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1.  Diagnosis and Staging of Mild Cognitive Impairment, using a modification of the Clinical Dementia Rating Scale: the mCDR 
To examine reliability and validity of the mCDR, a modified version of the Clinical Dementia Rating (CDR) scale.
The mCDR is an informant-based, technician-administered, structured interview with multiple choice responses, which does not include objective cognitive testing. Subjects (n=556) with no cognitive impairment (NCI), amnestic mild cognitive impairment (a-MCI), and Dementia were assessed with mCDR, CDR, and neuropsychological evaluation, while medial temporal atrophy (MTA) was measured on MRI scans. The mCDR and CDR were compared with respect to inter-rater reliability, validity, and ability to predict progression in cognitive diagnosis at 12 month follow-up.
The mCDR can be administered in less than a third of the time required to administer the CDR (30 minutes). Inter-rater reliability (Cohen's weighted Kappa) was 0.86 for the mCDR, and 0.56 for the CDR. Ability to distinguish between NCI, a-MCI, and Dementia subjects, and correlations to memory and non-memory measures were marginally better for the CDR, in comparison to the mCDR. Correlations of mCDR and CDR scores to MTA scores did not differ. Baseline mCDR scores predicted transition from NCI to aMCI, whereas baseline CDR scores predicted transition from aMCI to Dementia.
The mCDR, as compared to the CDR, is briefer, more reliable, and a valid measure of functional ability, among subjects with normal cognition, mild cognitive impairment, and mild dementia. The mCDR should be particularly useful as a reliable and economical instrument for assessing change in functional abilities, especially in multi-center clinical trials and population studies of MCI and mild dementia.
PMCID: PMC2822893  PMID: 19565573
Dementia; Clinical Rating Scale; Mild Cognitive Impairment; Visual Rating; MRI
2.  Symptoms of Early Dementia-11 Questionnaire (SED-11Q): A Brief Informant-Operated Screening for Dementia 
The aim of this study was to develop a brief informant-based questionnaire, namely the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), for the screening of early dementia. 459 elderly individuals participated, including 39 with mild cognitive impairment in the Clinical Dementia Rating scale (CDR) 0.5, 233 with mild dementia in CDR 1, 106 with moderate dementia in CDR 2, and 81 normal controls in CDR 0. Informants were required to fill out a 13-item questionnaire. Two items were excluded after analyzing sensitivities and specificities. The final version of the SED-11Q assesses memory, daily functioning, social communication, and personality changes. Receiver operator characteristic curves assessed the utility to discriminate between CDR 0 (no dementia) and CDR 1 (mild dementia). The statistically optimal cutoff value of 2/3, which indicated a sensitivity of 0.84 and a specificity of 0.90, can be applied in the clinical setting. In the community setting, a cutoff value of 3/4, which indicated a sensitivity of 0.76 and a specificity of 0.96, is recommended to avoid false positives. The SED-11Q reliably differentiated nondemented from demented individuals when completed by an informant, and thus is practical as a rapid screening tool in general practice, as well as in the community setting, to decide whether to seek further diagnostic confirmation.
PMCID: PMC3656692  PMID: 23687508
Dementia screening; Dementia; Alzheimer's disease; Activities of daily living; Cognitive deficits; Early detection; Mild cognitive impairment; Non-Alzheimer's disease

3.  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,, 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:
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
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.
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
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
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
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
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.
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
4.  Comparison of three instruments used in the assessment of dementia in Sri Lanka 
Indian Journal of Psychiatry  2005;47(2):109-112.
Dementia is poorly recognized even by physicians. This study compares three instruments used to assess dementia in a community setting in Sri Lanka.
Translated and culturally adapted versions of the Mini Mental State Examination (MMSE), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Clinical Dementia Rating (CDR) were administered to 363 individuals selected by stratified random sampling in a periurban community in Sri Lanka. The results on the three instruments were compared with the independent psychiatric evaluation done on a concentrated sample of 37 individuals from the study population.
Culturally adapted MMSE, IQCODE and CDR can be used to screen dementia in Sri Lanka. IQCODE is the best among the three instruments with a sensitivity of 71.4% and a specificity of 82.6% when 3.5 is the cut-off. In addition, IQCODE is culturally acceptable, easy to administer and can be used in those with a low level of literacy as well as in those with hearing or visual impairment.
IQCODE was found to be more effective and culturally acceptable as a screening tool for dementia in Sri Lanka, compared with MMSE and CDR.
PMCID: PMC2918294  PMID: 20711293
5.  The SIST-M: Development, reliability and cross-sectional validation of a brief structured Clinical Dementia Rating interview 
Archives of neurology  2011;68(3):343-350.
The Clinical Dementia Rating (CDR) and CDR-Sum-of-Boxes (CDR-SB) can be utilized to grade mild but clinically important cognitive symptoms. However, sensitive clinical interview formats are lengthy.
To develop a brief instrument for obtaining CDR scores, and to assess its reliability and cross-sectional validity.
Using legacy data from expanded interviews conducted among 347 community-dwelling, older adults in a longitudinal study, we identified 60 questions about cognitive functioning in daily life–out of a possible 131– using clinical judgment, inter-item correlations, and principal components analysis. Items were selected in one cohort (n=147), and a computer algorithm for generating CDR scores was developed in this same cohort and re-run in a replication cohort (n=200) to evaluate how well the 60 items retained information from the original 131. Then, short interviews based on the 60 items were administered to 50 consecutively-recruited elders, with no or mild cognitive symptoms, at an Alzheimer Disease Research Center. CDR scores based on short interviews were compared with those from independent long interviews.
