Affiliations: [a]
Department of Psychology, University of Southern California, Los Angeles, CA, USA
| [b]
Research Service, Veteran Affairs San Diego Health Care System, San Diego, CA, USA
| [c]
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
| [d] Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA
| [e]
Department of Psychological Science, University of California, Irvine, Irvine, CA, USA
Correspondence:
[*]
Correspondence to: Daniel A. Nation, PhD, Associate Professor, University of California Irvine, Department of Psychological Science, Institute for Memory Impairments and Neurological Disorders, 4201 Social and Behavioral Sciences Gateway, Irvine, CA 92697-7085, USA. Tel.: +1 949 824 9339; Fax: +1 949 824 3002; E-mail: dnation@uci.edu.
Abstract: Background:Blood pressure variability is linked to Alzheimer’s disease (AD) risk and MRI-based markers of cerebrovascular disease. Less is known about the role of blood pressure variability in postmortem evaluation of cerebrovascular disease and AD. Objective:To determine whether antemortem blood pressure variability predicts cerebrovascular and AD pathology and follow-up cognitive change in autopsy-confirmed AD. Methods:National Alzheimer’s Coordinating Center participants (n = 513) underwent 3-4 approximately annual blood pressure measurements and were confirmed to have AD at postmortem evaluation. A subset (n = 493) underwent neuropsychological evaluation at follow-up. Regression models examined relationships between blood pressure variability and cerebrovascular and AD pathological features and follow-up cognitive change. Results:Elevated blood pressure variability predicted increased postmortem cerebrovascular lesion burden (ß = 0.26 [0.10, 0.42]; p = 0.001; R2 = 0.12). Increased blood pressure variability predicted specific cerebrovascular lesion severity, including atherosclerosis in the Circle of Willis (OR = 1.22 [1.03, 1.44]; p = 0.02) and cerebral arteriolosclerosis (OR = 1.32 [1.04, 1.69]; p = 0.03). No significant relationships were observed between blood pressure variability and AD pathological findings, including Braak & Braak stage, neuritic plaques or diffuse plaques, or cerebral amyloid angiopathy, or follow-up cognitive decline. Conclusion:Findings suggest that elevated blood pressure variability is related to postmortem cerebrovascular lesion burden in autopsy-confirmed AD, independent of average blood pressure and AD neuropathology. Blood pressure fluctuation may selectively promote atherosclerotic and arteriolosclerotic brain lesions with potential implications for cognitive impairment and dementia.
