Neuroimaging correlates of persistent fatigue in older adults: A secondary analysis from the Multidomain Alzheimer Preventive Trial (MAPT) trial.

OBJECTIVES: Fatigue has been suggested as a marker of biological aging. It seems plausible that this symptom might be associated with changes in brain health. The objective of this study was to examine the associations between persistent fatigue and neuroimaging correlates in a non-disease-specific population of community-dwelling older adults. METHODS: We performed a cross-sectional analysis using data from The Multidomain Alzheimer Preventive Trial (MAPT). We included 458 subjects. Persistent fatigue was defined as meeting exhaustion criterion of Fried frailty phenotype in two consecutive clinical visits six months apart between study baseline and one year. Brain imaging correlates, assessed by magnetic resonance imaging (MRI), were the outcomes. The associations between persistent fatigue and brain correlates were explored using mixed model linear regressions with random effect at the center level. RESULTS: The mean age of the participants was 74.8 ± 4 years old, and 63% of the subjects were women. Forty-seven participants (10%) exhibited a persistent fatigue profile. People with persistent fatigue were older compared to subjects without persistent fatigue (76.2 years ± 4.3 vs.74.7 ± 3.9 p = 0.009). Persistent fatigue was associated with higher white matter hyperintensity volume in the fully adjusted analysis. We did not find any cross-sectional association between persistent fatigue and sub-cortical volumes and global and regional cortical thickness. CONCLUSION: Persistent fatigue was cross-sectionnally associated with higher white matter hyperintensity volume in older adults. Further longitudinal studies, using an assessment tool specifically designed and validated for measuring fatigue, are needed to confirm our findings.

Neuroimaging markers of chronic fatigue in older people: a narrative review.

BACKGROUND: Chronic fatigue is a common symptom in older adults. Although some studies have attempted to identify the neuronal correlates of fatigue associated with chronic diseases, the scientific evidence is scarce regarding fatigue in older people not suffering from a specific disease. AIMS: To gather available evidence of neuroimaging studies investigating the associations between fatigue and brain health in older adults out of the context of a specific disease, and to identify potential brain structures associated with this symptom. METHODS: Studies considering exclusively patients with a specific disease and/or studies focusing on physiological mechanisms of acute fatigue induced by the realization of cognitive and physical tasks were excluded. RESULTS: Very few studies on the associations of fatigue with neuroimaging markers are currently available. Fatigue was associated with reduced hippocampus volumes and with hippocampal amyloid deposition. Regarding the association between fatigue and the circuit of basal ganglia, putamen and thalamus were associated with physical fatigability, whereas amygdala and thalamus with mental fatigability. Very limited evidence about white matter integrity found that healthy individuals with high levels of fatigue had a greater total volume of leukoaraiosis. CONCLUSION: This review suggests that hippocampus damage and potentially loss of function in basal ganglia networks could play a role on chronic fatigue during aging. Further studies are needed to assess the associations of fatigue with white matter alterations.

Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer's disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses.

BACKGROUND: The association between omega-3 (ω-3) PUFAs and cognition, brain imaging and biomarkers is still not fully established. OBJECTIVES: The aim was to analyze the cross-sectional and retrospective longitudinal associations between erythrocyte ω-3 index and cognition, brain imaging, and biomarkers among older adults. METHODS: A total of 832 Alzheimer's Disease Neuroimaging Initiative 3 (ADNI-3) participants, with a mean (SD) age of 74.0 (7.9) y, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment, and 11.4% with Alzheimer disease (AD) were included. A low ω-3 index (%EPA + %DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests [composite score, AD Assessment Scale Cognitive (ADAS-Cog), Wechsler Memory Scale (WMS), Trail Making Test, Category Fluency, Mini-Mental State Examination, Montreal Cognitive Assessment] and brain variables [hippocampal volume, white matter hyperintensities (WMHs), positron emission tomography (PET) amyloid-ß (Aß) and tau] were considered as outcomes in regression models. RESULTS: Low ω-3 index was not associated with cognition, hippocampal, and WMH volume or brain Aß and tau after adjustment for demographics, ApoEε4, cardiovascular disease, BMI, and total intracranial volume in the cross-sectional analysis. In the retrospective analysis, low ω-3 index was associated with greater Aß accumulation (adjusted ß = 0.02; 95% CI: 0.01, 0.03; P = 0.003). The composite cognitive score did not differ between groups; however, low ω-3 index was significantly associated with greater WMS-delayed recall cognitive decline (adjusted ß = -1.18; 95% CI: -2.16, -0.19; P = 0.019), but unexpectedly lower total ADAS-Cog cognitive decline. Low ω-3 index was cross-sectionally associated with lower WMS performance (adjusted ß = -1.81, SE = 0.73, P = 0.014) and higher tau accumulation among ApoE ε4 carriers. CONCLUSIONS: Longitudinally, low ω-3 index was associated with greater Aß accumulation and WMS cognitive decline but unexpectedly with lower total ADAS-Cog cognitive decline. Although no associations were cross-sectionally found in the whole population, low ω-3 index was associated with lower WMS cognition and higher tau accumulation among ApoE ε4 carriers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is registered at clinicaltrials.gov as NCT00106899.