In the replication cohort, agreement between short and long CDR interviews ranged from κ =0.65–0.79, with κ =0.76 for Memory; κ =0.77 for global CDR; ICC (intra-class correlation coefficient) for CDR-SB=0.89. In the cross-sectional validation, short interview scores were slightly lower than those from long interviews, but good agreement was observed: κ ≥ 0.70 for global CDR and Memory; ICC for CDR-SB=0.73.
The SIST-M is a brief, reliable and sensitive instrument for obtaining CDR scores in persons with symptoms along the spectrum of mild cognitive change.
PMCID: PMC3058542  PMID: 21403019
Alzheimer disease; mild cognitive impairment; Clinical Dementia Rating; instrument; questionnaire; clinical interview
6.  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.
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.
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
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
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)
PMCID: PMC3274506  PMID: 22346736
7.  Feasibility and Validity of Dementia Assessment by Trained Community Health Workers Based on Clinical Dementia Rating 
Ethnic minority elders, particularly recent Asian immigrants, have a heightened prevalence of dementia but lack timely diagnosis and treatment. This study was designed to determine the level of agreement between dementia rating by trained community health workers (CHWs) based on the Clinical Dementia Rating (CDR) and the gold standard, physician diagnosis.
Cross-sectional validation study.
Key community gathering places such as ethnic churches, senior centers, low-income elderly apartments, and ethnic groceries in the Baltimore-Washington metropolitan area.
Ninety community-dwelling Korean American elderly (aged 60 years or older).
The CDR is a standardized clinical dementia staging instrument to assess a patient’s cognitive and functional performance after a semi-structured interview protocol. A total of six CHWs who were trained and certified as CDR raters interviewed and rated study participants. A bilingual geriatric psychiatrist evaluated the participants independently for dementia status.
61.1% of the participants were rated as having either mild cognitive impairment (CDR=0.5) or dementia (CDR=1 or higher) by CHWs, as compared to 56.7% diagnosed by the clinician. A receiver operating characteristic (ROC) curve analysis demonstrated a good predictive capability for CDR rating by trained CHWs (ROC area under the curve=0.86 [95% confidence interval=0.78–0.93], with sensitivity=85.5% and specificity=88.6%) in detecting mild cognitive impairment and dementia.
The findings provide preliminary evidence that trained CHWs can effectively identify community-dwelling Korean elderly with mild cognitive impairment and dementia for early follow-up assessment and care in the resource scarce community.
PMCID: PMC3714359  PMID: 23730928
dementia; Clinical Dementia Rating; community health worker; Korean; elders
8.  Evaluation of Anosognosia in Alzheimer's Disease Using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q) 
The objective is to propose a brief method to evaluate anosognosia in Alzheimer's disease (AD) using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), a short informant-based screening questionnaire for identifying dementia.
The participants were 107 elderly individuals: 13 with a Clinical Dementia Rating (CDR) of 0.5, 73 with mild AD of CDR 1, and 21 with moderate AD of CDR 2. The patients and caregivers answered the SED-11Q independently, and the degree of discrepancy indicated the severity of anosognosia.
The scores were as follows: caregiver scores were 2.46 ± 1.85 (mean ± SD) in CDR 0.5, 6.36 ± 3.02 in CDR 1, and 9.00 ± 1.14 in CDR 2; patient scores were 2.00 ± 1.78, 2.55 ± 2.33, and 1.33 ± 2.46, respectively. Discrepancy was 0.46 ± 1.61, 3.81 ± 3.95, and 7.67 ± 2.87, respectively, and the caregiver assessments were significantly higher than the patient assessments in CDR 1 and CDR 2 (p < 0.001 in both groups). The SED-11Q for anosognosia was validated with the standardized Anosognosia Questionnaire for Dementia (AD-Q). The caregiver scores were moderately correlated with behavioral and psychological symptoms of dementia scores (r = 0.524), and the patient scores were moderately correlated with depression scores (r = 0.561).
The SED-11Q serves a dual purpose: caregiver assessment is useful for the screening of dementia, and any discrepancy between the patient and the caregiver assessment is considered as an indication of the severity of anosognosia; this can be informative for caregivers and essential for successful care.
PMCID: PMC3884202  PMID: 24403907
Anosognosia; Dementia; Alzheimer's disease; Behavioral and psychological symptoms of dementia; Metacognition; Caregiver burden; Dementia care; Mild cognitive impairment; Screening test

9.  A randomized controlled Alzheimer’s disease prevention trial’s evolution into an exposure trial: the PREADVISE trial 
To summarize the ongoing Prevention of Alzheimer’s Disease (AD) by Vitamin E and Selenium (PREADViSE) trial as a cooperative study to SELECT (a large prostate cancer prevention trial) and to present the blinded results of the first year as an exposure study.
PREADViSE was designed as a double blind randomized controlled trial (RCT).
SELECT terminated after 5.5 years of accrual and follow-up due to a futility analysis. Both trials then converted into an exposure study.
