Who Benefited Most from the Internet-Based Conversational Engagement RCT (I-CONECT)? Application of the Personalized Medicine Approach to a Behavioral Intervention Study.

BACKGROUND: Many Alzheimer's Disease (AD) clinical trials have failed to demonstrate treatment efficacy on cognition. It is conceivable that a complex disease like AD may not have the same treatment effect due to many heterogeneities of disease processes and individual traits. OBJECTIVES: We employed an individual-level treatment response (ITR) approach to determine the characteristics of treatment responders and estimated time saved in cognitive decline using the Internet-based Conversational Engagement Clinical Trial (I-CONECT) behavioral intervention study as a model. DESIGN AND SETTING: I-CONECT is a multi-site, single-blind, randomized controlled trial aimed to improve cognitive functions through frequent conversational interactions via internet/webcam. The experimental group engaged in video chats with study staff 4 times/week for 6 months; the control group received weekly 10-minute check-in phone calls. PARTICIPANTS: Out of 186 randomized participants, current study used 139 participants with complete information on both baseline and 6-month follow-up (73 with mild cognitive impairment (MCI), 66 with normal cognition; 64 in the experimental group, and 75 in the control group). MEASUREMENTS: ITR scores were generated for the Montreal Cognitive Assessment (MoCA) (global cognition, primary outcome) and Category Fluency Animals (CFA) (semantic fluency, secondary outcome) that showed significant efficacy in the trial. ITR scores were generated through 300 iterations of 3-fold cross-validated random forest models. The average treatment difference (ATD) curve and the area between the curves (ABC) were estimated to measure the heterogeneity of treatment responses. Responder traits were identified using SHapley Additive exPlanations (SHAP) and decision tree models. The time saved in cognitive decline was explored to gauge clinical meaningfulness. RESULTS: ABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. Age, cognitive status, time spent with family and friends, education, and personality were important characteristics that influenced treatment responses. Intervention group participants in the upper 30% of ITR scores demonstrated potential delays of 3 months in semantic fluency (CFA) and 6 months in global cognition (MoCA), assuming a 5-fold faster natural cognitive decline compared to the control group during the post-treatment period. CONCLUSIONS: ITR-based analyses are valuable in profiling treatment responders for features that can inform future trial design and clinical practice. Reliably measuring time saved in cognitive decline is an area of ongoing research to gain insight into the clinical meaningfulness of treatment.

Predicting Progression from Normal to MCI and from MCI to AD Using Clinical Variables in the National Alzheimer's Coordinating Center Uniform Data Set Version 3: Application of Machine Learning Models and a Probability Calculator.

Clinical trials are increasingly focused on pre-manifest and early Alzheimer's disease (AD). Accurately predicting clinical progressions from normal to MCI or from MCI to dementia/AD versus non-progression is challenging. Accurate identification of symptomatic progressors is important to avoid unnecessary treatment and improve trial efficiency. Due to large inter-individual variability, biomarker positivity and comorbidity information are often insufficient to identify those destined to have symptomatic progressions. Using only clinical variables, we aimed to predict clinical progressions, estimating probabilities of progressions with a small set of variables selected by machine learning approaches. This work updates our previous work that was applied to the National Alzheimer's Coordinating Center (NACC) Uniform Data Set Version 2 (V2), by using the most recent version (V3) with additional analyses. We generated a user-friendly conversion probability calculator which can be used for effectively pre-screening trial participants.

The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project.

BACKGROUND: Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. OBJECTIVE: To correlate measures of cerebral vascular pathology with cognitive trajectories. SETTING: Observational study. PARTICIPANTS: A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. MEASUREMENTS: For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. RESULTS: A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. CONCLUSION: Indicators of cerebral vascular pathology act differently on late life cognition.

Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures.

OBJECTIVE: White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify 'WM at risk', or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. METHODS: Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. RESULTS: CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. CONCLUSIONS: A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.

The Statistical Modeling of Aging and Risk of Transition Project: Data Collection and Harmonization Across 11 Longitudinal Cohort Studies of Aging, Cognition, and Dementia.

