Fat-Soluble Nutrients in Serum and Brain of Centenarians and Their Relationship to Neuropathology and Cognition.
Tanprasertsuk, Jirayu.
2019
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Background: Dementia
is a major epidemic in aging societies. Clinico-neuropathological (CP) studies are the
key to identify characteristics associated with aging without dementia. Existing
evidence on CP correlations is very limited in centenarians despite the distinct
pathophysiology of dementia in this age group. An examination of nutritional status in
the brain as a combination of nutrients ... read moreas it relates to brain health has not been
performed. Therefore, the objectives of this study were: Aim1 to establish the CP
relationship to cognition in centenarians; Aim2 to identify which combination of
fat-soluble nutrients in the brain were related to better cognition; Aim3 to investigate
the cross-sectional relationship between brain nutritional status and neuropathology;
Aim4 and to investigate the cross-sectional relationship between serum and brain
nutrient concentrations. Methods: The aims are pursued with data from the Georgia
Centenarian Study (n=49, mean (SD) age 102.2 (2.5) y). Subjects underwent cognitive
assessment and serum collection at enrollment and every 6 months. Only data from the
timepoint closest to death were used. Measures of fat-soluble nutrients in serum and
brain samples included carotenoids, retinol, α- and γ-tocopherols (TP),
phylloquinone (PK), menaquinone-4 (MK-4), and fatty acids (FA). Brain nutrient patterns
(NP) were constructed with principal component analysis using concentrations averaged
from the frontal (FC) and temporal cortices (TC). Potential confounders were controlled
for each analysis of association/correlation. Results: Aim1 Wide ranges of Alzheimer's
disease (AD)-type neuropathological changes were observed in both nondemented and
demented subjects. Neocortical neurofibrillary tangle (NFT) was related to clinical
dementia rating. Neocortical NFT and neuritic plaques, cerebral atrophy, hippocampal
sclerosis, cerebral amyloid angiopathy (CAA), and TDP-43 pathology were differentially
associated with poor cognitive performance in multiple domains. Aim2 Brain NP high in
carotenoids, saturated and n-3 polyunsaturated FAs, and low in monounsaturated FAs was
associated with better performance on global cognition (p=0.048), memory (p=0.063),
language (p=0.035), activities of daily living (p=0.077), and lower depression (p=0.061)
in nondemented subjects. Aim3 Brain α-TP concentrations (averaged from FC, TC,
occipital cortex, cerebellum) were significantly lower among subjects with Braak III-IV
than those with Braak I-II (p=0.032). Brain α-TP was inversely associated with NFT
counts in amygdala (p=0.019), entorhinal cortex (p=0.017), hippocampus (p=0.006), and
subiculum (p=0.008) where NFT present earlier in AD but not neocortices. Docohexaenoic
acid (DHA) was respectively 13.51% (p=0.021) and 21.51% (p=0.037) lower in FC and TC in
subjects with moderate to severe CAA as compared to those with no CAA. Aim4 Serum
carotenoids, α- and γ-TPs, and total n-3 polyunsaturated FAs were correlated
with their FC and TC contents (p<0.05). MK-4 was the most predominant form of vitamin
K in FC (≥89.15%) and TC (≥89.71%) but not correlated with serum PK
levels. Conclusions: AD-type pathology was associated with severe dementia and poor
cognition but not the only variable that explained cognitive impairment in centenarians.
Timing of nutritional intervention is possibly critical since nutritional status in the
brain was associated with better cognition only in nondemented adults, and brain
α-TP was associated with early but not late NFT stages. DHA's association with
cognition may in part be mediated through its association with CAA severity. While brain
concentrations of carotenoids, TPs, and n-3 polyunsaturated FAs may be modulated through
habitual intakes, brain vitamin K level is not solely dependent on its
intake.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Biochemical and Molecular Nutrition.
Advisor: Elizabeth Johnson.
Committee: Tammy Scott, Aron Barbey, Xiang-Dong Wang, and Kathryn Barger.
Keywords: Nutrition, Neurosciences, and Gerontology.read less - ID:
- m613nb15h
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