In the randomized component PREADViSE enrolled 7,547 men age 62 or older (60 if African American). Once the trial terminated 4,246 of these men volunteered for the exposure study. Demographics were similar for both groups with exposure volunteers having baseline mean age 67.3 ± 5.2 years, 15.3 ± 2.4 years of education, 9.8% African Americans, and 22% reporting a family history of dementia.
In the RCT men were randomly assigned to either daily doses of 400 IU of vitamin E or placebo and/or 200 μg of selenium or placebo using a 2×2 factorial structure.
In the RCT, participants completed the brief Memory Impairment Screen (MIS) and if they failed, underwent a longer screening (based on an expanded Consortium to Establish a Registry in AD [CERAD] battery). CERAD failure resulted in visits to their clinician for medical examination with records of these examinations forwarded to the PREADViSE center for further review. In the exposure study, men are contacted by telephone and complete the MIS-T screen. If they fail the MIS-T a Modified Telephone Interview of Cognitive Status (TICS-M) exam is given. A failed TICS-M exam also leads to a visit to their clinician for an in depth examination and forwarding of records for a centralized consensus diagnosis by expert clinicians. A subgroup of the men who pass the MIS-T also take the TICS-M exam for validation purposes.
While this ancillary trail was open to all 427 SELECT clinical sites, only 34% chose to participate in PREADViSE. Continual staff turnover at the sites presented challenges when training persons unfamiliar with cognitive testing procedures to conduct the memory screens. In the RCT few participants (1.6%) failed the MIS screen and among those who passed this screen a significant practice effect was encountered.
In the exposure study 3,581 men were reached by phone in year 1, 15.7% could not be reached after 5 calls, and of those contacted 6.0% refused the screen even after consenting to the procedures at their clinical site. Most notable is that the failure rate for the MIS-T increased fourfold to 7.2%. Of the 257 men who took the TICS-M, 84% failed and were asked to contact their physicians for a more detailed memory assessment and approximately half of these had some form of dementia or cognitive impairment. Several of these dementia cases are not AD.
Partnering with SELECT led to an AD prevention trial conducted at a very reasonable cost by taking advantage of the experience and efficient clinical trial management found in a cancer cooperative group (SWOG). Once unblinded, the RCT and exposure study data have the potential to yield new information on long term exposure to antioxidant supplements under controlled conditions.
PMCID: PMC3636980  PMID: 23299383
Alzheimer’s disease; prevention; telephone screening; cognitive assessments; case ascertainment
10.  An epidemiological study of dementia under the aegis of mental health program, Maharashtra, Pune chapter 
Indian Journal of Psychiatry  2010;52(2):131-139.
There has been an exponential growth in the number of elderly population in India. This study aims to determine the prevalence of dementia in an urban center of Pune and to evaluate the corresponding socio-demographic correlates along with psychiatric morbidity in the study sample.
Materials and Methods:
The study population in Pune and Kirkee cantonments was selected based on 2001 census data. The number of people over 65 years numbered 6721 and 2145 of them were randomly selected for a door-to-door survey. They were initially administered household questionnaire and then subjected to a screening tool. Each participant underwent a brief mental state examination and data was collected on the basis of a structured proforma. Patients underwent a detailed cognitive profile using subtests from CSI-D (community screening instrument – dementia), which included a Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list, word fluency and delayed recall. Information pertaining to socio-demographic factors in participants and caregivers, caregiver-burden and behavioral and psychological symptoms in participants too were collected from the questionnaire. Radio imaging investigation was also carried out to quantify the deficit. Statistical Package for the Social Sciences (SPSS) software was used to compute the results.
Findings revealed that prevalence of dementia in the sample population of elderly aged above 65 years was 4.1%. Socio-demographic factors which conferred a statistically higher risk for dementia were identified to be older age, low socio-economic status, low level of education, presence of family history, whereas, marriage was found to be protective. Burden of care was associated with caring for elderly with dementia with increasing severity of dementia. Patients with dementia performed poorly on cognitive test battery. Social network had a protective effect in respect with severity of dementia. On magnetic resonance imaging (MRI) majority of cases of Alzheimer’s Dementia (AD) and Vascular Dementia (VaD) were noted to have both gray and white matter involvement.
Poor awareness is a key public-health problem. Society plays an important role in the ageing process. The withdrawal of the elderly from the previous societal roles,reduction in all types of interactions i.e. shift of attention from outer world to the inner world, reduction in the power and prestige of the elderly enhance aging process. Aging in Indian culture though a disability is much stressful today in Indian culture as in others.
PMCID: PMC2927882  PMID: 20838500
Alzheimer’s dementia; epidemiology of dementia; prevalence of dementia
11.  Social Isolation in Community-Dwelling Seniors 
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,, 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)
Objective of the Evidence-Based Analysis
The objective was to systematically review interventions aimed at preventing or reducing social isolation and loneliness in community-dwelling seniors, that is, persons ≥ 65 years of age who are not living in long-term care institutions. The analyses focused on the following questions:
Are interventions to reduce social isolation and/or loneliness effective?
Do these interventions improve health, well-being, and/or quality of life?
Do these interventions impact on independent community living by delaying or preventing functional decline or disability?
Do the interventions impact on health care utilization, such as physician visits, emergency visits, hospitalization, or admission to long-term care?
Background: Target Population and Condition
Social and family relationships are a core element of quality of life for seniors, and these relationships have been ranked second, next to health, as the most important area of life. Several related concepts—reduced social contact, being alone, isolation, and feelings of loneliness—have all been associated with a reduced quality of life in older people. Social isolation and loneliness have also been associated with a number of negative outcomes such as poor health, maladaptive behaviour, and depressed mood. Higher levels of loneliness have also been associated with increased likelihood of institutionalization.
