
The use of ChEIs in MCI was not associated with any delay in the onset of AD or dementia. Moreover, the safety profile showed that the risks associated with ChEIs are not negligible. The uncertainty regarding MCI as a clinical entity raises the question as to the scientific validity of these trials.
A systematic review of trials of cholinesterase inhibitors for preventing transition of mild cognitive impairment (MCI) to dementia, conducted by Roberto Raschetti and colleagues, found no difference between treatment and control groups and concluded that uncertainty regarding the definition of MCI casts doubts on the validity of such trials.
Editors' Summary
Background.
Worldwide, more than 24 million people have dementia, a group of brain disorders characterized by an irreversible decline in memory, problem solving, communication, and other “cognitive” functions. The commonest form of dementia is Alzheimer disease (AD). The risk of developing AD increases with age—AD is rare in people younger than 65 but about half of people over 85 years old have it. The earliest symptom of AD is usually difficulty in remembering new information. As the disease progresses, patients may become confused and have problems expressing themselves. Their behavior and personality can also change. In advanced AD, patients need help with daily activities like dressing and eating, and eventually lose their ability to recognize relatives and to communicate. There is no cure for AD but a class of drugs called “cholinesterase inhibitors” can sometimes temporarily slow the worsening of symptoms. Three cholinesterase inhibitors—donepezil, rivastigmine, and galantamine—are currently approved for use in mild-to-moderate AD.
Why Was This Study Done?
Some experts have questioned the efficacy of cholinesterase inhibitors in AD, but other experts and patient support groups have called for these drugs to be given to patients with a condition called mild cognitive impairment (MCI) as well as to those with mild AD. People with MCI have memory problems that are more severe than those normally seen in people of their age but no other symptoms of dementia. They are thought to have an increased risk of developing AD, but it is not known whether everyone with MCI eventually develops AD, and there is no standardized way to diagnose MCI. Despite these uncertainties, several clinical trials have investigated whether cholinesterase inhibitors prevent progression from MCI to AD. In this study, the researchers have assessed whether the results of these trials provide any evidence that cholinesterase inhibitors can prevent MCI progressing to AD.
What Did the Researchers Do and Find?
The researchers conducted a systematic review of the medical literature to find trials that had addressed this issue, which met criteria that they had defined clearly in advance of their search. They identified three published and five unpublished randomized controlled trials (studies in which patients randomly receive the test drug or an inactive placebo) that investigated the effect of cholinesterase inhibitors on the progression of MCI. The researchers obtained the results of six of these trials—four examined the effect of cholinesterase inhibitors on the conversion of MCI to clinically diagnosed AD or dementia (the primary end point); all six examined the effect of the drugs on several secondary end points (for example, individual aspects of cognitive function). None of the drugs produced a statistically significant difference (a difference that is unlikely to have happened by chance) in the probability of progression from MCI to AD. The only statistically significant secondary end point after adjustment for multiple comparisons (when many outcomes are considered, false positive results can occur unless specific mathematical techniques are used to prevent this problem) was a decrease in the rate of brain shrinkage associated with galantamine treatment. More patients treated with cholinesterase inhibitors dropped out of trials because of adverse effects than patients given placebo. Finally, in the one trial that reported all causes of deaths, one participant who received placebo and six who received galantamine died.
What Do These Findings Mean?
These findings suggest that the use of cholinesterase inhibitors is not associated with any delay in the onset of clinically diagnosed AD or dementia in people with MCI. They also show that the use of these drugs has no effect on most surrogate (substitute) indicators of AD but that the risks associated with their use are not negligible. However, because MCI has not yet been clearly defined as a clinical condition that precedes dementia, some (even many) of the patients enrolled into the trials that the researchers assessed may not actually have had MCI. Thus, further clinical trials are needed to clarify whether cholinesterase inhibitors can delay the progression of MCI to dementia, but these additional trials should not be done until the diagnosis of MCI has been standardized.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040338.