Longitudinal cognitive trajectories and other factors associated with mixed neuropathologies (such as Alzheimer's disease with co-occurring cerebrovascular disease) remain incompletely understood, despite being the rule and not the exception in older populations. The Statistical Modeling of Aging and Risk of Transition study (SMART) is a consortium of 11 different high-quality longitudinal studies of aging and cognition (N=11,541 participants) established for the purpose of characterizing risk and protective factors associated with subtypes of age-associated mixed neuropathologies (N=3,001 autopsies). While brain donation was not required for participation in all SMART cohorts, most achieved substantial autopsy rates (i.e., > 50%). Moreover, the studies comprising SMART have large numbers of participants who were followed from intact cognition and transitioned to cognitive impairment and dementia, as well as participants who remained cognitively intact until death. These data provide an exciting opportunity to apply sophisticated statistical methods, like Markov processes, that require large, well-characterized samples. Thus, SMART will serve as an important resource for the field of mixed dementia epidemiology and neuropathology.

Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study.

BACKGROUND: The APOE*E4 allele of the gene for apolipoprotein E (APOE) has been reported as a risk factor for Alzheimer disease (AD) to varying degrees in different ethnic groups. OBJECTIVE: To compare APOE*E4-AD epidemiological associations in India and the United States in a cross-national epidemiological study. DESIGN: Case-control design within 2 cohort studies, using standardized cognitive screening and clinical evaluation to identify AD and other dementias and polymerase chain reaction to identify APOE genotyping. PARTICIPANTS: Rural community samples, aged 55 years or older (n=4450) in Ballabgarh, India, and 70 years or older (n=886) in the Monongahela Valley region of southwestern Pennsylvania. MAIN OUTCOME MEASURES: Criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable and possible AD and Clinical Dementia Rating (CDR) scale for dementia staging. RESULTS: Frequency of APOE*E4 was significantly lower (P<.001) in Ballabgarh vs the Monongahela Valley (0.07 vs 0.11). Frequency of probable or possible AD, with CDR of at least 1.0, in the Indian vs US samples, was as follows: aged 55 to 69 years, 0.1% (Indian sample only); aged 70 to 79 years, 0.7% vs 3.1%; aged 80 years or older, 4.0% vs 15.7%. Among those aged 70 years or older, adjusted odds ratios (95% confidence interval) for AD among carriers of APOE*E4 vs noncarriers were 3.4 (1.2-9.3) and 2.3 (1.3-4.0) in the Indian and US samples, respectively, and not significantly different between cohorts (P=. 20). CONCLUSION: This first report of APOE*E4 and AD from the Indian subcontinent shows very low prevalence of AD in Ballabgarh, India, but association of APOE*E4 with AD at similar strength in Indian and US samples. Arch Neurol. 2000.

Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project.

OBJECTIVE: To determine incidence rates by age, sex, and education of overall dementia and probable/ possible AD in a largely rural community. METHODS: Ten-year prospective study of a randomly selected community sample aged 65+; biennial cognitive screening followed by standardized clinical evaluation. Incidence rates were estimated for overall dementia (Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised, criteria and Clinical Dementia Rating [CDR]) and for probable/possible AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). RESULTS: The cohort consisted of 1,298 individuals free of dementia at study entry. Among these, 199 incident (new) cases of overall (all-cause) dementia with CDR stage > or = 0.5, including 110 with CDR > or = 1, were detected during follow-up. Among the incident cases, 153 (76.9%) had probable/ possible AD. Age-specific incidence rates are reported for all dementia and for probable/possible AD, by sex and CDR stage. Among all-cause dementias with CDR = 0.5, controlling for age and education, men had a higher incidence rate than women. In the same group, those with less than high school education had significantly higher incidence rates than those with more education. Rates did not vary significantly by sex or education for probable/possible AD or for dementia with CDR > or = 1. CONCLUSIONS: Incidence rates of all dementias and of AD increased with age; men and those with lesser education had higher rates of possible/incipient dementia (CDR = 0.5) in this community. Potential explanations for these sex and education effects are discussed.