Note: It is recognized that the terms “senior” and “elderly” carry a range of meanings for different audiences; this report generally uses the former, but the terms are treated here as essentially interchangeable.
Methods of the Evidence-Based Analysis
The scientific evidence base was evaluated through a systematic literature review. The literature searches were conducted with several computerized bibliographic databases for literature published between January 1980 and February 2008. The search was restricted to English-language reports on human studies and excluded letters, comments and editorials, and case reports. Journal articles eligible for inclusion in the review included those that reported on single, focused interventions directed towards or evaluating social isolation or loneliness; included, in whole or in part, community-dwelling seniors (≥ 65 years); included some quantitative outcome measure on social isolation or loneliness; and included a comparative group. Assessments of current practices were obtained through consultations with various individuals and agencies including the Ontario Community Care Access Centres and the Ontario Assistive Devices Program. An Ontario-based budget impact was also assessed for the identified effective interventions for social isolation.
A systematic review of the published literature focusing on interventions for social isolation and loneliness in community-dwelling seniors identified 11 quantitative studies. The studies involved European or American populations with diverse recruitment strategies, intervention objectives, and limited follow-up, with cohorts from 10 to 15 years ago involving mainly elderly women less than 75 years of age. The studies involved 2 classes of interventions: in-person group support activities and technology-assisted interventions. These were delivered to diverse targeted groups of seniors such as those with mental distress, physically inactive seniors, low-income groups, and informal caregivers. The interventions were primarily focused on behaviour-based change. Modifying factors (client attitude or preference) and process issues (targeting methods of at-risk subjects, delivery methods, and settings) influenced intervention participation and outcomes.
Both classes of interventions were found to reduce social isolation and loneliness in seniors. Social support groups were found to effectively decrease social isolation for seniors on wait lists for senior apartments and those living in senior citizen apartments. Community-based exercise programs featuring health and wellness for physically inactive community-dwelling seniors also effectively reduced loneliness. Rehabilitation for mild/moderate hearing loss was effective in improving communication disabilities and reducing loneliness in seniors. Interventions evaluated for informal caregivers of seniors with dementia, however, had limited effectiveness for social isolation or loneliness.
Research into interventions for social isolation in seniors has not been broadly based, relative to the diverse personal, social, health, economic, and environmentally interrelated factors potentially affecting isolation. Although rehabilitation for hearing-related disability was evaluated, the systematic review did not locate research on interventions for other common causes of aging-related disability and loneliness, such as vision loss or mobility declines. Despite recent technological advances in e-health or telehealth, controlled studies evaluating technology-assisted interventions for social isolation have examined only basic technologies such as phone- or computer-mediated support groups.
Although effective interventions were identified for social isolation and loneliness in community-dwelling seniors, they were directed at specifically targeted groups and involved only a few of the many potential causes of social isolation. Little research has been directed at identifying effective interventions that influence the social isolation and other burdens imposed upon caregivers, in spite of the key role that caregivers assume in caring for seniors. The evidence on technology-assisted interventions and their effects on the social health and well-being of seniors and their caregivers is limited, but increasing demand for home health care and the need for efficiencies warrant further exploration. Interventions for social isolation in community-dwelling seniors need to be researched more broadly in order to develop effective, appropriate, and comprehensive strategies for at-risk populations.
PMCID: PMC3377559  PMID: 23074510
12.  A novel approach to assessing memory at the population level: Vulnerability to semantic interference 
There is increasing interest in identifying novel cognitive paradigms to help detect preclinical dementia. Promising results have been found in clinical settings using the Semantic Interference Test (SIT), a modification of an existing episodic memory test (Fuld Object Memory Evaluation) that exploits vulnerability to semantic interference in Alzheimer’s disease. It is not yet known how broadly this work will generalize to the community at large.
Participants aged ≥65 years from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) were administered the SIT at study entry. Independent of neuropsychological assessment, participants were rated on the Clinical Dementia Rating (CDR) scale, based on reported loss of cognitively-driven everyday functioning. In individuals free of dementia (CDR <1), the concurrent validity of the SIT was assessed by determining its association with CDR using multiple logistic regression models, with CDR 0 (no dementia) vs. 0.5 (possible dementia) as the outcome and the SIT test variables as predictors.
Poorer performance on all SIT variables but one was associated with higher CDR reflecting possible dementia (Odds Ratios 2.24 to 4.79). Younger age and female gender also conferred a performance advantage. Years of education and reading ability (a proxy for quality of education) evidenced a very weak association with SIT performance.
The SIT shows promise as a valid, novel measure to identify early preclinical dementia in a community setting. It has potential utility for assessment of persons who may be illiterate or of low education. Finally, we provide normative SIT data stratified by age which may be utilized by clinicians or researchers in future investigations.
PMCID: PMC2891858  PMID: 20105350
neuropsychological tests; norms; cognitive aging; Semantic Interference Test; Alzheimer’s disease
13.  Caregiver coping strategies predict cognitive and functional decline in dementia: The Cache County Dementia Progression Study 
Few longitudinal studies have studied the influence of the care environment on the clinical progression of dementia. We examined whether caregiver coping strategies predict dementia progression in a population-based sample.
