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1.  Midlife overweight and obesity increase late-life dementia risk 
Neurology  2011;76(18):1568-1574.
Objective:
The relation of overweight to dementia is controversial. We aimed to examine the association of midlife overweight and obesity with dementia, Alzheimer disease (AD), and vascular dementia (VaD) in late life, and to verify the hypothesis that genetic and early-life environmental factors contribute to the observed association.
Methods:
From the Swedish Twin Registry, 8,534 twin individuals aged ≥65 (mean age 74.4) were assessed to detect dementia cases (DSM-IV criteria). Height and weight at midlife (mean age 43.4) were available in the Registry. Data were analyzed as follows: 1) unmatched case-control analysis for all twins using generalized estimating equation (GEE) models and 2) cotwin matched case-control approach for dementia-discordant twin pairs by conditional logistic regression taking into account lifespan vascular disorders and diabetes.
Results:
Among all participants, dementia was diagnosed in 350 subjects, and 114 persons had questionable dementia. Overweight (body mass index [BMI] >25–30) and obesity (BMI >30) at midlife were present in 2,541 (29.8%) individuals. In fully adjusted GEE models, compared with normal BMI (20–25), overweight and obesity at midlife were related to dementia with odds ratios (ORs) (95% CIs) of 1.71 (1.30–2.25) and 3.88 (2.12–7.11), respectively. Conditional logistic regression analysis in 137 dementia-discordant twin pairs led to an attenuated midlife BMI-dementia association. The difference in ORs from the GEE and the matched case-control analysis was statistically significant (p = 0.019).
Conclusions:
Both overweight and obesity at midlife independently increase the risk of dementia, AD, and VaD. Genetic and early-life environmental factors may contribute to the midlife high adiposity–dementia association.
doi:10.1212/WNL.0b013e3182190d09
PMCID: PMC3100125  PMID: 21536637
2.  Association between late-life body mass index and dementia 
Neurology  2009;72(20):1741-1746.
Objective:
To examine the association between body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) and risk of dementia and its subtypes in late life.
Methods:
Participants were members of the Kame Project, a population-based prospective cohort study of 1,836 Japanese Americans living in King County, WA, who had a mean age of 71.8 years and were dementia-free at baseline (1992–1994), and were followed for incident dementia through 2001. Cox proportional hazards models were used to estimate the risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD) controlling for demographic and lifestyle characteristics and vascular comorbidities as a function of baseline BMI, WC, and WHR and change in BMI over time.
Results:
Higher baseline BMI was significantly associated with a reduced risk of AD (hazard ratio [HR] = 0.56, 95% confidence interval [CI] = 0.33–0.97) in the fully adjusted model. Slower rate of decline in BMI was associated with a reduced risk of dementia (HR = 0.37, 95% CI = 0.14–0.98), with the association stronger for those who were overweight or obese (HR = 0.18, 95% CI = 0.05–0.58) compared to normal or underweight (HR = 1.00, 95% CI = 0.18–5.66) at baseline.
Conclusion:
Higher baseline body mass index (BMI) and slower declining BMI in late life are associated with a reduced risk of dementia, suggesting that low BMI or a faster decline in BMI in late life may be preclinical indicators of an underlying dementing illness, especially for those who were initially overweight or obese.
GLOSSARY
= Alzheimer disease;
= body mass index;
= confidence interval;
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= hazard ratio;
= vascular dementia;
= waist circumference;
= waist-to-hip ratio.
doi:10.1212/WNL.0b013e3181a60a58
PMCID: PMC2683740  PMID: 19451529
3.  Mid-life versus late-life depressive symptoms and risk of dementia: Differential effects for Alzheimer’s disease and vascular dementia 
Archives of general psychiatry  2012;69(5):493-498.
Context
Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia.
Objective, Design, Setting and Participants
To clarify the timing and etiology of the association, we examined depressive symptoms assessed in mid-life (1964–1973) and late-life (1994–2000) and the risks of dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) (2003–2009) in a retrospective cohort study of 13,535 long-term Kaiser Permanente members. Depressive symptoms were categorized as none, mid-life only, late-life only or both. Cox proportional hazards models (age as time-scale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD or VaD.
Main Outcome Measure
Any medical record diagnosis of dementia; Neurology clinic diagnosis of AD or VaD.
Results
Subjects had a mean (standard deviation) age of 81 (5) years in 2003; 58% were women and 25% were non-white. Depressive symptoms were present in 14.1% of subjects in mid-life only, 9.2% late-life only, and 4.2% both. Over 6 years, 23.1% were diagnosed with dementia (5.5% AD, 2.3% VaD). The adjusted hazard of dementia was increased by approximately 20% for mid-life depressive symptoms only (Hazard Ratio [95% confidence interval]: 1.19 [1.07, 1.32]), 70% for late-life symptoms only (1.72 [1.54, 1.92]), and 80% for both (1.77 [1.52, 2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a two-fold increase in AD risk (2.06 [1.67, 2.55]) whereas subjects with both mid-life and late-life symptoms had more than a three-fold increase in VaD risk (3.51 [2.44, 5.05]).