Small head size is related to low Mini-Mental State Examination scores in a community sample of nondemented older adults.

The objective of this analysis was to determine the relationship, if any, of head size to performance on a cognitive screening test among elderly nondemented adults participating in a community-based survey. The study sample included 825 subjects (533 women, 292 men), age 70 to 95 years. Multivariate analyses, with adjustment for age and education, revealed that smaller head size was associated with low Mini-Mental State Examination (MMSE) scores (i.e., below the 10th percentile) in both men and women. For every 1-centimeter increment in head size, there was a corresponding reduction of approximately 20% in the probability of a low MMSE score.

Incidence of Alzheimer's disease in a rural community in India: the Indo-US study.

OBJECTIVE: To determine overall and age-specific incidence rates of AD in a rural, population-based cohort in Ballabgarh, India, and to compare them with those of a reference US population in the Monongahela Valley of Pennsylvania. METHODS: A 2-year, prospective, epidemiologic study of subjects aged > or =55 years utilizing repeated cognitive and functional ability screening, followed by standardized clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for the diagnosis, and the Clinical Dementia Rating scale for the staging, of dementia and AD. RESULTS: Incidence rates per 1000 person-years for AD with CDR > or =0.5 were 3.24 (95% CI: 1.48-6.14) for those aged > or =65 years and 1.74 (95% CI: 0.84-3.20) for those aged > or =55 years. Standardized against the age distribution of the 1990 US Census, the overall incidence rate in those aged > or =65 years was 4.7 per 1000 person-years, substantially lower than the corresponding rate of 17.5 per 1000 person-years in the Monongahela Valley. CONCLUSION: These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow-up, cultural factors, and other potential confounders suggest caution in interpreting this finding.

Random versus volunteer selection for a community-based study.

BACKGROUND: Selection methods vary greatly in ease and cost-effectiveness. The effects of selection factors associated with subjects' recruitment into studies can introduce bias and seriously limit the generalizability of results. METHODS: For an epidemiologic study, we recruited an age-stratified random sample of 1,422 community-dwelling individuals aged 65+ years from the voter registration lists in a rural area of southwestern Pennsylvania. The first 1,366 of these were accrued through intensive recruitment efforts; the last 56 of them responded to a single mailing. To increase sample size for future risk factor analyses, we also recruited by direct advertisement a sample of 259 volunteers from the same area. The three groups were compared on selected baseline characteristics and subsequent mortality. RESULTS: The two subgroups of the random sample were not significantly different on any of the variables we examined. Compared to the random sample, in cross-sectional analyses, volunteers were significantly more likely to be women, more educated, and less likely to have used several health and human services. Volunteers also had higher cognitive test scores and Instrumental Activities of Daily Living (IADL) ability. Over 6-8 years (10,861 person-years) of follow-up, volunteers had significantly lower mortality rates than randomly selected subjects. CONCLUSIONS: Health-related studies with populations composed partly or entirely of volunteers should take potential volunteer bias into account when analyzing and interpreting data.

Hypothyroidism and cognition: preliminary evidence for a specific defect in memory.

The effect(s) of hypothyroidism on adult brain cognitive function are poorly understood. We performed a series of neuropsychological tests in 13 thyroid cancer patients while they continued to take their usual dose of levothyroxine (LT4) and again after discontinuing thyroid hormone. Three euthyroid subjects were also tested twice to assess the effect of repeated testing on performance. The tests assessed memory, mood, and attentional resources and controlled for the practice effects of repeated testing. The mean thyrotropin (TSH) on LT4 was 0.56 +/- 0.76 mU/L and while hypothyroid was 69 +/- 33 mU/L. While hypothyroid, the mean Beck depression score was significantly higher (15.31 +/- 9.41 hypothyroid vs. 7.31 +/- 4.82 on LT4) and the subjects rated themselves worse relative to functional memory, concentration, thinking, alertness, and motivation. Hypothyroidism was associated with a decrease in retrieval from memory (p = 0.0034), and this effect could not be attributed to depression or to practice effects. Thyroid state did not affect immediate recall, verbal learning, inhibitory efficiency, information processing speed, or attention switching. Athyrosis is associated with a decrement in delayed recall of verbal information but not in other objective measures of cognition, suggesting that the memory decrement of hypothyroidism is not caused by a generalized reduction in attentional resources.