Longitudinal, prospective cohort study
Cache County (Utah) Population
226 persons with dementia, and their caregivers, assessed semi-annually for up to 6 years.
Ways of Coping Checklist-Revised, Mini-Mental State Exam (MMSE), Clinical Dementia Rating (CDR).
Mean (SD) age of dementia onset was 82.11 (5.84) and mean caregiver age was 67.41 (13.95). Mean (SD) follow-up was 1.65 (1.63) years from baseline. In univariate linear mixed effects models, increasing use of problem-focused and counting blessings by caregivers was associated with slower patient worsening on the MMSE. Problem-focused coping, seeking social support, and wishful thinking were associated with slower CDR-SB worsening. Considering covariates, increasing use of problem-focused coping was associated with 0.70 points per year less worsening on the MMSE and 0.55 point per year less worsening on the CDR-sb. Compared to no use, “regular” use of this strategy was associated with a 2-point per year slower worsening on the MMSE and 1.65-point per year slower worsening on the CDR-sb.
Caregiver coping strategies are associated with slower dementia progression. Developing interventions that target these strategies may benefit dementia patients.
PMCID: PMC3502653  PMID: 23290203
dementia; Alzheimer’s disease; caregiver coping; stress coping; problem focused coping; dementia caregiving; dementia progression; cognitive decline; functional decline
14.  Reliability and Validity of the Clinical Dementia Rating for Community-Living Elderly Subjects without an Informant 
The Clinical Dementia Rating (CDR) scale is widely used to assess cognitive impairment in Alzheimer's disease. It requires collateral information from a reliable informant who is not available in many instances. We adapted the original CDR scale for use with elderly subjects without an informant (CDR-NI) and evaluated its reliability and validity for assessing mild cognitive impairment (MCI) and dementia among community-dwelling elderly subjects.
At two consecutive visits 1 week apart, nurses trained in CDR assessment interviewed, observed and rated cognitive and functional performance according to a protocol in 90 elderly subjects with suboptimal cognitive performance [Mini-Mental State Examination (MMSE) <26 and/or Montreal Cognitive Assessment (MOCA) <26] and without informants according to a protocol. CDR domains and global scores were assigned after the second visit based upon corroborative information from the subjects' responses to questions, role-play, and observed performance in specifically assigned tasks at home and within the community.
The CDR-NI scores (0, 0.5, 1) showed good internal consistency (Crohnbach's α 0.83-0.84), inter-rater reliability (κ 0.77-1.00 for six domains and 0.95 for global rating) and test-retest reliability (κ 0.75-1.00 for six domains and 0.80 for global rating), good agreement (κ 0.79) with the clinical assessment status of MCI (n = 37) and dementia (n = 4) and significant differences in the mean scores for MMSE, MOCA and Instrumental Activities of Daily Living (ANOVA global p < 0.001).
Owing to the protocol of the interviews, assessments and structured observations gathered during the two visits, CDR-NI provides valid and reliable assessment of MCI and dementia in community-living elderly subjects without an informant.
PMCID: PMC3843919  PMID: 24348502
Mild cognitive impairment; Clinical Dementia Rating; Alzheimer's disease; 
Community-living elderly subjects; Mini-Mental State Examination; Neuropsychological tests

15.  Outcomes of mild cognitive impairment depend on definition: a population study 
Archives of neurology  2011;68(6):761-767.
To determine the one-year outcomes of individuals classified as having mild cognitive impairment (MCI) by different definitions at the population level.
Inception cohort, one-year followup. Participants classified as MCI using the following definitions operationalized for this study: Amnestic MCI by Mayo criteria, Expanded MCI by International Working Group criteria, Clinical Dementia Rating (CDR)=0.5, and a purely cognitive classification into Amnestic and Non-amnestic MCI.
General community.
Stratified random population-based sample of 1982 individuals aged 65+ years.
Main Outcome Measures
For each MCI definition, three outcomes: worsening ( progression to dementia (CDR≥1) or severe cognitive impairment); improvement (reversion to CDR=0 or normal cognition); and stability (unchanged CDR or cognitive status).
Regardless of MCI definition, over one year, a small proportion progressed to CDR ≥ 1 (range 0–3%) or severe cognitive impairment (0–20%) at rates higher than their cognitively normal peers. Somewhat larger proportions improved or reverted to normal (6–53%). The majority remained stable (29–88%). Where definitions focused on memory impairment, and on multiple cognitive domains, higher proportions progressed and lower proportions reverted on CDR.
MCI as ascertained by several operational definitions is a heterogeneous entity at the population level but progresses to dementia at rates higher than in normal elderly. Proportions progressing to dementia are lower, and proportions reverting to normal are higher, than in clinical populations. Memory impairments and impairments in multiple domains lead to greater progression and lesser improvement. Research criteria may benefit from validation at the community level before incorporation into clinical practice.
PMCID: PMC3135309  PMID: 21670400
aging; community; population; epidemiology; MCI; dementia
16.  The SIST-M: Predictive validity of a brief structured Clinical Dementia Rating interview 
We previously established reliability and cross-sectional validity of the SIST-M (Structured Interview and Scoring Tool–Massachusetts Alzheimer's Disease Research Center), a shortened version of an instrument shown to predict progression to Alzheimer disease (AD), even among persons with very mild cognitive impairment (vMCI).
To test predictive validity of the SIST-M.
