Apolipoprotein (APOE4) allele as a predictor for Amygdala structure and Anxiety in normal aging‐ Results from the Triple‐A (Amygdala, Anxiety, and Ageing) study

Abstract

AbstractBackgroundApolipoprotein E4 (APOE4) gene is an important risk factor based on available literature for late onset Alzheimer’s dementia and its effect on normal brain aging in Low and Middle‐income countries has been less studied. The evolutionary benefit that APOE4 confers against various infections during the younger age versus the vulnerability it offers that predisposes to the development of late‐onset cognitive decline is quite exciting but very less studied. We attempt to look into the effects of APOE4 carrier status and its influence on Amygdala structure and as an independent predictor for the development of late‐life anxiety symptoms.MethodThe subjects were recruited from the Tata Longitudinal Study of Ageing (TLSA) cohort, which is an Urban cohort wherein cognitively healthy participants ≥45 years, evaluated for baseline clinical cognitive, genetic, and imaging studies and followed up annually. About 102 participants whose APOE4 genotyping were done were included in this study and compared with their imaging characteristics especially looking into the amygdaloid volumes. Data was analyzed using SPSS v.24ResultMore than half of the participants were females (52%). The APOE4 carrier status (homozygous or heterozygous to APOE4 allele) was present in 51% of the individuals, and only 2.2% of the subjects had overt anxiety symptoms. The mean age of females were 63.89土9.6 and Males 64.82 土 9.3 years, respectively. With normalized imaging data, it was found that males had significantly higher left and right amygdaloid volumes than females(P<0.001) irrespective of the carrier status, and when the Hindi Mental Status Examination (HMSE) scores were considered as an outcome measure, there was a significant reduction in the Right amygdala volumes in the carriers versus non carriers.ConclusionAmygdala is an integral part of the limbic system mediating emotions tagged to cognition, and its structure is likely modulated by the APOE4 carrier status. It could likely impact global cognition even when there is no significant difference in neuropsychological test scores between the carriers and non‐carriers in a cohort of cognitively normal individuals. However, ApoE4 carrier status does not seem to predict anxiety or depression early in cognitively healthy individuals, especially among the Indian population.