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Brain Aging and APOE ?4 Interact to Reveal Potential Neuronal Compensation in Healthy Older Adults.

ABSTRACT: Compensation implies the recruitment of additional neuronal resources to prevent the detrimental effect of age-related neuronal decline on cognition. Recently suggested statistical models comprise behavioral performance, brain activation, and measures related to aging- or disease-specific pathological burden to characterize compensation. Higher chronological age as well as the APOE ?4 allele are risk factors for Alzheimer's disease. A more biological approach to characterize aging compared with chronological age is the brain age gap estimation (BrainAGE), taking into account structural brain characteristics. We utilized this estimate in an fMRI experiment together with APOE variant as measures related to pathological burden and aimed at identifying compensatory regions during working memory (WM) processing in a group of 34 healthy older adults. According to published compensation criteria, better performance along with increased brain activation would indicate successful compensation. We examined the moderating effects of BrainAGE on the relationship between task performance and brain activation in prefrontal cortex, as previous studies suggest predominantly frontal compensatory activation. Then we statistically compared them to the effects of chronological age (CA) tested in a previous study. Moreover, we examined the effects of adding APOE variant as a further moderator. Herewith, we strived to uncover neuronal compensation in healthy older adults at risk for neurodegenerative disease. Higher BrainAGE alone was not associated with an increased recruitment in prefrontal cortex. When adding APOE variant as a second moderator, we found an interaction of BrainAGE and APOE variant, such that ?4 carriers recruited right inferior frontal gyrus with higher BrainAGE to maintain WM performance, thus showing a pattern compatible with successful neuronal compensation. Exploratory analyses yielded similar patterns in left inferior and bilateral middle frontal gyrus. These results contrast those from a previous study, where we found no indication of compensation in prefrontal cortex in ?4 carriers with increasing CA. We conclude that BrainAGE together with APOE variant can help to reveal potential neuronal compensation in healthy older adults. Previous results on neuronal compensation in frontal areas corroborate our findings. Compensatory brain regions could be targeted in affected individuals by training or stimulation protocols to maintain cognitive functioning as long as possible.

SUBMITTER: Scheller E

PROVIDER: S-EPMC5869204 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Brain Aging and APOE ε4 Interact to Reveal Potential Neuronal Compensation in Healthy Older Adults.

Scheller Elisa E Schumacher Lena V LV Peter Jessica J Lahr Jacob J Wehrle Julius J Kaller Christoph P CP Gaser Christian C Klöppel Stefan S

Frontiers in aging neuroscience 20180320

Compensation implies the recruitment of additional neuronal resources to prevent the detrimental effect of age-related neuronal decline on cognition. Recently suggested statistical models comprise behavioral performance, brain activation, and measures related to aging- or disease-specific pathological burden to characterize compensation. Higher chronological age as well as the APOE ε4 allele are risk factors for Alzheimer's disease. A more biological approach to characterize aging compared with ...[more]

PMID: 29615896

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Project description:IntroductionAdvanced age is a significant factor in changes to brain physiology and cognitive functions. Recent research has highlighted the critical role of the gut microbiome in modulating brain functions during aging, which can be influenced by various factors such as apolipoprotein E (APOE) genetic variance, body mass index (BMI), diabetes, and dietary intake. However, the associations between the gut microbiome and these factors, as well as brain structural, vascular, and metabolic imaging markers, have not been well explored.MethodsWe recruited 30 community dwelling older adults between age 55-85 in Kentucky. We collected the medical history from the electronic health record as well as the Dietary Screener Questionnaire. We performed APOE genotyping with an oral swab, gut microbiome analysis using metagenomics sequencing, and brain structural, vascular, and metabolic imaging using MRI.ResultsIndividuals with APOE e2 and APOE e4 genotypes had distinct microbiota composition, and higher level of pro-inflammatory microbiota were associated higher BMI and diabetes. In contrast, calcium- and vegetable-rich diets were associated with microbiota that produced short chain fatty acids leading to an anti-inflammatory state. We also found that important gut microbial butyrate producers were correlated with the volume of the thalamus and corpus callosum, which are regions of the brain responsible for relaying and processing information. Additionally, putative proinflammatory species were negatively correlated with GABA production, an inhibitory neurotransmitter. Furthermore, we observed that the relative abundance of bacteria from the family Eggerthellaceae, equol producers, was correlated with white matter integrity in tracts connecting the brain regions related to language, memory, and learning.DiscussionThese findings highlight the importance of gut microbiome association with brain health in aging population and could have important implications aimed at optimizing healthy brain aging through precision prebiotic, probiotic or dietary interventions.

Project description:Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern.To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies.Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years.Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death.Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses.Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (??=?0.16; P?=?.02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (??1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (??=?-0.69 score units [95% CI, -1.34 to -0.04]), less severe and widespread neurofibrillary tangles (??=?-0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (??=?-0.53 score units [95% CI, -0.96 to -0.10]) but only among apolipoprotein E (APOE ?4) carriers. Higher intake levels of ?-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology.In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.

Dataset Information

Brain Aging and APOE ?4 Interact to Reveal Potential Neuronal Compensation in Healthy Older Adults.

Publications

Brain Aging and APOE ε4 Interact to Reveal Potential Neuronal Compensation in Healthy Older Adults.

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