Participants were 342 community-dwelling, non-demented older adults in a longitudinal study. Baseline Clinical Dementia Rating (CDR) ratings were determined by either: 1) clinician interviews or 2) a previously developed computer algorithm based on 60 questions (of a possible 131) extracted from clinician interviews. We developed age+gender+education-adjusted Cox proportional hazards models using CDR-sum-of-boxes (CDR-SB) as the predictor, where CDR-SB was determined by either clinician interview or algorithm; models were run for the full sample (n=342) and among those jointly classified as vMCI using clinician- and algorithm-based CDR ratings (n=156). We directly compared predictive accuracy using time-dependent Receiver Operating Characteristic (ROC) curves.
AD hazard ratios (HRs) were similar for clinician-based and algorithm-based CDR-SB: for a 1-point increment in CDR-SB, respective HRs (95% CI)=3.1 (2.5,3.9) and 2.8 (2.2,3.5); among those with vMCI, respective HRs (95% CI) were 2.2 (1.6,3.2) and 2.1 (1.5,3.0). Similarly high predictive accuracy was achieved: the concordance probability (weighted average of the area-under-the-ROC curves) over follow-up was 0.78 vs. 0.76 using clinician-based vs. algorithm-based CDR-SB.
CDR scores based on items from this shortened interview had high predictive ability for AD – comparable to that using a lengthy clinical interview.
PMCID: PMC3257375  PMID: 21986342
Alzheimer disease; mild cognitive impairment; dementia; CDR; instrument; questionnaire; validity; prediction; psychometric
17.  Progression of Alzheimer disease as measured by Clinical Dementia Rating sum of boxes scores 
This study examined rates of dementia progression as ascertained by the Clinical Dementia Rating sum of boxes (CDR-SB) for symptomatic Alzheimer disease (sAD) and assessed participant characteristics as predictors of CDR-SB progression.
Participants (n = 792) were enrolled in longitudinal studies at an Alzheimer’s Disease Research Center, received a diagnosis of sAD with a global CDR of 0.5 (n = 466) or 1 (n = 326), and had at least one follow-up assessment. Progression in CDR-SB over time as a function of baseline global CDR was examined.
A longitudinal increase (p<.0001) in CDR-SB was observed. The annual rate of change in CDR-SB scores was 1.43 (SE=.05) in the CDR 0.5 sample and 1.91 (SE=.07) in the CDR 1 sample. For participants followed from the beginning of the CDR stage, time to progression to a higher global CDR was longer for individuals who were CDR 0.5 (3.75 years; 95% CI 3.18-4.33) than those who were CDR 1 at baseline (2.98 years; 95%CI 2.75-3.22). In the total CDR 0.5 sample, the significant predictors of progression to the next global CDR stage (p<.01) were age at first sAD diagnosis and apolipoprotein E4 genotype.
The study findings are relevant to sAD clinical trial design and accurate, reliable ascertainment of the effect of disease-modifying treatments.
PMCID: PMC3660405  PMID: 22858530
Alzheimer disease; assessment of dementia; Clinical Dementia Rating; Clinical Dementia Rating sum of boxes; cohort studies
18.  A brief clinical tool to assess physical function: The mini physical performance test 
The aim was to develop a brief physical performance assessment tool that can be reliably used to detect physical impairment in older adults with and without mild dementia. Scores on the 9-item physical performance test (PPT) from non-demented participants were used to develop and validate the 4-item mini-PPT. The validated mini-PPT was then used to predict total PPT score and functional physical status in participants with mild dementia. Receiver Operating Curve (ROC) analyses were used to generate a cut off score that classifies participants as functional vs. not functional. The setting was in the Alzheimer’s Disease Research Center (Washington University). A total of 1,199 participants met inclusion criteria: 574 non demented participants, 436 with very mild dementia, measured by the clinical dementia rating (CDR) = 0.5 and 189 with mild dementia (CDR = 1). The mean age of the sample was 76.4 years, mean educational attainment was 14 years, 58% were women, and 11% were African American. A 4-item scale, the mini-PPT, was developed (based on the results of multiple regression analyses and clinical meaningfulness) that highly correlated with total PPT score (r = 0.917, p < 0.0001) in the non-demented sample The correlation of the mini-PPT with total PPT was 0.90 among those with very mild, and 0.91 among those with mild dementia. Using the ROCs, a cut off score of 12 correctly classified at least 85% of non demented and demented persons. The 4-item mini-PPT is highly correlated with the 9-item PPT in non demented and mildly demented persons. This brief tool may be useful in detecting early physical impairment in the clinical setting.
PMCID: PMC2787987  PMID: 19282039
physical performance; assessment of physical performance; Alzheimer’s disease; dementia
To compare rates of Mild Cognitive Impairment (MCI) and rates of progression to dementia, using different MCI diagnostic systems
MCI was investigated at baseline in 3063 community-dwelling non-demented elderly in the Ginkgo Evaluation of Memory (GEM) study who were evaluated every six months to identify presence of dementia. Overall MCI frequency was determined using (1) Clinical Dementia Rating (CDR) score of 0.5 and (2) neuropsychological (NP) criteria, defined by impairment on standard cognitive tests.
