Role of diet and genetics on aging brain and cognition

Abstract

<p>Cognitive decline in old age is normative, but decline can be exacerbated in individuals with Alzheimer’s disease (AD) risk factors. Recent studies suggest that certain dietary regimens may slow or exacerbate this decline. However, it is uncertain how changes in whole food consumption affects fluid intelligence (FI) performance, an index of reasoning ability, in adults with or without AD genetic risk over time. Genetic risk for Alzheimer’s disease (AD) is mostly found on Chromosome 19 in the APOE-TOMM40-APOC1 region. Specifically, the Apolipoprotein E ε4 (APOE4) haplotype confers the greatest genetic risk for late-onset Alzheimer’s disease (AD).</p> <p>Food Frequency Questionnaire and Fluid Intelligence Test scores, assessed three times across 6 years, were obtained from UK Biobank to cross-sectionally and longitudinally examine which whole foods were most related to FI. Results indicated that both non-carriers (APOE4-) and especially carriers (APOE4+) showed increased FI with daily cheese and alcohol consumption at baseline. Conversely, decreased FI was seen among APOE4- with daily vegetable consumption over time. Among APOE4+, regular salt use showed worse FI scores over time. Our findings broadly suggest that reducing FI-related cognitive decline may be related to limiting meat, salt, and vegetable consumption, while increasing intake of wheat products, cheese, as well as the consumption of alcohol in moderation. Food recommendations, with AD genetic and family history factors in consideration, may minimize cognitive decline.</p> <p>Translocase of Outer Mitochondrial Membrane-40 (TOMM40) is the only nuclear-encoded gene that controls mitochondrial protein transport, which is critical for maintaining cellular bioenergetics and is progressively disrupted in AD. TOMM40 rs2075650 (‘650) is one of the most consistent loci to show associations with several neural and cognitive outcomes relevant to AD. For example, TOMM40 ‘650 genotypes might affect neural network strength, an early brain marker that is disrupted along the AD continuum. Therefore, 21 orthogonally derived neural networks were examined among 8,222 participants in the UK Biobank cohort. Results indicated that TOMM40 ‘650 G allele may be related to functional connectivity in auditory and language comprehension areas. This relationship may be modified by sex interactions. Differences were observed between G carriers and non-carriers among males, but not females. Not surprisingly, APOE4 was associated with several neural networks that share brain topology generally affected by AD pathology.</p>