Conclusions
Depressive symptoms in mid-life or late-life are associated with an increased risk of developing dementia. Depression that begins in late-life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.
doi:10.1001/archgenpsychiatry.2011.1481
PMCID: PMC3704214  PMID: 22566581
4.  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
5.  Body mass index across midlife and cognitive change in late life 
Background
High midlife body mass index (BMI) has been linked to a greater risk of dementia in late life, but few have studied the effect of BMI across midlife on cognitive abilities and cognitive change in a dementia free sample.
Methods
We investigated the association between body mass index (BMI), measured twice across midlife (mean age 40 and 61 years, respectively), and cognitive change in four domains across two decades in the Swedish Adoption/Twin Study of Aging (SATSA).
Results
Latent growth curve models fitted to data from 657 non-demented participants showed that persons who were overweight/obese in early midlife had significantly lower cognitive performance across domains in late life and significantly steeper decline in perceptual speed, adjusting for cardio-metabolic factors. Both underweight and overweight/obesity in late midlife were associated with lower cognitive abilities in late life. However, the association between underweight and low cognitive abilities did not remain significant when weight decline between early and late midlife was controlled for.
Conclusions
There is a negative effect on cognitive abilities later in life related to being overweight/obese across midlife. Moreover, weight decline across midlife rather than low weight in late midlife per se was associated with low cognitive abilities. Weight patterns across midlife may be prodromal markers of late life cognitive health.
doi:10.1038/ijo.2012.37
PMCID: PMC3387354  PMID: 22450854
Aging; Body Mass Index; Cognition; Cognitive aging; Cognitive decline; Overweight; Obesity; Trajectories; Underweight; Weight changes
6.  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
7.  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
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.  Work-Related Stress May Increase the Risk of Vascular Dementia 
OBJECTIVES
We examined job control, job demands, social support at work, and job strain (ratio of demands to control) in relation to risk of any dementia, Alzheimer’s disease (AD), and vascular dementia (VaD).
DESIGN
A cohort study.
SETTING
The population-based Study of Dementia in Swedish Twins.
PARTICIPANTS
A total of 257 dementia cases (167 AD, 46 VaD) and 9,849 non-demented individuals.
MEASUREMENTS
Dementia diagnoses were based on telephone screening for cognitive impairment followed by in-person clinical work-up. An established job exposure matrix was matched to main occupation categories to measure work characteristics.
RESULTS
In generalized estimating equations (adjusted for the inclusion of complete twin pairs), lower job control was associated with greater risk of any dementia (odds ratio [OR]=1.17, 95% confidence interval [95%CI] 1.04-1.31) and VaD specifically (OR=1.39, 95% CI 1.07-1.81). Lower social support at work was associated with increased risk of dementia (OR=1.15, 95% CI 1.03-1.28), AD (OR=1.14, 95% CI 1.00-1.31), and VaD (OR=1.28, 95% CI=1.02-1.60). Greater job strain was associated with increased risk of VaD only (OR=1.28, 95% CI 1.02-1.60), especially in combination with low social support (OR=1.35, 95% CI 1.11-1.64). Age, gender, education, and cardiovascular disease were controlled. Results were not explained by work complexity or manual work. No differences in work-related stress scores were observed in the 54 twin pairs discordant for dementia, although only two pairs included a twin with VaD.
CONCLUSION
Work-related stress including low job control and low social support at work may increase the risk of dementia, particularly VaD. Modification to work environment that includes attention to social context and provision of meaningful roles for the workers may contribute to the efforts to promote cognitive health.
doi:10.1111/j.1532-5415.2011.03777.x
PMCID: PMC3258308  PMID: 22175444
Work-related stress; job strain; dementia; vascular dementia
10.  Lifestyle and the Risk of Dementia Among Japanese American Men 
Objectives
To determine whether adhering to a healthy lifestyle in midlife may reduce the risk of dementia.
Design
Case-control study nested in a prospective cohort.
Setting
The Honolulu-Asia Aging Study on Oahu, Hawaii.
Participants
3468 Japanese American men (mean age 52, 1965–1968) examined for dementia after 25 years.
Measurements
Men at low risk were defined as those with the following midlife characteristics: nonsmoking, body mass index <25.0 kg/m2, physically active, and having a healthy diet (based on alcohol, dairy, meat, fish, fruit, vegetables, cereals, and monounsaturated-to-saturated fat). Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for developing overall dementia, Alzheimer’s disease (AD), and vascular dementia (VaD), adjusting for potential confounders.
