Premium
F5‐01‐02: Impact of caloric restriction and caloric restriction‐mimetics on brain structure and function in older adults and patients with mild cognitive impairment
Author(s) -
Flöel Agnes,
Witte Veronica A.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.07.424
Subject(s) - caloric theory , resveratrol , placebo , hippocampus , medicine , prefrontal cortex , hippocampal formation , effects of sleep deprivation on cognitive performance , cognition , endocrinology , psychiatry , pathology , pharmacology , alternative medicine
overview of these findings. Animals in this study were part of the longitudinal “Dietary Restriction and Aging Study” at theWisconsin National Primate Research Center (WNPRC). Animals were either fed a normal diet or maintained on a moderately restricted diet (approximately 30% reduced intake from baseline), with both groups receiving comparable diet supplements. Results: Using volumetric imaging we demonstrated that CR preserves gray matter cortex in limbic and heteromodal association areas, indicating a positive effect of CR against age-related brain atrophy. Diffusion tensor imaging showed preservation of white matter integrity in the corpus callosum and fronto-occipital fasciculus, superior longitudinal fasciculus, external capsule, and brainstem. CR also attenuated age-related iron accumulation in the basal ganglia, red nucleus, and parietal, temporal, and perirhinal cortex. Decreased iron accumulation was in turn associated with faster performance on fine motor function tests, signifying a protective effect against motor slowness that results during aging. CR moderated the effect of important plasma-based inflammatory markers (e.g. IL-6) on gray and white matter changes in several brain areas, including the parietal and temporal graymatter regions that are sensitive to aging. CR improved glucoregulatory profiles and positively influenced gray matter volume in the hippocampus. Histopathology studies reveal that CR monkeys express significantly lower (w30%) levels ofmicroglial activation in the hippocampus. Energy metabolism in the hippocampus as indexed by PGC1alpha and GSK3B was preserved in CR. Number of MTL amyloid plaques was however equivalent between groups. Conclusions: Overall, these results recapitulate the neuroprotective effects of CR from lower animal models. Taken together, these findings point to an overall beneficial effect of CR on the brain in this non-human primate model of aging.