An essay by Matthews and colleagues, in the October 2007 issue of PLoS Medicine, discusses how mild cognitive impairment is currently diagnosed
The US Alzheimer's Association provides information about all aspects of Alzheimer disease, including fact sheets on treatments for Alzheimer disease and on mild cognitive impairment
The UK Alzheimer's Society provides information for patients and caregivers on all aspects of dementia, including drug treatments and mild cognitive impairment
The UK charity DIPEx provides short video clips of personal experiences of care givers of people with dementia
doi:10.1371/journal.pmed.0040338
PMCID: PMC2082649  PMID: 18044984
14.  Alzheimer’s Disease and Age-Related Memory Decline (Preclinical) 
An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function.
doi:10.1016/j.pbb.2011.02.002
PMCID: PMC3113643  PMID: 21315756
cognition; drug development; pro-cognitive; neurotransmitter receptors; Mild Cognitive Impairment; dementia
15.  Dementia 
Clinical Evidence  2012;2012:1001.
Introduction
Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or vascular)? What are the effects of treatments on behavioural and psychological symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 49 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), antidepressants (clomipramine, fluoxetine, imipramine, sertraline), antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy, benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT), cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and statins.
Key Points
Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired.
Median life expectancy for people with Alzheimer's and Lewy body dementia is about 6 years after diagnosis, although many people may live far longer.
RCTs of dementia are often not representative of all people with dementia; most are of 6 months' duration or less, not in primary care, and in people with Alzheimer's disease. Few RCTs address vascular dementia, and fewer still Lewy body dementia.
Some cognitive symptoms of dementia may be improved by acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine). Acetylcholinesterase inhibitors may improve cognitive function and global function scores compared with placebo at 12 to 26 weeks in people with Alzheimer's disease. However, they may be associated with an increase in adverse effects, particularly GI symptoms (anorexia, nausea, vomiting, or diarrhoea).
We don't know whether cognitive stimulation, music therapy, reminiscence therapy, omega 3 fish oil, statins, or NSAIDs are effective at improving cognitive outcomes in people with cognitive symptoms of dementia, as we found insufficient evidence.
In people with cognitive symptoms, memantine may modestly improve cognitive function and global function scores in people with Alzheimer's disease over 24 to 28 weeks, and may modestly improve activities of daily living scores in people with moderate to severe Alzheimer's disease. Although memantine is associated with a statistically significant increase in cognition scores in some population groups, the clinical importance of some of these results is unclear.
We found inconsistent evidence on the effects of ginkgo biloba on cognitive outcomes, which varied by the analysis performed. We found no evidence that ginkgo biloba improves activities of daily living outcomes, but the available evidence was weak.
Acetylcholinesterase inhibitors may marginally improve neuropsychiatric symptoms compared with placebo in people with behavioural and psychological symptoms of dementia, but they are also associated with adverse effects.
We don't know whether antidepressants (clomipramine, fluoxetine, imipramine, sertraline) improve depressive symptoms in people with Alzheimer's disease associated with depression. Many RCTs were small and short term, and adverse effects were sparsely reported.
Memantine may be associated with a small improvement in neuropsychiatric symptoms compared with placebo in people with behavioural and psychological symptoms of dementia, but it is also associated with adverse effects.
We don't know whether diazepam, lorazepam, aromatherapy, CBT, exercise, carbamazepine, or sodium valproate/valproic acid are effective at improving neuropsychiatric symptoms in people with behavioural and psychological symptoms of dementia, as we found insufficient evidence.
Some antipsychotics may improve neuropsychiatric symptoms or aggression in people with behavioural and psychological symptoms of dementia, but antipsychotics are also associated with an increased risk of severe adverse events such as stroke, TIA, or death.
CAUTION: Regulatory bodies have issued alerts that both conventional and atypical antipsychotics are associated with an increased risk of death in older people treated for dementia-related psychosis.
PMCID: PMC3437526  PMID: 23870856
16.  Clinical features and multidisciplinary approaches to dementia care 
Dementia is a clinical syndrome of widespread progressive deterioration of cognitive abilities and normal daily functioning. These cognitive and behavioral impairments pose considerable challenges to individuals with dementia, along with their family members and caregivers. Four primary dementia classifications have been defined according to clinical and research criteria: 1) Alzheimer’s disease; 2) vascular dementias; 3) frontotemporal dementias; and 4) dementia with Lewy bodies/Parkinson’s disease dementia. The cumulative efforts of multidisciplinary healthcare teams have advanced our understanding of dementia beyond basic descriptions, towards a more complete elucidation of risk factors, clinical symptoms, and neuropathological correlates. The characterization of disease subtypes has facilitated targeted management strategies, advanced treatments, and symptomatic care for individuals affected by dementia. This review briefly summarizes the current state of knowledge and directions of dementia research and clinical practice. We provide a description of the risk factors, clinical presentation, and differential diagnosis of dementia. A summary of multidisciplinary team approaches to dementia care is outlined, including management strategies for the treatment of cognitive impairments, functional deficits, and behavioral and psychological symptoms of dementia. The needs of individuals with dementia are extensive, often requiring care beyond traditional bounds of medical practice, including pharmacologic and non-pharmacologic management interventions. Finally, advanced research on the early prodromal phase of dementia is reviewed, with a focus on change-point models, trajectories of cognitive change, and threshold models of pathological burden. Future research goals are outlined, with a call to action for social policy initiatives that promote preventive lifestyle behaviors, and healthcare programs that will support the growing number of individuals affected by dementia.
