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Background: We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD)., Methods: Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses., Results: APOE ε4 was inversely associated with most cognitive measures (p < 0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (β ε4×age  = -0.44, p = 0.03), orientation (β ε4×age  = -0.07, p = 0.01), and language/fluency (β ε4×age  = -0.07, p = 0.01), as well as in females for memory (β ε4×male  = 0.17, p = 0.02) and language/fluency (β ε4×male  = 0.12, p = 0.03)., Discussion: APOE ε4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals., Highlights: APOE ε4 carriers had lower global and domain-specific cognitive performance. Females and older individuals may be more susceptible to ε4 effects. For most cognitive measures, there was no interaction between ε4 and education., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia., (© 2023. The Author(s).)

Background/objectives: Genetic factors play an important role in Alzheimer's disease (AD) and cognitive aging. However, it is unclear whether risk loci identified in European ancestry (EA) populations have similar effects in other groups, such as South Asians., Design: We investigated the allelic distribution and cognitive associations of 56 known AD risk single-nucleotide polymorphisms (SNPs) identified from three EA genome-wide association studies (EA-GWASs) in a South Asian population. Single SNP and genetic risk score (GRS) associations with measures of episodic memory were assessed., Setting: The Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD)., Participants: A total of 906 LASI-DAD participants from diverse states in India., Measurements: Participants were genotyped using the Illumina Global Screening Array and imputed with 1000G Phase 3v5. Cognitive measures included total learning and delayed word recall., Results: Although only a few SNPs were significantly associated with memory scores (P < .05), effect estimates from the EA-GWAS and the LASI-DAD showed moderate correlation (0.35-0.88) in the expected direction. GRSs were also associated with memory scores, although percentage variation explained was small (0.1%-0.6%)., Conclusions: Discrepancies in allele frequencies and cognitive association results suggest that genetic factors found predominantly through EA-GWASs may play a limited role in South Asians. However, the extent of differences in the genetic architecture of AD and cognition in EA and South Asians remains uncertain. There is also a critical need to perform a more comprehensive assessment of the mutational spectrum of South Asia to identify novel genetic variants associated with AD and cognition in this population. J Am Geriatr Soc 68:S45-S53, 2020., (© 2020 The American Geriatrics Society.)