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Title | Risk factors and global cognitive status related to brain arteriolosclerosis in elderly individuals. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Ighodaro ET, Abner EL, Fardo DW, Lin A-L, Katsumata Y, Schmitt FA, Kryscio RJ, Jicha GA, Neltner JH, Monsell SE, Kukull WA, Moser DK, Appiah F, Bachstetter AD, Van Eldik LJ, Nelson PT |
Corporate Authors | Alzheimer's Disease Neuroimaging Initiative(ADNI) |
Journal | J Cereb Blood Flow Metab |
Volume | 37 |
Issue | 1 |
Pagination | 201-216 |
Date Published | 2017 01 |
ISSN | 1559-7016 |
Keywords | Aged, Aged, 80 and over, Aging, Arteriolosclerosis, Brain, Cerebrovascular Circulation, Cognition, Databases, Factual, Genetic Variation, Humans, Hypertension, Risk Factors, Sulfonylurea Receptors |
Abstract | Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological correlations in the "oldest-old" compared to younger cohorts. Therefore, using the National Alzheimer's Coordinating Center data set, we analyzed clinical and neuropathological data from two groups according to ages at death: < 80 years (n = 1008) and ≥80 years (n = 1382). In both age groups, severe brain arteriolosclerosis was associated with worse performances on global cognition tests. Hypertension (but not diabetes) was a brain arteriolosclerosis risk factor in the younger group. In the ≥ 80 years age at death group, an ABCC9 gene variant (rs704180), previously associated with aging-related hippocampal sclerosis, was also associated with brain arteriolosclerosis. A post-hoc arterial spin labeling neuroimaging experiment indicated that ABCC9 genotype is associated with cerebral blood flow impairment; in a convenience sample from Alzheimer's Disease Neuroimaging Initiative (n = 15, homozygous individuals), non-risk genotype carriers showed higher global cerebral blood flow compared to risk genotype carriers. We conclude that brain arteriolosclerosis is associated with altered cognitive status and a novel vascular genetic risk factor. |
DOI | 10.1177/0271678X15621574 |
Alternate Journal | J. Cereb. Blood Flow Metab. |
PubMed ID | 26738751 |
PubMed Central ID | PMC5363738 |
Grant List | P30 AG010124 / AG / NIA NIH HHS / United States K25 AG043546 / AG / NIA NIH HHS / United States F30 NS090714 / NS / NINDS NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States R01 AG042419 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States R01 NR014189 / NR / NINR NIH HHS / United States K01 AG040164 / AG / NIA NIH HHS / United States P30 AG028383 / AG / NIA NIH HHS / United States R21 AG050146 / AG / NIA NIH HHS / United States / / CIHR / Canada |