doi:10.2147/JMDH.S17773
PMCID: PMC3104685  PMID: 21655340
dementia; Alzheimer’s disease; clinical features; multidisciplinary care; BPSD; prodromal dementia
17.  A clinico-epidemiological study of cognitive function status of community-dwelling elderly 
Indian Journal of Psychiatry  2014;56(4):365-370.
Background:
Cognitive decline and dementia are an important problem affecting quality-of-life in elderly and their caregivers. There is regional variation in prevalence of cognitive decline as well as risk factors from region to region.
Aim:
The aim was to determine the prevalence of dementia and cognitive decline and its various risk factors in the elderly population of more than 60 years in Eastern Uttar Pradesh (India).
Materials and Methods:
A camp-based study was conducted on rural population of Chiraigaon block of Varanasi district from February 2007 to May 2007. Block has 80 villages, of which 11 villages were randomly selected. Eleven camps were organized for elderly people in 11 randomly selected villages on predetermined dates. A total of 728 elderly persons of age >60 years were examined, interviewed and data thus collected was analyzed. Elderly who got Hindi-mini-mental state examination (HMSE) score developed by Ganguli based on the Indo-US Cross-National Dementia Epidemiology Study) score ≤23 were evaluated further and in those with confirmed cognitive and functional impairment, diagnosis of dementia was assigned according to Diagnostic and Statistical Manual for Mental Disorder fourth edition criteria after ruling out any psychiatric illness or delirium. Based on International Classification of Diseases-10 diagnostic criteria sub-categorization of dementia was done.
Results:
Mean, median and 10th percentile of HMSE of the study population were 23.4, 24 and 17, respectively. About 14.6% elderly had scored <17. 42.9% of rural elderly population had HMSE score <23, 70.6% <27 and 27.7% between 23 and 27. Literate people had statistically significant higher mean HMSE score (26.1 ± 3.9) than illiterate people (22.9 ± 4.9). Other risk factors were female gender, malnutrition, and obesity. Prevalence of dementia was 2.74%; in male 2.70% and in female 2.80%. Most common type of dementia was Alzheimer (male 1.5%, female 1.5%) followed by vascular (male 1.2%, female 0.6%) and others 0.6% (male 0%, female 0.6%).
Conclusions:
Study showed that a very high percentage of rural elderly attending health camps had poor cognitive function score; though the prevalence of dementia was relatively low. Alzheimer dementia was most common, followed by vascular dementia, which was predominant in males. Illiteracy, age, and under-nutrition were the most important risk factors for poor cognitive function. Our study suggest that cut-off of HMSE score should be 17 (10th percentile) for illiterate population.
doi:10.4103/0019-5545.146531
PMCID: PMC4279294  PMID: 25568477
Dementia; elderly; epidemiology
18.  The Appropriate Use of Neuroimaging in the Diagnostic Work-Up of Dementia 
Background
Diagnosis of dementia is challenging and requires both ruling out potentially treatable underlying causes and ruling in a diagnosis of dementia subtype to manage patients and suitably plan for the future.
Objectives
This analysis sought to determine the appropriate use of neuroimaging during the diagnostic work-up of dementia, including indications for neuroimaging and comparative accuracy of alternative technologies.
Data Sources
A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published between 2000 and 2013.
Review Methods
Data on diagnostic accuracy and impact on clinical decision making were abstracted from included studies. Quality of evidence was assessed using GRADE.