40.2% of participants met CDR MCI criteria and 28.2% met NP MCI criteria (amnestic-MCI=16.6%). 15.7% were classified as MCI by both criteria and 47.4% as Normal by both. Discordant diagnoses were observed in 24.5% who met NP Normal/CDR MCI; and 12.4% who met NP MCI/CDR Normal. Factors associated with CDR MCI among NP Normal included, lower education, lower NP scores, more IADL impairment, greater symptoms of depression and subjective health problems. Individuals meeting NP MCI/CDR normal were significantly more likely to develop dementia over the median follow up of 6.1 years than those meeting NP Normal/CDR MCI.
Different criteria produce different MCI rates and different conversion rates to dementia. Although a higher percentage of MCI was identified by CDR than NP, a higher percentage of NP MCI progressed to dementia. These findings suggest that the CDR is sensitive to subtle changes in cognition not identified by NP algorithm but is also sensitive to demographic and clinical factors probably leading to a greater number of false positives. These results suggest that identifying all individuals with CDR scores of 0.5 as Alzheimer's disease is not advisable.
PMCID: PMC2698042  PMID: 19279031
Clinical Dementia Rating Scale; Neuropsychological tests
20.  Stability of the Clinical Dementia Rating: 1979–2007 
Archives of neurology  2009;66(6):773-777.
Diagnostic drift characterizes change in diagnosis and diagnostic classification over time. The Clinical Dementia Rating (CDR) is used commonly in dementia diagnosis and staging of dementia severity. Whether increasing efforts to diagnose dementia at earlier symptomatic stages has led to diagnostic drift in the CDR is unknown.
To examine dementia severity as determined by the CDR over time.
Secondary analysis of data from longitudinal studies of aging and dementia.
An Alzheimer’s Disease Research Center (ADRC), where a variety of clinicians contributed CDR ratings over the course of the study.
Adults aged 63 to 83 years with no (CDR 0), very mild (CDR 0.5) or mild (CDR 1) dementia enrolled in the ADRC at any time from August 1979 to May 2007.
Main Outcome Measures
Within each CDR group changes in scores on standardized psychometric tests with time were examined using multiple linear regression analyses. These tests included the Mini Mental State Examination, Short Blessed Test, Wechsler Memory Scale Logical Memory IA-Immediate, Blessed Dementia Scale, and a psychometric composite score.
A total of 1768 participants met inclusion criteria. Over time, participants were older, more educated, more likely to be minorities, and less likely to be male. Statistically significant change in psychometric test performance over time occurred only within the CDR 1 group for Logical Memory and the psychometric composite, but the degree of change was minimal.
Despite changes in participant characteristics, the CDR demonstrates general stability for assessment of dementia over almost three decades.
PMCID: PMC2779108  PMID: 19506139
21.  Prevalence of Mild Cognitive Impairment by Multiple Classifications: The MYHAT Project 
To estimate and compare the frequency and prevalence of mild cognitive impairment (MCI) and related entities using different classification approaches at the population level.
Cross-sectional epidemiologic study of population-based cohort recruited by age-stratified random sampling from electoral rolls.
Small-town communities in western Pennsylvania, USA
Of 2036 individuals aged 65 years and older, 1982 participants with normal or mildly impaired cognition (age-education-corrected Mini-Mental State scores ≥ 21).
Demographics, neuropsychological assessment expressed as cognitive domains, functional ability, subjective reports of cognitive difficulties; based on these measurements, operational criteria for the Clinical Dementia Rating (CDR) scale, the 1999 criteria for Amnestic MCI, the 2004 Expanded criteria for MCI, and new, purely cognitive criteria for MCI.
A CDR rating of 0.5 (questionable dementia) was obtained by 27.6% of participants, while 1.2% had CDR ≥ 1 (mild or moderate dementia). Among those with CDR <1, 2.27% had Amnestic MCI and 17.61% had Expanded MCI, while 34.6 % had MCI by purely cognitive classification. Isolated executive function impairment was the least common, while impairment in multiple domains including executive function was the most common. Prevalence estimates weighted against the US Census are also provided.
The manner in which criteria for MCI are operationalized determines the proportion of individuals who are thus classified, and the degree of overlap with other criteria. Prospective followup is needed to determine progression from MCI to dementia, and thus empirically develop improved MCI criteria with good predictive value.
PMCID: PMC2906673  PMID: 20220597
MCI criteria; subjective memory; epidemiology
In the community at large, many older adults with minimal cognitive and functional impairment remain stable or improve over time, unlike patients in clinical research settings, who typically progress to dementia. Within a prospective population-based study, we identified neuropsychological tests predicting improvement or worsening over one year in cognitively-driven everyday functioning as measured by Clinical Dementia Rating (CDR). Participants were 1682 adults aged 65+ and dementia-free at baseline. CDR change was modeled as a function of baseline test scores, adjusting for demographics. Among those with baseline CDR=0.5, 29.8% improved to CDR=0; they had significantly better baseline scores on most tests. In a stepwise multiple logistic regression model, tests which remained independently associated with subsequent CDR improvement were Category Fluency, a modified Token Test, and the sum of learning trials on Object Memory Evaluation. In contrast, only 7.1% with baseline CDR=0 worsened to CDR=0.5. They had significantly lower baseline scores on most tests. In multiple regression analyses, only the Mini-Mental State Exam, delayed memory for visual reproduction, and recall susceptible to proactive interference, were independently associated with CDR worsening. At the population level, changes in both directions are observable in functional status, with different neuropsychological measures predicting the direction of change.