Results
Dementia was diagnosed in 6.4% of men (52.5% with AD, 35.0% with VaD). Examining the risk factors individually, BMI was most strongly associated with increased risk of overall dementia (OR, 1.87; 95% CI, 1.26–2.77; BMI >25.0 vs. <22.6 kg/m2). All of the individual risk factors except diet score were significantly associated with VaD, whereas none were significantly associated with AD alone. Men with all four low-risk characteristics (7.2% of cohort) had the lowest OR for overall dementia (OR, 0.36; 95% CI, 0.15–0.84), as compared to other men. There were no significant associations between the combined low-risk characteristics and the risk of AD alone.
Conclusion
Having a healthy lifestyle in midlife is associated with a lower risk of dementia in late life among Japanese American men.
doi:10.1111/j.1532-5415.2011.03768.x
PMCID: PMC3258374  PMID: 22211390
dementia; lifestyle; risk
11.  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
12.  Predicting risk of dementia in older adults 
Neurology  2009;73(3):173-179.
Objective:
To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years.
Methods:
Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients.
Results:
Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1–2 points), poor cognitive test performance (2–4 points), body mass index <18.5 (2 points), ≥1 apolipoprotein E ɛ4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79–0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores.
Conclusions:
The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.
GLOSSARY
= Modified Mini-Mental State Examination;
= Alzheimer disease;
= activities of daily living;
= body mass index;
= coronary artery bypass graft;
= Classification And Regression Tree;
= Center for Epidemiologic Studies–Depression Scale;
= congestive heart failure;
= Cardiovascular Health Study;
= confidence interval;
= Digit Symbol Substitution Test;
= instrumental activities of daily living;
= mild cognitive impairment;
= myocardial infarction;
= negative predictive value;
= peripheral artery disease;
= positive predictive value;
= receiver operating characteristic;
= upper extremity strength.
doi:10.1212/WNL.0b013e3181a81636
PMCID: PMC2715571  PMID: 19439724
13.  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
14.  Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis 
PLoS Medicine  2014;11(9):e1001713.
In this study, Proitsi and colleagues use a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset Alzheimer's Disease (LOAD) and find that genetic predisposition to increased plasma cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk.
Please see later in the article for the Editors' Summary
Background
Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD.
Methods and Findings
We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n = 10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10−8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10−8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR] = 1.005, 95% CI 0.82–1.24, p = 0.962 per 1 unit increase in HDL-c; OR = 0.901, 95% CI 0.65–1.25, p = 0.530 per 1 unit increase in LDL-c; OR = 1.104, 95% CI 0.89–1.37, p = 0.362 per 1 unit increase in triglycerides; and OR = 0.954, 95% CI 0.76–1.21, p = 0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance.
Conclusions
Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Currently, about 44 million people worldwide have dementia, a group of brain disorders characterized by an irreversible decline in memory, communication, and other “cognitive” functions. Dementia mainly affects older people and, because people are living longer, experts estimate that more than 135 million people will have dementia by 2050. The commonest form of dementia is Alzheimer disease. In this type of dementia, protein clumps called plaques and neurofibrillary tangles form in the brain and cause its degeneration. The earliest sign of Alzheimer disease is usually increasing forgetfulness. As the disease progresses, affected individuals gradually lose their ability to deal with normal daily activities such as dressing. They may become anxious or aggressive or begin to wander. They may also eventually lose control of their bladder and of other physical functions. At present, there is no cure for Alzheimer disease although some of its symptoms can be managed with drugs. Most people with the disease are initially cared for at home by relatives and other unpaid carers, but many patients end their days in a care home or specialist nursing home.
Why Was This Study Done?
Several lines of evidence suggest that lipid metabolism (how the body handles cholesterol and other fats) is altered in patients whose Alzheimer disease develops after the age of 60 years (late onset Alzheimer disease, LOAD). In particular, epidemiological studies (observational investigations that examine the patterns and causes of disease in populations) have found an association between high amounts of cholesterol in the blood in midlife and the risk of LOAD. However, observational studies cannot prove that abnormal lipid metabolism (dyslipidemia) causes LOAD. People with dyslipidemia may share other characteristics that cause both dyslipidemia and LOAD (confounding) or LOAD might actually cause dyslipidemia (reverse causation). Here, the researchers use “Mendelian randomization” to examine whether lifetime changes in lipid metabolism caused by genes have a causal impact on LOAD risk. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the effect of a modifiable risk factor and the outcome of interest. Because gene variants are inherited randomly, they are not prone to confounding and are free from reverse causation. So, if dyslipidemia causes LOAD, genetic variants that affect lipid metabolism should be associated with an altered risk of LOAD.
