Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD

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.