Effects of APOE84 genotype on age-associated change in cognitive functions among Japanese middle-aged and older adults: A 20-year follow-up study

Background and aims: Carriers of the apolipoprotein E 84 allele (APOE84) have an increased risk of developing dementia (e.g., Alzheimer's disease). However, it is less clear whether the APOE84 might also be involved in cognitive aging among the non-clinical population of older adults. While some studies have suggested that the APOE84 is related to accelerated cognitive decline in the normal aging process, others have failed to provide compelling evidence of such an impact. Notably, these discrepancies may depend on methodological short-comings, including short time spans, few assessments, and small sample sizes. The present study overcomes the above limitations and aims to clarify the impact of the APOE84 genotype on long-term longitudinal changes in cognitive functions in middle-aged and older adults in Japan.Methods and results: The data were retrieved from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) survey (N = 1832; 40 to 79 years of age at baseline). The participants were tested over nine waves covering a period of approximately 20 years. Latent Growth Curve (LGC) modeling was employed to test the impact of the interaction between APOE84 status and age on several cognitive functions. Four tests of the WAIS-R were administered: Information, Similarities, Picture completion, and Digit Symbol Sub-stitution Test (DSST). The results showed that the APOE84 carriers experienced a more pronounced decline in the DSST (p = 0.001) and Similarities (p = 0.022) tests. A similar tendency was found in the Information test (p = 0.034). By contrast, no effect was found in the Picture completion test (p = 0.563).Conclusions: APOE84 carriers seem to exhibit a steeper cognitive decline, which becomes apparent in old age. This effect is more robust in fluid cognitive skills (DSST) than crystallized cognitive skills (Information and Similarities). Overall, the APOE84 genotype may be a significant risk factor in normal (i.e., non-clinical) cognitive aging.