What Did the Researchers Do and Find?
The researchers investigated whether genetic predisposition to raised lipid levels increased the risk of LOAD in 10,578 participants (3,914 patients with LOAD, 1,675 elderly people without LOAD, and 4,989 population controls) using data collected in six genome wide studies looking for gene variants associated with Alzheimer disease. The researchers constructed a genotype risk score (GRS) for each participant using genetic risk markers for four types of blood lipids on the basis of the presence of single nucleotide polymorphisms (SNPs, a type of gene variant) in their DNA. When the researchers used statistical methods to investigate the association between the GRS and LOAD among all the study participants, they found no association between the GRS and LOAD.
What Do These Findings Mean?
These findings suggest that the genetic predisposition to raised blood levels of four types of lipid is not causally associated with LOAD risk. The accuracy of this finding may be affected by several limitations of this study, including the small proportion of lipid variance explained by the GRS and the validity of several assumptions that underlie all Mendelian randomization studies. Moreover, because all the participants in this study were white, these findings may not apply to people of other ethnic backgrounds. Given their findings, the researchers suggest that the observed epidemiological associations between abnormal lipid levels in the blood and variation in lipid levels for reasons other than genetics, or to LOAD risk could be secondary to variation in lipid levels for reasons other than genetics, or to LOAD, a possibility that can be investigated by studying blood lipid levels and other markers of lipid metabolism over time in large groups of patients with LOAD. Importantly, however, these findings provide new information about the role of lipids in LOAD development that may eventually lead to new therapeutic and public-health interventions for Alzheimer disease.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001713.
The UK National Health Service Choices website provides information (including personal stories) about Alzheimer's disease
The UK not-for-profit organization Alzheimer's Society provides information for patients and carers about dementia, including personal experiences of living with Alzheimer's disease
The US not-for-profit organization Alzheimer's Association also provides information for patients and carers about dementia and personal stories about dementia
Alzheimer's Disease International is the international federation of Alzheimer disease associations around the world; it provides links to individual associations, information about dementia, and links to World Alzheimer Reports
MedlinePlus provides links to additional resources about Alzheimer's disease (in English and Spanish)
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001713
PMCID: PMC4165594  PMID: 25226301
15.  Incidence of Dementia and Cognitive Impairment Not Dementia in the United States 
Annals of neurology  2011;70(3):418-426.
Objective
Estimates of incident dementia, and cognitive impairment, not dementia (CIND) (or the related mild cognitive impairment (MCI)) are important for public health and clinical care policy. In this paper, we report US national incidence rates for dementia and CIND.
Methods
Participants in the Aging, Demographic and Memory Study (ADAMS) were evaluated for cognitive impairment using a comprehensive in-home assessment. A total of 456 individuals age 72 and older, who were not demented at baseline were followed longitudinally from August 2001 to December 2009. An expert consensus panel assigned a diagnosis of normal cognition, CIND, or dementia and its subtypes. Using a population-weighted sample, we estimated the incidence of dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and CIND by age. We also estimated the incidence of progression from CIND to dementia.
Results
The incidence of dementia was 33.3 (s.e. = 4.2) per 1000 person-years and 22.9 (s.e. =2.9) per 1000 person-years for AD. The incidence of CIND was 60.4 (s.e.= 7.2) cases per 1000 person-years. An estimated 120.3 (s.e.=16.9) individuals per 1000 person-years progressed from CIND to dementia. Over a 5.9 year period, about 3.4 million individuals aged 72 and older in the US developed incident dementia; of which approximately 2.3 million developed AD and about 637,000 developed VaD. Over this same period, almost 4.8 million individuals developed incident CIND.
Interpretation
The incidence of CIND is greater than the incidence of dementia, and those with CIND are at high risk of progressing to dementia, making CIND a potentially valuable target for treatments aimed at slowing cognitive decline.
doi:10.1002/ana.22362
PMCID: PMC3139807  PMID: 21425187
16.  Mid- and Late-Life Diabetes in Relation to the Risk of Dementia 
Diabetes  2009;58(1):71-77.
OBJECTIVE—We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association.
RESEARCH DESIGN AND METHODS—This study included 13,693 twin individuals aged ≥65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression.
RESULTS—Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimer's disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51–2.38) for dementia, 1.69 (1.16–2.36) for Alzheimer's disease, and 2.17 (1.36–3.47) for vascular dementia. Compared with late-life diabetes (onset age ≥65 years), the risk effect of mid-life diabetes (onset age <65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05–5.51) and 0.68 (0.30–1.53) for dementia related to mid- and late-life diabetes, respectively.