Movements out of poverty among elderly widows.

Elderly widows are disproportionately in poverty in the United States. However, past research has also shown that a significant number of poor elderly widows do move out of poverty. This work addresses two questions: What are the characteristics of elderly widows who exited from poverty, and what is the magnitude of the increase in income at the time of exit? An event history approach was taken using monthly data from the Survey of Income and Program Participation. Some of the findings are: living with family members is a strong predictor for the transition out of poverty among poor elderly women; those who are permanently impoverished tend to rely solely on food stamps and SSI; elderly widows from poverty with relatively large increases in income; those who exited due to an increase in pension income or gifts had increased their income significantly more than those who exited through other sources.

Sex-role change, anomie and female suicide: a test of alternative Durkheimian explanations.

Durkheim's influential book, Suicide, provides general (economic) anomie, conjugal anomie, and sex-role convergence explanations of changes in suicide rates under conditions of social change. We used trend analyses of American suicide rates and female/male suicide ratios from 1950 to 1984 and the regression of the ratios on female educational attainment, white female labor force participation, white fertility rates, and divorce rates to examine these explanations. The general anomie explanation of female suicide trends is supported for the middle-aged (30 to 54 years) but not for the young (10 to 30 years) or the elderly (55 to 74 years). The conjugal anomie proposition is at best supported for age groups between 15 and 44 when general anomie is not pronounced. The role convergence explanation is rejected for all 13 5-year-age-groups. General anomie may not be a viable explanation of suicide trends for groups actively supporting relevant social changes or not yet tradition-bound or for groups whose retirement status reduces the importance of some social changes.

In-home walking speeds and variability trajectories associated with mild cognitive impairment.

OBJECTIVE: To determine whether unobtrusive long-term in-home assessment of walking speed and its variability can distinguish those with mild cognitive impairment (MCI) from those with intact cognition. METHODS: Walking speed was assessed using passive infrared sensors fixed in series on the ceiling of the homes of elderly individuals participating in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study. Latent trajectory models were used to analyze weekly mean speed and walking speed variability (coefficient of variation [COV]). RESULTS: ISAAC participants living alone included 54 participants with intact cognition, 31 participants with nonamnestic MCI (naMCI), and 8 participants with amnestic MCI at baseline, with a mean follow-up of 2.6 ± 1.0 years. Trajectory models identified 3 distinct trajectories (fast, moderate, and slow) of mean weekly walking speed. Participants with naMCI were more likely to be in the slow speed group than in the fast (p = 0.01) or moderate (p = 0.04) speed groups. For COV, 4 distinct trajectories were identified: group 1, the highest baseline and increasing COV followed by a sharply declining COV; groups 2 and 3, relatively stable COV; and group 4, the lowest baseline and decreasing COV. Participants with naMCI were more likely to be members of either highest or lowest baseline COV groups (groups 1 or 4), possibly representing the trajectory of walking speed variability for early- and late-stage MCI, respectively. CONCLUSION: Walking speed and its daily variability may be an early marker of the development of MCI. These and other real-time measures of function may offer novel ways of detecting transition phases leading to dementia.

Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging.

OBJECTIVE: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders. METHODS: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes. RESULTS: Mean age was 87 ± 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine ω-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine ω-3 pattern and white matter hyperintensity volume. CONCLUSION: Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population.

A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline.

