title: Risk factors and global cognitive status related to brain arteriolosclerosis in elderly individuals.
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.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.|Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Eseosa T
authors.initials: ET
authors.lastname: Ighodaro
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Epidemiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Biostatistics, University of Kentucky, Lexington, KY, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA.|Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, University of Kentucky, Lexington, KY, USA.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Katsumata
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Biostatistics, University of Kentucky, Lexington, KY, USA.|Department of Statistics, University of Kentucky, Lexington, KY, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
authors.forename: Janna H
authors.initials: JH
authors.lastname: Neltner
authors.affiliation: National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Monsell
authors.affiliation: National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
authors.affiliation: College of Nursing, University of Kentucky, Lexington, KY, USA.
authors.forename: Debra K
authors.initials: DK
authors.lastname: Moser
authors.affiliation: Department of Biostatistics, University of Kentucky, Lexington, KY, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Appiah
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Bachstetter
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.|Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA pnels2@email.uky.edu.|Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000523:psychology*; D050379:Arteriolosclerosis / Q000209:etiology* / Q000235:genetics / Q000523:psychology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000235:genetics; D003071:Cognition; D016208:Databases, Factual; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000150:complications; D012307:Risk Factors; D064233:Sulfonylurea Receptors / Q000235:genetics
chemical_list: C577510:ABCC9 protein, human; D064233:Sulfonylurea Receptors
keywords: Arteriosclerosis; CVD; HS-Aging; TDP-43; VCID