CONCLUSIONS—Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes–dementia association but could not account for the mid-life diabetes–dementia association.
doi:10.2337/db08-0586
PMCID: PMC2606895  PMID: 18952836
17.  Cancer linked to Alzheimer disease but not vascular dementia 
Neurology  2010;74(2):106-112.
Objective:
To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD).
Methods:
Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study–Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer.
Results:
The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20–0.84) and pure AD (HR = 0.31, 95% CI = 0.12–0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52–0.997) and pure AD (HR = 0.57; 95% CI = 0.36–0.90) among white subjects after adjustment for demographics, number of APOE ε4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD.
Conclusions:
In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration.
GLOSSARY
= modified Mini-Mental State Examination;
= Alzheimer disease;
= Alzheimer Disease Diagnostic and Treatment Centers;
= coronary heart disease;
= Cardiovascular Health Study;
= confidence interval;
= hazard ratio;
= International Classification of Diseases–Ninth Revision;
= mild cognitive impairment;
= National Institute of Neurological and Communicative Diseases and Stroke–Alzheimer's Disease and Related Disorders Association;
= Parkinson disease;
= vascular dementia.
doi:10.1212/WNL.0b013e3181c91873
PMCID: PMC2809029  PMID: 20032288
18.  Body Adiposity in Later Life and the Incidence of Dementia: The Health in Men Study 
PLoS ONE  2011;6(3):e17902.
Objective
To determine if adiposity in later life increases dementia hazard.
Methods
Cohort study of 12,047 men aged 65–84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease.
Results
Compared with men with BMI<25, participants with BMI between 25–30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70–0.95). The HR of dementia for men with BMI≥30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67–1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR≥0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI = 0.69–0.98). We found a “J” shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR.
Conclusions
Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR≥0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9.
doi:10.1371/journal.pone.0017902
PMCID: PMC3064574  PMID: 21464984
19.  Body Adiposity in Late Life and Risk of Dementia or Cognitive Impairment in a Longitudinal Community-Based Study 
Background
The association between body adiposity at older ages and the development of cognitive impairment is unclear.
Methods
The association of body mass index (BMI) and waist circumference in late life with incidence of cognitive impairment was prospectively examined in a cohort study of 1,351 Latinos, aged 60–101 and residents of the Sacramento, CA, area at study baseline. The status of dementia and “cognitive impairment but not demented” (CIND) was determined at baseline and at each of five follow-up examinations by a multistage assessment protocol. Incident cases of dementia and CIND were combined (dementia/CIND) for more than 8 years of follow-up. BMI was categorized as less than 25.0, 25.0–29.9 (overweight), and 30 kg/m2 or greater (obese). Waist circumference was categorized into sex-specific tertiles.
Results
Dementia/CIND was diagnosed in 110 (8.2%) participants. Compared with the lowest BMI category, overweight participants had a 48% decreased rate of dementia/CIND (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.30–0.91) and obese participants had a 61% decreased rate of dementia/CIND (HR = 0.39, 95% CI: 0.20–0.78). Rates of dementia/CIND for the middle and high tertile of waist circumference, compared with the low tertile, were 80% and 90% higher, respectively (adjusted HR = 1.8, 95% CI: 1.1–3.1, and adjusted HR = 1.9, 95% CI: 0.91–3.8).
Conclusions
Abdominal fat in late life appears to confer an increased risk for dementia/CIND, whereas overall obesity appears to be protective. This may reflect age-related changes in body composition and the association of visceral fat with metabolic dysregulation.
doi:10.1093/gerona/gln006
PMCID: PMC2691186  PMID: 19168781
Adiposity; Dementia; Cognitive impairment; Body mass index; Waist circumference
20.  Change in the Body Mass Index Distribution for Women: Analysis of Surveys from 37 Low- and Middle-Income Countries 
PLoS Medicine  2013;10(1):e1001367.
Using cross-sectional surveys, Fahad Razak and colleagues investigate how the BMI (body mass index) distribution is changing for women in low- and middle-income countries.
Background
There are well-documented global increases in mean body mass index (BMI) and prevalence of overweight (BMI≥25.0 kg/m2) and obese (BMI≥30.0 kg/m2). Previous analyses, however, have failed to report whether this weight gain is shared equally across the population. We examined the change in BMI across all segments of the BMI distribution in a wide range of countries, and assessed whether the BMI distribution is changing between cross-sectional surveys conducted at different time points.