Results
The search yielded 5,374 citations and 15 studies were included. Approximately 10% of dementia cases are potentially treatable, though less than 1% reverse partially or fully. Neither prediction rules nor clinical indications reliably select the subset of patients who will likely benefit from neuroimaging. Clinical utility is highest in ambiguous cases or where dementia may be mixed, and lowest for clinically diagnosed Alzheimer disease or clinically excluded vascular dementia. There is a lack of evidence that MRI is superior to CT in detecting a vascular component to dementia. Accuracy of structural imaging is moderate to high for discriminating different types of dementia.
Limitations
There was significant heterogeneity in estimates of diagnostic accuracy, which often prohibited a statistical summary of findings. The quality of data reported by studies prohibited calculation of likelihood ratios in the present analysis. No studies from primary care were found; thus, generalizability beyond tertiary care settings may be limited.
Conclusions
A diagnosis of reversible dementia is rare. Imaging has the most clinical utility in cases where there is potentially mixed dementia or ambiguity as to the type of dementia despite prolonged follow-up (e.g., 2 years or more). Both CT and MRI are useful for detecting a vascular component of dementia.
Plain Language Summary
Dementia is a devastating condition of memory loss and behaviour change that affects many Canadians, especially older adults. Diagnosis is complex because symptoms can be caused by different brain diseases, such as Alzheimer disease, and in some cases by other causes such a tumour or cerebrovascular disease. Although dementia rarely improves much, an accurate diagnosis is important because it determines the treatment a patient should receive and helps patients and families understand what the future holds.
Brain imaging, using computed tomography (CT) or magnetic resonance imaging (MRI) scans, may help in the diagnosis by allowing doctors to see changes in brain structure or function that explain the dementia. Unfortunately, it is not well understood which patients will most likely benefit from a brain scan and which type of scan works best to diagnose dementia. This study reviewed the published evidence about these questions.
The study found that relying on specific symptoms to decide who should have a brain scan, rather than imaging all dementia patients, is unreliable and can miss some potentially treatable conditions. The study also found that scans have most value when doctors are uncertain as to the type of dementia despite monitoring the patient for a while (e.g., 2 years) or when the patient may have a combination of dementia types. Brain scans are often less helpful in the diagnosis of Alzheimer disease, and doctors can often use clinical assessment to rule out vascular dementia (another common type of dementia, related to cerebrovascular disease). The evidence also shows that MRI is not better than CT in detecting vascular dementia as a contributing cause. For Alzheimer disease, Creutzfeldt-Jakob disease, and clinically ambiguous dementias, both CT and MRI are highly accurate in correctly ruling out these diagnoses, but both types of scans have only low to moderate ability to correctly identify patients with any of these conditions. Importantly, the quality of the evidence available for this study was limited by considerable differences in research and analysis methods.
PMCID: PMC3937983  PMID: 24592296
19.  An epidemiological study of dementia under the aegis of mental health program, Maharashtra, Pune chapter 
Indian Journal of Psychiatry  2010;52(2):131-139.
Background:
There has been an exponential growth in the number of elderly population in India. This study aims to determine the prevalence of dementia in an urban center of Pune and to evaluate the corresponding socio-demographic correlates along with psychiatric morbidity in the study sample.
Materials and Methods:
The study population in Pune and Kirkee cantonments was selected based on 2001 census data. The number of people over 65 years numbered 6721 and 2145 of them were randomly selected for a door-to-door survey. They were initially administered household questionnaire and then subjected to a screening tool. Each participant underwent a brief mental state examination and data was collected on the basis of a structured proforma. Patients underwent a detailed cognitive profile using subtests from CSI-D (community screening instrument – dementia), which included a Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list, word fluency and delayed recall. Information pertaining to socio-demographic factors in participants and caregivers, caregiver-burden and behavioral and psychological symptoms in participants too were collected from the questionnaire. Radio imaging investigation was also carried out to quantify the deficit. Statistical Package for the Social Sciences (SPSS) software was used to compute the results.
Results:
Findings revealed that prevalence of dementia in the sample population of elderly aged above 65 years was 4.1%. Socio-demographic factors which conferred a statistically higher risk for dementia were identified to be older age, low socio-economic status, low level of education, presence of family history, whereas, marriage was found to be protective. Burden of care was associated with caring for elderly with dementia with increasing severity of dementia. Patients with dementia performed poorly on cognitive test battery. Social network had a protective effect in respect with severity of dementia. On magnetic resonance imaging (MRI) majority of cases of Alzheimer’s Dementia (AD) and Vascular Dementia (VaD) were noted to have both gray and white matter involvement.
