Modifiable risk factors for dementia in India: A cross-sectional study revisiting estimates and reassessing prevention potential and priorities.

Background: About 16% of worldwide dementia cases are in India. Evaluating the prospects for dementia prevention in India requires knowledge of context-specific risk factors, as relationships between risk factors and dementia observed in high-income countries (HICs) may not apply.

Methods: We computed population attributable fractions (PAFs) for dementia in India by estimating associations between risk factors and dementia, their prevalence and communality, within the same nationally representative sample of 4,096 Indians aged 60 and older, surveyed through the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD).

Measurement Error and Methodologic Issues in Analyses of the Proportion of Variance Explained in Cognition.

Existing studies examining the predictive ability of biomarkers for cognitive outcomes do not account for variance due to measurement error, which could lead to under-estimates of the proportion of variance explained. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1084) to estimate the proportion of variance explained by Alzheimer's disease (AD) imaging biomarkers in four cognitive outcomes: memory, executive functioning, language, and visuospatial functioning. We compared estimates from standard models that do not account for measurement error, and multilevel models that do account for measurement error.

Development and assessment of analytic methods to improve the measurement of cognition in longitudinal studies of aging through the use of substudies with comprehensive neuropsychological testing.

Introduction: The Health and Retirement Study International Partner Surveys (HRS IPS) have rich longitudinal data, but the brevity of cognitive batteries is a limitation.

Methods: We used data from a substudy of the English Longitudinal Study of Ageing (ELSA) administering detailed cognitive assessments with the Harmonized Cognitive Assessment Protocol (ELSA-HCAP) (N = 1273) to inform approaches for estimating cognition in ELSA (N = 11,213). We compared two novel approaches: confirmatory factor analysis (CFA)- and regression-based prediction.

Considerations for the use of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in cross-country comparisons of cognitive aging and dementia.

Introduction: Informant reports are a critical component of dementia diagnoses, but the comparability of informant reports across countries is not well understood.

Methods: We compared the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) using population-representative surveys in the United States (N = 3183), England (N = 1050), and India (N = 4047).

Results: Analyses of regression splines and comparisons of model fit showed strong associations between IQCODE and objective cognition at low cognitive functioning in the United States and England; in India, the association was weaker but consistent over the range of cognition.

Prevalence of DSM-5 mild and major neurocognitive disorder in India: Results from the LASI-DAD.

Introduction: India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder.

Methods: The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) (N = 4,096) is a nationally representative cohort study in India using multistage area probability sampling methods.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nationwide survey.

Introduction: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over 2 years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context.

Methods: We used data from the Real-Time Insights of COVID-19 in India cohort study (N=3709).

Mental Health Impacts of COVID-19: Does Prepandemic Cognition and Dementia Status Matter?

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted daily life and led to sharp shocks in trends for various health outcomes. Although substantial evidence exists linking the pandemic and mental health outcomes and linking dementia and mental health outcomes, little evidence exists on how cognitive status may alter the impact of COVID-19 on mental health.

Methods: We used prepandemic data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia study and 9 waves of data from the Real-Time Insights of COVID-19 in India study (N = 1 182).

Harmonisation of later-life cognitive function across national contexts: results from the Harmonized Cognitive Assessment Protocols.

Background: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonise general and domain-specific cognitive scores from HCAP studies across six countries, and evaluate reliability and criterion validity of the resulting harmonised scores.

Methods: We statistically harmonised general and domain-specific cognitive function scores across publicly available HCAP partner studies in China, England, India, Mexico, South Africa, and the USA conducted between October, 2015 and January, 2020.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nation-wide survey.

Introduction: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over two years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context.

Methods: We used data from the Real-Time Insights of COVID-19 in India (RTI COVID-India) cohort study (N=3,662).

Harmonization of Later-Life Cognitive Function Across National Contexts: Results from the Harmonized Cognitive Assessment Protocols (HCAPs).

Background: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonize general and domain-specific cognitive scores from HCAPs across six countries, and evaluate precision and criterion validity of the resulting harmonized scores.

Methods: We statistically harmonized general and domain-specific cognitive function across the six publicly available HCAP partner studies in the United States, England, India, Mexico, China, and South Africa (N=21,141).

Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

Introduction: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.

Methods: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs.

The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia.

Background: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population.

Measurement differences in the assessment of functional limitations for cognitive impairment classification across geographic locations.

Introduction: The measurement of dementia in cross-national contexts relies on the assessment of functional limitations. We aimed to evaluate the performance of survey items on functional limitations across culturally diverse geographic settings.

Methods: We used data from the Harmonized Cognitive Assessment Protocol Surveys (HCAP) in five countries (total N = 11,250) to quantify associations between items on functional limitations and cognitive impairment.

Body Mass Index and Cognition: Associations Across Mid- to Late Life and Gender Differences.

Background: Higher mid-life body mass index (BMI) is associated with lower late-life cognition. Associations between later-life BMI and cognition are less consistent; evidence suggests reverse causation may play a role. We aimed to characterize associations between BMI and cognition across a wide age range during mid- to late life (55-85 years) and examine whether associations vary by gender.

The worldwide costs of dementia in 2019.

Introduction: Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components.

Methods: We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs.

AD and non-AD mediators of the pathway between the APOE genotype and cognition.

Introduction: The apolipoprotein E (APOE) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late-life cognition through Alzheimer's disease (AD) and non-AD neuropathologies.

Methods: We analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS/MAP/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (Aβ), neurofibrillary tangles), vascular (athero/arteriolo-sclerosis, micro-infarcts/macro-infarcts), and non-AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP-43], Lewy bodies, amyloid angiopathy, hippocampal sclerosis).

The application of cross-sectionally derived dementia algorithms to longitudinal data in risk factor analyses.

Purpose: Dementia algorithms are often developed in cross-sectional samples but implemented in longitudinal studies to ascertain incident dementia. However, algorithm performance may be higher in cross-sectional settings, and this may impact estimates of risk factor associations.

Methods: We used data from the Religious Orders Study and the Memory and Aging Project (N = 3460) to assess the performance of example algorithms in classifying prevalent dementia in cross-sectional samples versus incident dementia in longitudinal samples.

Sex-specific effects of microglial activation on Alzheimer's disease proteinopathy in older adults.

Females show a disproportionate burden of Alzheimer's disease pathology and higher Alzheimer's disease dementia prevalences compared to males, yet the mechanisms driving these vulnerabilities are unknown. There is sexual dimorphism in immunological functioning, and neuroimmune processes are implicated in Alzheimer's disease genesis. Using neuropathology indicators from human brain tissue, we examined the mediational role of microglial activation on the relationship between amyloid and tau and how it differs by sex.

Performance of the Informant Questionnaire on Cognitive Decline for the Elderly (IQCODE) in a nationally representative study in India: the LASI-DAD study.

Background: Low and middle-income countries like India anticipate rapid population aging and increases in dementia burden. In India, dementia screening scales originally developed in other contexts need to be assessed for feasibility and validity, given the number of different languages and varying levels of literacy and education.

Method: Using data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (N = 4,028), we characterize the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).

Differences in the measurement of cognition for the assessment of dementia across geographic contexts: Recommendations for cross-national research.

Introduction: Most cognitive assessments have been developed in high-income countries but are used in diverse contexts. Differences in culture and context may affect the performance of cognitive items.

Methods: We used the Harmonized Cognitive Assessment Protocol (HCAP) surveys in the United States, Mexico, India, England, and South Africa (combined N = 11,364) to quantify associations across countries between cognitive items and cognitive impairment status using age- and sex-adjusted logistic regression.