Methods and Findings
We used nationally representative surveys of women between 1991–2008, in 37 low- and middle-income countries from the Demographic Health Surveys ([DHS] n = 732,784). There were a total of 96 country-survey cycles, and the number of survey cycles per country varied between two (21/37) and five (1/37). Using multilevel regression models, between countries and within countries over survey cycles, the change in mean BMI was used to predict the standard deviation of BMI, the prevalence of underweight, overweight, and obese. Changes in median BMI were used to predict the 5th and 95th percentile of the BMI distribution. Quantile-quantile plots were used to examine the change in the BMI distribution between surveys conducted at different times within countries. At the population level, increasing mean BMI is related to increasing standard deviation of BMI, with the BMI at the 95th percentile rising at approximately 2.5 times the rate of the 5th percentile. Similarly, there is an approximately 60% excess increase in prevalence of overweight and 40% excess in obese, relative to the decline in prevalence of underweight. Quantile-quantile plots demonstrate a consistent pattern of unequal weight gain across percentiles of the BMI distribution as mean BMI increases, with increased weight gain at high percentiles of the BMI distribution and little change at low percentiles. Major limitations of these results are that repeated population surveys cannot examine weight gain within an individual over time, most of the countries only had data from two surveys and the study sample only contains women in low- and middle-income countries, potentially limiting generalizability of findings.
Conclusions
Mean changes in BMI, or in single parameters such as percent overweight, do not capture the divergence in the degree of weight gain occurring between BMI at low and high percentiles. Population weight gain is occurring disproportionately among groups with already high baseline BMI levels. Studies that characterize population change should examine patterns of change across the entire distribution and not just average trends or single parameters.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The number of obese people (individuals who have an excessive amount of body fat) is rapidly increasing in many countries. Globally, there were about 200 million obese adults in 1995; by 2010, 475 million adults were obese and another billion were classified as overweight. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30.0 kg/m2. Compared to people with a healthy weight (a BMI between 18.5 and 24.9 kg/m2), obese individuals and overweight individuals (who have a BMI between 25.0 and 29.9 kg/m2) have an increased risk of developing diabetes, heart disease and stroke, and tend to die younger. At the same time in many developing countries substantial numbers of people are underweight (BMI <18.5 kg/m2) or have chronic energy deficiency (BMI <16.0 kg/m2) and are at risk of increased risk of dying due to infectious disease or respiratory problems.
Why Was This Study Done?
The global obesity epidemic is usually described in terms of increases in the average BMI or in the prevalence of obesity (the proportion of the population whose BMI is above 30.0 kg/m2). Such descriptions assume that the BMIs of fat and thin people are increasing at the same rate and that the shape of the population's BMI distribution curve remains constant. However, as average BMI and the prevalence of obesity can increase it is unclear how the prevalence of underweight changes. This is potentially important for the health of the population because underweight individuals, like obese individuals, tend to die younger than healthy weight individuals, particularly in low-income countries. In this study, the researchers use repeated cross-sectional survey data collected from low- and middle-income countries in the Demographic and Health Surveys (DHS) to examine changes in BMI in women across the BMI distribution between 1991 and 2008. Repeated cross-sectional surveys collect data from a population at multiple time points from different individuals drawn from the same population, DHS are a data collection and surveillance project that help developing countries track health and population trends.
What Did the Researchers Do and Find?
The researchers used statistical models to analyze data from DHS surveys of more than 730,000 women living in 37 low- and middle-income countries (two to five surveys per country). Increasing average BMI was associated with an increase in the standard deviation of BMI (a measure of the dispersion of BMI in the population) both across and within countries over time. With increasing average BMI, the BMI at both the 5th and 95th percentile increased; 90% of the BMIs in a population lie between these percentiles so these BMI values indicate the spread of the BMI distribution. However, the BMI at the 95th percentile increased about 2.5 times faster than the BMI at the 5th percentile. Moreover, with increasing average BMI, the prevalence of overweight and obesity increased faster than the decline in the prevalence of underweight. Finally, quantile-quantile plots for each country (a graphical method that compares two distributions) revealed a consistent pattern of unequal weight gain across the BMI distribution as average BMI increased, with pronounced weight gains at the obese end of the distribution and little change at the underweight end.
What Do These Findings Mean?
These findings show that increases in average BMI are associated with an increased spread of BMI across and within populations. Consequently, changes in average BMI or single measurements such as the prevalence of overweight do not capture the divergence in the degree of weight gain occurring between that part of the population that has a low BMI and that part that has a high BMI. In other words, at least for the low- and middle-income countries included in this study, population weight gain is occurring disproportionately among groups with high baseline BMI levels. The researchers suggest, therefore, that the characterization of the BMI of populations over time should examine the patterns of change across the whole BMI distribution. Moreover, rather than a single broad population strategy for weight control, optimum health outcomes, they suggest, might be achieved by a strategy that includes targeted interventions to reduce weight in high BMI segments of the population and to increase weight in low BMI segments.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001367.