PMCID: PMC3232179  PMID: 20609270
Epidemiology; community; aging; Clinical Dementia Rating; cognition; prediction
23.  Clinical Prediction of Alzheimer Disease Dementia Across the Spectrum of Mild Cognitive Impairment 
Archives of general psychiatry  2007;64(12):1443-1450.
To determine whether clinical assessment methods that grade the severity of impairments within the spectrum of mild cognitive impairment (MCI) can predict clinical course, particularly among very mildly impaired individuals who do not meet formal MCI criteria as implemented in clinical trials.
Community volunteers.
From a longitudinal study of normal (Clinical Dementia Rating [CDR]=0; n=77) and mildly impaired (CDR=0.5; n=167) participants with 5 or more annual clinical assessments, baseline level of cognitive impairment in daily life was graded using CDR sum of boxes (CDR-SB) and level of cognitive performance impairment was graded using neuropsychological test scores.
Main Outcome Measures:
Five-year outcome measures included (1) probable Alzheimer disease (AD) diagnosis and (2) clinical “decline” (CDR-SB increase ≥1.0). Logistic regression models were used to assess the ability of baseline measures to predict outcomes in the full sample and separately in the subjects who did not meet formal MCI criteria as implemented in a multicenter clinical trial (n = 125; “very mild cognitive impairment” [vMCI]).
The presence of both higher CDR-SB and lower verbal memory and executive function at baseline predicted greater likelihood of probable AD and decline. Five-year rates of probable AD and decline in vMCI (20%, AD; 49%, decline) were intermediate between normal participants (0%, AD; 28%, decline) and participants with MCI (41%, AD; 62%, decline). Within vMCI, likelihood of probable AD was predicted by higher CDR-SB and lower executive function.
Even in very mildly impaired individuals who do not meet strict MCI criteria as implemented in clinical trials, the degree of cognitive impairment in daily life and performance on neuropsychological testing predict likelihood of an AD diagnosis within 5 years. The clinical determination of relative severity of impairment along the spectrum of MCI may be valuable for trials of putative disease-modifying compounds, particularly as target populations are broadened to include less impaired individuals.
PMCID: PMC2581771  PMID: 18056553
24.  The Fate of the 0.5s: Predictors of 2-Year Outcome in Mild Cognitive Impairment 
Impairments in executive cognition (EC) may be predictive of incident dementia in patients with mild cognitive impairment (MCI). The present study examined whether specific EC tests could predict which MCI individuals progress from a Dementia Rating Scale (CDR) score of 0.5 to a score ≥1 over a 2-year period. Eighteen clinical and experimental EC measures were administered at baseline to 104 MCI patients (amnestic and non-amnestic, single- and multiple-domain) recruited from clinical and research settings. Demographic characteristics, screening cognitive measures and measures of everyday functioning at baseline were also considered as potential predictors. Over the two-year period, 18% of the MCI individuals progressed to CDR≥1, 73.1% remained stable (CDR=0.5), and 4.5% reverted to normal (CDR=0). Multiple-domain MCI participants had higher rates of progression to dementia than single-domain, but amnestic and non-amnestic MCIs had similar rates of conversion. Only three EC measures were predictive of subsequent cognitive and functional decline at the univariate level, but they failed to independently predict progression to dementia after adjusting for demographic, other cognitive characteristics, and measures of everyday functioning. Decline over 2 years was best predicted by informant ratings of subtle functional impairments and lower baseline scores on memory, category fluency and constructional praxis.
PMCID: PMC3078700  PMID: 21205413
Mild cognitive impairment; dementia; predictors of decline; executive cognition; Clinical Dementia Rating scale; MCI outcome
25.  Validation of the New Interpretive Guidelines for the Clinical Dementia Rating Scale Sum of Boxes Score in the NACC Database 
Archives of neurology  2010;67(6):746-749.
It was recently demonstrated that the Clinical Dementia Rating scale (CDR) Sum of Boxes (CDR-SB) score can be used to accurately stage severity of Alzheimer’s dementia (AD) and Mild Cognitive Impairment (MCI)1. However, to date, the utility of those interpretive guidelines has not been cross-validated or applied to a heterogeneous sample of dementia cases. This study sought to cross-validate the staging guidelines proposed by those authors utilizing the National Alzheimer’s Coordinating Center (NACC) database.
There were 12,462 participants (Controls n = 5,115, MCI n = 2,551, dementia all etiologies n = 4796) in the NACC dataset utilized for the current analysis. The previously published cut-scores were applied to the NACC sample and diagnostic accuracy estimates obtained. Next, analyses were restricted to NACC participants with CDR-Global Score (CDR-GS) of 0.5 and ROC curves generated to determine optimal CDR-SB cut-scores for distinguishing MCI from very early dementia.
The previously proposed CDR-SB ranges successfully classified the vast majority of patients across all impairment ranges with a κ of 0.91 and 94% overall correct classification rate. Additionally, the CDR-SB score discriminated between patients diagnosed with MCI and dementia when CDR-GS were restricted to 0.5 (overall AUC = 0.83).
These findings cross-validate the previously published CDR-SB interpretative guidelines for staging dementia severity and extend those findings to a large heterogeneous sample of patients with dementia. Additionally, the CDR-SB scores distinguished MCI from dementia in patients with reasonable accuracy when CDR-GS is restricted to 0.5.
PMCID: PMC2888493  PMID: 20558394

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