Conclusion:
Poor awareness is a key public-health problem. Society plays an important role in the ageing process. The withdrawal of the elderly from the previous societal roles,reduction in all types of interactions i.e. shift of attention from outer world to the inner world, reduction in the power and prestige of the elderly enhance aging process. Aging in Indian culture though a disability is much stressful today in Indian culture as in others.
doi:10.4103/0019-5545.64588
PMCID: PMC2927882  PMID: 20838500
Alzheimer’s dementia; epidemiology of dementia; prevalence of dementia
20.  Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: The AIBL Active trial 
BMC Psychiatry  2012;12:167.
Background
Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging (MRI).
Methods/design
This single-blind randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). Participants must have SMC with or without MCI and at least one VRF. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography (PET) imaging comprise secondary measures.
Discussion
Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's disease pathologies.
Trial Registration
Australia New Zealand Clinical Trials Registry ACTRN12611000612910
doi:10.1186/1471-244X-12-167
PMCID: PMC3534144  PMID: 23050829
21.  Cognitive Decline and Dementia in the Oldest-Old 
The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer’s disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.
doi:10.5041/RMMJ.10092
PMCID: PMC3678827  PMID: 23908850
Dementia; epidemiology; neurobiology; oldest-old; risk factors
22.  A Population-based study of dementia in the oldest old: the Monzino 80-plus Study 
BMC Neurology  2011;11:54.
Background
Despite being the fastest growing and the most cognitively impaired age group, the oldest olds are under-represented in clinical research. The purpose of this study was to describe the design, methods, and baseline characteristics of the survey population and investigate possible differences in demographic, cognitive, functional, and behavioral characteristics between oldest old with and without any performance on cognitive tests and between oldest old alive and those deceased prior to the interview.
Methods
The Monzino 80-plus Study is a prospective door-to-door population-based survey among 80 years or older residents in the municipalities in the province of Varese, Italy. Dementia cases were identified with a one-phase design. Trained psychologists interviewed both the subject and a proxy informant. The interview included a comprehensive standardized questionnaire together with an array of rating scales and a multidomain cognitive battery to assess cognitive and functional ability, behavioral disturbances and mood.
Results
Information was available for 2,139 of the 2,428 registered individuals aged 80 years or older. Main baseline characteristics of the population are reported and discussed. In comparison with those living, elderly persons who had died before the first visit were older, had twice the rate of institutionalization, poorer cognitive performance and competence, and significantly greater instrumental and basic functional disability. The percentage of elderly persons, alive at baseline, without Mini-Mental State Examination rose rather evenly with age. Moreover, they had significantly worse cognitive competence and functional ability, and reported higher prevalences of depressive symptoms and problem behaviors than those with Mini-Mental State Examination.
Conclusions
Prospective investigation of a large population of oldest old can contribute significantly to understanding the relations between age, cognitive decline, and dementia occurrence. Use of informant-based instruments in surveys in the oldest old is crucial in assessing everyday functioning and changes, especially in participants with no cognitive test performance available. Failure to include information on deceased elderly would underestimate, increasingly with age, the prevalence of cognitive and functional disability in the elderly population.
doi:10.1186/1471-2377-11-54
PMCID: PMC3120664  PMID: 21612585
23.  Association of Lifetime Intellectual Enrichment with Cognitive Decline in the Older Population 
JAMA neurology  2014;71(8):1017-1024.
IMPORTANCE
Intellectual lifestyle enrichment throughout life is increasingly viewed as a protective strategy against commonly observed cognitive decline in the elderly.
OBJECTIVE
To investigate the association of lifetime intellectual enrichment with baseline cognitive performance and rate of cognitive decline in a non-demented elderly population and to estimate difference (in years) associated with lifetime intellectual enrichment to the onset of cognitive impairment.
DESIGN, SETTING, PARTICIPANTS
Prospective analysis of subjects enrolled in the Mayo Clinic Study of Aging (MCSA), a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We studied 1995 non-demented (1718 cognitively normal, 277 MCI) participants in MCSA who completed intellectual lifestyle measures at baseline and underwent at least one follow-up visit.
MAIN OUTCOMES AND MEASURES
We studied the effect of lifetime intellectual enrichment by separating the variables into two non-overlapping principal components: education/occupation-score and mid/late-life cognitive activity measure based on self-report questionnaires. A global cognitive Z-score served as our summary cognition measure. We used linear mixed-effects models to investigate the associations of demographic and intellectual enrichment measures with global cognitive Z-score trajectories.