The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish)
The World Health Organization provides information on obesity (in several languages); Malri's story describes the health risks faced by an obese child
The UK National Health Service Choices website also provides detailed information about obesity and a link to a personal story about losing weight
The International Obesity Taskforce provides information about the global obesity epidemic
The US Department of Agriculture's ChooseMyPlate.gov website provides a personal healthy eating plan; the Weight-control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish)
MedlinePlus has links to further information about obesity (in English and Spanish)
doi:10.1371/journal.pmed.1001367
PMCID: PMC3545870  PMID: 23335861
21.  The Association Between Midlife Cardiorespiratory Fitness Levels and Later-Life Dementia 
Annals of internal medicine  2013;158(3):162-168.
Background
Primary prevention of Alzheimer disease and other types of dementia (all-cause dementia) is an important public health goal. Evidence to date is insufficient to recommend any lifestyle change to prevent or delay the onset of dementia.
Objective
To assess the association between objectively measured midlife cardiorespiratory fitness (“fitness”) levels and development of all-cause dementia in advanced age.
Design
Prospective, observational cohort study.
Setting
Preventive medicine clinic.
Patients
19 458 community-dwelling, nonelderly adults who had a baseline fitness examination.
Measurements
Fitness levels, assessed using the modified Balke treadmill protocol between 1971 and 2009, and incident all-cause dementia using Medicare Parts A and B claims data from 1999 to 2009.
Results
1659 cases of incident all-cause dementia occurred during 125 700 person-years of Medicare follow-up (median follow-up, 25 years [interquartile range, 19 to 30 years]). After multivariable adjustment, participants in the highest quintile of fitness level had lower hazard of all-cause dementia than those in the lowest quintile (hazard ratio, 0.64 [95% CI, 0.54 to 0.77]). Higher fitness levels were associated with lower hazard of all-cause dementia with previous stroke (hazard ratio, 0.74 [CI, 0.53 to 1.04]) or without previous stroke (hazard ratio, 0.74 [CI, 0.61 to 0.90]).
Limitations
Dementia diagnoses were based on Medicare claims, and participants generally were non-Hispanic white, healthy, and well-educated and had access to preventive health care. This study evaluated fitness levels, so a specific exercise prescription cannot be generated from results and the findings may not be causal.
Conclusion
Higher midlife fitness levels seem to be associated with lower hazards of developing all-cause dementia later in life. The magnitude and direction of the association were similar with or without previous stroke, suggesting that higher fitness levels earlier in life may lower risk for dementia later in life, independent of cerebrovascular disease.
doi:10.7326/0003-4819-158-3-201302050-00005
PMCID: PMC3926646  PMID: 23381040
22.  Midlife blood pressure, plasma β amyloid and the risk for Alzheimer’s disease: the Honolulu Asia Aging Study 
Hypertension  2012;59(4):780-786.
Beta-amyloid (Aβ), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer’s disease (AD) and possibly vascular dementia (VaD). We investigated the joint association of mid-life BP and Aβ peptide levels with the risk for late-life AD and VaD. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Program/Honolulu Asia Aging Study (1965 – 2000). Mid-life BP was measured starting in 1971 participants mean age 58 years, Aβ was measured in specimens collected1980/82, and assessment of dementia and autopsy collection started in 1991/93. The outcome measures were prevalent (present in 1991/3) and incident AD (n= 53, including 38 with no contributing cardiovascular disease), and VaD (n=24). Cerebral amyloid angiopathy (CAA), β-amyloid neuritic plaques, and neurofibrillary tangles were evaluated in post-mortem tissue. The risk for AD significantly increased with lower levels of plasma Aβ (Aβ1-40 hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.4 – 3.1; Aβ1-42 HR 1.6, 95% CI 1.1 – 2.3). Evidence of interaction between diastolic BP and plasma Aβ (1-40 pinteraction <0.05; 1-42 pinteraction <0.07) levels, indicated the Aβ-related risk for AD was higher when BP was higher. Low plasma Aβ was associated with the presence of CAA (ptrend<0.05), but not the other neuropathologies. Aβ plasma levels start decreasing at least 15 years before AD is diagnosed, and the association of Aβ to AD is modulated by mid-life diastolic BP. Elevated BP may compromise vascular integrity leading to CAA and impaired Aβ clearance from the brain.
doi:10.1161/HYPERTENSIONAHA.111.178962
PMCID: PMC3319436  PMID: 22392902
Amyloid; blood pressure; brain; aging; dementia
23.  Determinants of vascular dementia in the Cardiovascular Health Cognition Study 
Neurology  2005;64(9):1548-1552.
Objective
The authors evaluated 3,375 participants without dementia at the time of MRI in 1991 to 1994 over 5.7 years for incident dementia and type of dementia.
Methods
Incidence of and risk factors for vascular dementia (VaD) were measured using both pre-MRI and modified State of California Alzheimer’s Disease Diagnostic and Treatment Centers (ADDTC) post-MRI review and further classified Alzheimer disease (AD) by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDSADRDA) criteria.