OBJECTIVE: To assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly aged 85 and older. METHODS: Randomized, placebo-controlled, double-blind, 42-month pilot study with 118 cognitively intact subjects randomized to standardized GBE or placebo. Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR) = 0 to CDR = 0.5 and decline in episodic memory function between GBE and placebo groups. RESULTS: In the intention-to-treat analysis, there was no reduced risk of progression to CDR = 0.5 (log-rank test, p = 0.06) among the GBE group. There was no less of a decline in memory function among the GBE group (p = 0.05). In the secondary analysis, where we controlled the medication adherence level, the GBE group had a lower risk of progression from CDR = 0 to CDR = 0.5 (HR = 0.33, p = 0.02), and a smaller decline in memory scores (p = 0.04). There were more ischemic strokes and TIAs in the GBE group (p = 0.01). CONCLUSIONS: In unadjusted analyses, Ginkgo biloba extract (GBE) neither altered the risk of progression from normal to Clinical Dementia Rating (CDR) = 0.5, nor protected against a decline in memory function. Secondary analysis taking into account medication adherence showed a protective effect of GBE on the progression to CDR = 0.5 and memory decline. Results of larger prevention trials taking into account medication adherence may clarify the effectiveness of GBE. More stroke and TIA cases observed among the GBE group requires further study to confirm.

No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.

INTRODUCTION: Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk. METHODS: We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs. RESULTS: Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13). CONCLUSIONS: In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.

Alcohol consumption and cognitive function in late life: a longitudinal community study.

OBJECTIVE: To examine the association between alcohol use and cognitive decline in a longitudinal study of a representative elderly community sample free of dementia at baseline. METHODS: Cognitive functions and self-reported drinking habits were assessed at 2-year intervals over an average of 7 years of follow-up. Cognitive measures, grouped into composites, were examined in association with alcohol consumption. Trajectory analyses identified latent homogeneous groups with respect to alcohol use frequency over time, and their association with average decline over the same period in each cognitive domain. Models controlled for age, sex, education, depression, smoking, general mental status (Mini-Mental State Examination [MMSE]), performance on the given test at baseline, and subsequent new-onset dementia during follow-up. RESULTS: The authors found three homogeneous trajectories that they characterized as no drinking, minimal drinking, and moderate drinking. Few heavy drinkers were identified in this elderly cohort. Compared to no drinking, both minimal and moderate drinking were associated with lesser decline on the MMSE and Trailmaking tests. Minimal drinking was also associated with lesser decline on tests of learning and naming. These associations were more pronounced when comparing current drinkers to former drinkers (quitters) than to lifelong abstainers. CONCLUSION: In a representative elderly cohort over an average of 7 years, a pattern of mild-to-moderate drinking, compared to not drinking, was associated with lesser average decline in cognitive domains over the same period.

Depressive symptoms, cognitive impairment and functional impairment in a rural elderly population in India: a Hindi version of the geriatric depression scale (GDS-H).

OBJECTIVE: To measure depressive symptomatology in a largely illiterate elderly population in India, using a new Hindi version of the Geriatric Depression Scale (GDS-H), and to examine its distribution and associations with age, gender, literacy, cognitive impairment and functional impairment. DESIGN: A Hindi version of the Geriatric Depression Scale was developed and administered to participants along with measures of demographic characteristics, cognitive functioning and functional ability. SETTING: The rural community of Ballabgarh in northern India. PARTICIPANTS: A community sample of 1554 mostly illiterate Hindi-speaking residents of Ballabgarh aged 55+. MEASURES: The Hindi version of the Geriatric Depression Scale (GDS-H); the Hindi Mental State Exam (HMSE); the Everyday Abilities Scale for India (EASI); age, gender and literacy. RESULTS: The GDS-H had high internal consistency and a factor structure comparable to the original English language version. The overall distribution of scores was higher than reported from other populations. Greater numbers of depressive symptoms, as measured by higher scores on the GDS-H, were associated with older age and illiteracy. Among the illiterate, there was no gender difference while among the literate, higher GDS-H scores were found among women. Cognitive impairment and functional disability were independently associated with higher scores on the GDS-H after adjustment for age, gender and literacy. CONCLUSION: A reliable and valid Hindi version of the GDS has been developed. Depressive symptoms as measured by the GDS-H were prominent in this elderly illiterate northern Indian population and strongly associated with both cognitive and functional impairment.