Cross-sectional and longitudinal interaction effects of physical activity and APOE-ε4 on white matter integrity in older adults: The MAPT study.

BACKGROUND: Physical activity (PA) has been shown to modulate the detrimental effect of carrying the apolipoprotein-E epsilon 4 (APOE-ɛ4) allele on brain structure. However, the current literature mainly provides cross-sectional data, and longitudinal studies investigating the interaction between genotype and PA on white matter (WM) integrity are lacking. OBJECTIVES: We investigated both the cross-sectional and the longitudinal interactive effects of APOE-ɛ4 and PA on WM integrity in older adults. METHODS: Fractional anisotropy, as well as axial, radial, and mean diffusivity, extracted from brain diffusion tensor imaging (DTI) were used to assess WM integrity in non-demented older adults. They were categorized according to their APOE-ɛ4 status (carriers vs. non-carriers), and their level of total (TPA), moderate to vigorous (MVPA) and light (LPA) PA were assessed using a questionnaire. Mixed model regressions were performed to test the interactive effects of APOE-ɛ4 status and PA on WM integrity at baseline and over a 3-year follow-up. RESULTS: 190 subjects with a mean age 74.5 years (SD = 3.9) were examined. Despite a lack of cross-sectional associations, sensitivity analyses revealed that, in the carrier group only, higher levels of LPA, but not MVPA, were mainly associated with higher axial and mean diffusivity values over time. CONCLUSIONS: This study partially confirms the previously reported interactive associations between PA, APOE-ɛ4 genotype and WM integrity, supporting the hypothesis that PA may protect against fiber loss in WM tracts containing crossing fibers. Future studies assessing sedentary behaviors in addition to PA could bring relevant contributions to the field. CLINICAL TRIAL REGISTRATION NUMBER FROM CLINICALTRIALS.GOV: NCT00672685.

Meal-related difficulties and weight loss in older people: Longitudinal data from MAPT study.

BACKGROUND: Difficulties with meal-related activities (preparing meals and food shopping) may influence food intake, and contribute to nutritional risk among elderly people. All known studies on this topic had a cross-sectional design, thereby no causal relationships could be derived. We aim to investigate if difficulties with meal-related activities can contribute to subsequent weight loss in community-dwelling older people. METHODS: We used data of older subjects from the MAPT Study (n = 1531, median age = 74 years, 64% women), who provided prospective data on weight every 6 months and cognitive, physical condition, and functional capacities every year during a 3-year period. Difficulties preparing meals and shopping were evaluated each year with the Alzheimer's Disease Cooperative Study-Activities of Daily Living Prevention Instrument (ADCS ADL-PI) Scale. The risk of losing weight (≥5% or ≥ 3 kg in the following year) was estimated using a time-dependent Cox regression model. RESULTS: During the 3-year follow-up, a total of 851 subjects experienced at least a 5% or 3 kg weight loss. Two hundred thirty-seven subjects declared having difficulties with meal preparation at least once, and 133 declared having difficulties shopping. Subjects reporting any meal-related difficulties were older (p < 0.001), had more depressive symptoms (p < 0.001), and a lower physical function (p < 0.001) compared to those without difficulties. They also had a lower cognitive score (preparing meals: p < 0.001; shopping: p = 0.005) and a lower body mass index (preparing meals: p = 0.005; shopping: p = 0.023) at the end of the study. Meal-related activities were not associated with weight loss in unadjusted analysis and after adjustment for sex, age, depression, physical and cognitive status. CONCLUSION: Difficulties preparing meals and shopping had no effect on weight loss in community-dwelling older people, despite their association with advanced age, functional decline, and depressive symptoms.