RESULTS
Baseline cognitive performance was lower in older subjects and in those with lower education/occupation, lower mid/late-life cognitive activity, apolipoprotein E4 (APOE) genotype, and in men. The interaction between the two intellectual enrichment measures was significant such that the beneficial effect of mid/late-life cognitive activity on baseline cognitive performance was reduced with increasing education/occupation. Only baseline age, mid/late-life cognitive activity, and APOE4 genotype were significantly associated with longitudinal change in cognitive performance from baseline. For APOE4 carriers with high lifetime intellectual enrichment (75th percentile of both education/occupation and mid/late-life cognitive activity), the onset of cognitive impairment was about 8.7 years later compared with low lifetime intellectual enrichment (25th percentile of both education/occupation and mid/late-life cognitive activity) in an 80 year old subject.
CONCLUSIONS AND RELEVANCE
Higher levels of education/occupation were associated with higher levels of cognition. Higher levels of mid/late-life leisure activity were also associated with higher levels of cognition, but the slope of this relationship slightly increased over time. Lifetime intellectual enrichment might delay the onset of cognitive impairment and be used as a successful preventive intervention to reduce the impending dementia epidemic.
doi:10.1001/jamaneurol.2014.963
PMCID: PMC4266551  PMID: 25054282
24.  Can cognitive enhancers reduce the risk of falls in older people with Mild Cognitive Impairment? A protocol for a randomised controlled double blind trial 
BMC Neurology  2009;9:42.
Background
Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function.
Method/Design
Double blinded randomized controlled trial with 6 months follow-up in 140 older individuals with Mild Cognitive Impairment (MCI). Participants will be randomized to the intervention group, receiving donepezil, and to the control group, receiving placebo. A block randomization by four and stratification based on fall history will be performed. Primary outcomes are improvements in gait velocity and reduction in gait variability. Secondary outcomes are changes in the balance confidence, balance sway, attention, executive function, and number of falls.
Discussion
By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. This RCT study will provide, for the first time, information regarding the effect of a medication designed to augment cognitive functioning have on the risk of falls in older adults with Mild Cognitive Impairment. We expect a significant reduction in the risk of falls in this vulnerable population as a function of the reduced gait variability achieved by treatment with cognitive enhancers. This study may contribute to a new approach to prevent and treat fall risk in seniors in early stages of dementia.
Trial Registration
The protocol for this study is registered with the Clinical Trials Registry, identifier number: NCT00934531 http://www.clinicaltrials.gov
doi:10.1186/1471-2377-9-42
PMCID: PMC3224736  PMID: 19674471
25.  Cognitive Decline in Prodromal Alzheimer's Disease and Mild Cognitive Impairment 
Archives of neurology  2011;68(3):351-356.
Objective
To characterize the course of cognitive decline during the prodromal phase of Alzheimer's disease.
Design
Longitudinal cohort study with up to 16 years of observation.
Participants
Older persons from two projects underwent annual clinical evaluations that included cognitive function testing and clinical classification of mild cognitive impairment, dementia, and Alzheimer's disease. At baseline, there were 2,071 individuals without dementia and 1,511 without cognitive impairment.
Main Outcome Measures
Change in previously established composite measures of global cognition and specific cognitive domains assessed in mixed-effects models that allow rate of decline to shift at specific points.
Results
During follow-up, 462 persons developed Alzheimer's disease (20 with dementia solely due to another condition were excluded). Five to six years before the diagnosis, rate of global cognitive decline sharply accelerated by more than 15-fold. The acceleration in decline occurred slightly earlier for semantic memory (76 months before diagnosis) and working memory (75 months) than other cognitive functions. Mild cognitive impairment was also preceded by years of cognitive decline which began earlier (80 months before diagnosis) and proceeded more rapidly (annual loss of 0.102 unit) in the amnestic than nonamnestic (62 months, 0.072 unit) subtype.
Conclusion
Dementia due to Alzheimer's disease is preceded by about five to six years of accelerated decline in multiple cognitive functions. By contrast, little decline is evident in persons not developing Alzheimer's disease.
doi:10.1001/archneurol.2011.31
PMCID: PMC3100533  PMID: 21403020

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