A Connection between Cognitive Decline and Metabolic Disease May Vary by Sex and Ethnicity

Nancy West, PhD is an Assistant Professor in the Department of Preventive Medicine, School of Population Health at the University of Mississippi Medical Center. Dr. West’s research, published in Age & Ageing, focuses on identifying risk factors for cognitive decline and dementia that will identify high-risk populations and lead to strategies for prevention.

brainDecline in cognitive function in late adulthood has been associated with an interesting cluster of metabolic abnormalities, such as diabetes and obesity. This suggests the possibility that genetic factors that are related to metabolic disease may also be related to cognitive decline. The peroxisome proliferator-activated receptor gamma (PPARG) gene is known to play key roles in fat and glucose metabolism. In our study, we investigated a common mutation in the PPARG gene (Pro12Ala) to determine its relationship with cognitive decline.

We examined the change in cognitive test scores between the start of the study and after 22 months of follow-up among a group of Mexican-Americans and non-Hispanic whites, who were aged 60 years and older. We observed significantly greater decline in the cognitive test score among Hispanic male carriers of the PPARG gene variant compared to Hispanic males without the gene variant. However, we did not observe a difference in rate of decline among female or among non-Hispanic white carriers and non-carriers of the gene variant. Interestingly, another study of older Mexican-Americans also showed the same association between male carriers of the PPARG gene variant and cognitive impairment, while no link was seen among the females. Whether this male-specific association between carriers of the PPARG gene variant and worsening cognitive performance in older adults is a phenomenon across other race/ethnic populations will require additional study.

Read the full Age & Ageing article ‘Cognitive decline and the PPAR-γ Pro12Ala genotype: variation by sex and ethnicity

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