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J Cereb Blood Flow Metab. 2017 Jan;37(1):201-216. Epub 2016 Jan 6.

Risk factors and global cognitive status related to brain arteriolosclerosis in elderly individuals.

Author information

1
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
2
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
3
Department of Epidemiology, University of Kentucky, Lexington, KY, USA.
4
Department of Biostatistics, University of Kentucky, Lexington, KY, USA.
5
Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA.
6
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
7
Department of Neurology, University of Kentucky, Lexington, KY, USA.
8
Department of Statistics, University of Kentucky, Lexington, KY, USA.
9
Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
10
National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA.
11
Department of Epidemiology, University of Washington, Seattle, WA, USA.
12
College of Nursing, University of Kentucky, Lexington, KY, USA.
13
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA pnels2@email.uky.edu.

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.

KEYWORDS:

Arteriosclerosis; CVD; HS-Aging; TDP-43; VCID

PMID:
26738751
PMCID:
PMC5363738
DOI:
10.1177/0271678X15621574
[Indexed for MEDLINE]
Free PMC Article

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