Results
Approximately 44% (213) of 480 incident dementia cases were classified as possible or probable VaD by ADDTC. The incidence of VaD increased with age and was greater in blacks than whites. Risk factors for VaD included age, Modified Mini-Mental State Examination, high white matter grade, number of MRI infarcts, ventricular size, and history of stroke.
Conclusions
Vascular disease in the brain is prevalent among incident dementia cases. There is a substantial overlap between cases classified as Alzheimer disease by Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer’s Disease Diagnostic and Treatment Centers criteria. The substantial contribution of vascular disease would be missed without inclusion of MRI. Treatment of risk factors for VaD could have an important impact on incidence of dementia.
doi:10.1212/01.WNL.0000160115.55756.DE
PMCID: PMC3378359  PMID: 15883315
24.  Adiposity indicators and dementia over 32 years in Sweden 
Neurology  2009;73(19):1559-1566.
Background:
High midlife and late-life adiposity may increase risk for dementia. Late-life decrease in body mass index (BMI) or body weight within several years of a dementia diagnosis has also been reported. Differences in study designs and analyses may provide different pictures of this relationship.
Methods:
Thirty-two years of longitudinal body weight, BMI, waist circumference, and waist-to-hip ratio (WHR) data, from the Prospective Population Study of Women in Sweden, were related to dementia. A representative sample of 1,462 nondemented women was followed from 1968 at ages 38-60 years, and subsequently in 1974, 1980, 1992, and 2000, using neuropsychiatric, anthropometric, clinical, and other measurements. Cox proportional hazards regression models estimated incident dementia risk by baseline factors. Logistic regression models including measures at each examination were related to dementia among surviving participants 32 years later.
Results:
While Cox models showed no association between baseline anthropometric factors and dementia risk, logistic models showed that a midlife WHR greater than 0.80 increased risk for dementia approximately twofold (odds ratio 2.22, 95% confidence interval 1.00-4.94, p = 0.049) among surviving participants. Evidence for reverse causality was observed for body weight, BMI, and waist circumference in years preceding dementia diagnosis.
Conclusions:
Among survivors to age 70, high midlife waist-to-hip ratio may increase odds of dementia. Traditional Cox models do not evidence this relationship. Changing anthropometric parameters in years preceding dementia onset indicate the dynamic nature of this seemingly simple relationship. There are midlife and late-life implications for dementia prevention, and analytical considerations related to identifying risk factors for dementia.
GLOSSARY
= AD with cerebrovascular disease;
= body mass index;
= diastolic blood pressure; DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised;
= Honolulu Asia Aging Study;
= Prospective Population Study of Women;
= systolic blood pressure;
= socioeconomic status;
= vascular dementia;
= waist-to-hip ratio.
doi:10.1212/WNL.0b013e3181c0d4b6
PMCID: PMC2777073  PMID: 19901247
25.  Differences in Functional Impairment Across Subtypes of Dementia 
Background
Dementia is a cause of disability in later life. Despite the importance of functional status to the diagnosis of dementia, limited information exists on differences in functional limitations by dementia subtype. We conducted a cross-sectional analysis using the Aging, Demographics, and Memory Study (ADAMS) to determine the extent of functional impairment among older adults with dementia due to different etiologies.
Methods
The ADAMS sample consisted of 856 individuals aged 71 years and older originally surveyed as part of the Health and Retirement Study. Based on a comprehensive in-person cognitive evaluation, respondents were assigned to diagnostic categories of normal cognition, cognitive impairment not demented, and demented. Dementia subtypes were grouped into three categories: vascular dementia (VaD), Alzheimer’s dementia (AD), and dementia due to other etiologies. For 744 of the 856 respondents, a proxy informant completed a questionnaire asking whether the respondent had difficulty completing instrumental activities of daily living and activities of daily living (ADLs).
Results
Of 744 ADAMS participants, 263 had dementia: 199 (70.5%) with AD, 42 (16.9%) with VaD, and 22 (12.6%) were demented due to other etiologies. After adjustment for demographics, chronic illnesses, and dementia severity, participants with VaD (odds ratio [OR] 5.74; 95% confidence interval [CI] 2.60–12.69) and other etiologies of dementia (OR 21.23; 95% CI 7.25–62.16) were more likely to have greater than or equal to four ADL limitations compared with those with AD.
Conclusions
VaD is associated with significantly more ADL limitations than AD. These physical limitations should be considered when designing adult day care programs, which adequately accommodate the needs of non-AD patients.
doi:10.1093/gerona/glp197
PMCID: PMC2844058  PMID: 20018827
Activities of daily living; Instrumental activities of daily living; Disability; Dementia

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