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

Eseosa T. Ighodaro, Erin L. Abner, David W. Fardo, Ai Ling Lin, Yuriko Katsumata, Frederick A. Schmitt, Richard J. Kryscio, Gregory A. Jicha, Janna H. Neltner, Sarah E. Monsell, Walter A. Kukull, Debra K. Moser, Frank Appiah, Adam D. Bachstetter, Linda J. Van Eldik, Peter T. Nelson

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)201-216
Number of pages16
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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    Ighodaro, E. T., Abner, E. L., Fardo, D. W., Lin, A. L., Katsumata, Y., Schmitt, F. A., Kryscio, R. J., Jicha, G. A., Neltner, J. H., Monsell, S. E., Kukull, W. A., Moser, D. K., Appiah, F., Bachstetter, A. D., Van Eldik, L. J., & Nelson, P. T. (2017). Risk factors and global cognitive status related to brain arteriolosclerosis in elderly individuals. Journal of Cerebral Blood Flow and Metabolism, 37(1), 201-216. https://doi.org/10.1177/0271678X15621574