Aortic Stiffness is Associated with Increased Risk of Incident Dementia in Older Adults

Article type: Research Article

Authors: Cui, Chendi^a | Sekikawa, Akira^a | Kuller, Lewis H.^a | Lopez, Oscar L.^b | Newman, Anne B.^a | Kuipers, Allison L.^a | Mackey, Rachel H.^{a; *}

Affiliations: [a] Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA | [b] Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

Correspondence: [*] Correspondence to: Rachel H. Mackey, PhD, MPH, FAHA, Department of Epidemiology, Graduate School of Public Health, 130 North Bellefield Avenue, Suite 542, Pittsburgh, PA 15213, USA. Tel.: +1 412 624 5948; E-mail: mackey@edc.pitt.edu.

Abstract: Cardiovascular disease risk factors, including age, hypertension, and diabetes, contribute to aortic stiffness and subclinical cardiovascular and brain disease, increasing dementia risk. Aortic stiffness, measured by carotid-femoral pulse wave velocity (cfPWV), reduces the buffering of pulsatile blood flow, exposing cerebral small arteries to microvascular damage. High cfPWV is related to white matter hyperintensities and brain amyloid deposition, and to cognitive decline, but it is unclear whether cfPWV independently predicts incident dementia. Therefore, we tested the hypothesis that cfPWV predicts incident dementia in older adults, independent of potential confounders. The Cardiovascular Health Study Cognition Study followed 532 non-demented older adults with annual cognitive exams from 1998-99 through 2013. CfPWV was measured on 356 (mean age = 78, 59% women) between 1996–2000. Over 15 years, 212 (59.6%) developed dementia (median time from cfPWV measurement = 4 years). In age and sex-adjusted Cox models, cfPWV was significantly associated with increased risk of dementia, but systolic blood pressure, mean arterial pressure and pulse pressure were not. CfPWV (transformed as – 1/cfPWV) remained significantly associated with dementia risk when further adjusted for education, race, APOE ɛ4, diabetes, body mass index, mean arterial pressure, and anti-hypertensive medication (hazard ratio = 1.60, 95% CI = 1.02, 2.51). Results were similar when further adjusted for baseline global cognition, subclinical brain measures, and coronary artery calcification. Finally, higher cfPWV was related to lower physical activity intensity and higher systolic blood pressure, heart rate, and waist circumference measured 5 years prior. An important unanswered question is whether interventions to slow arterial stiffening can reduce the risk of dementia.

Keywords: Dementia, pulse wave velocity, risk factors, vascular stiffness

DOI: 10.3233/JAD-180449

Journal: Journal of Alzheimer's Disease, vol. 66, no. 1, pp. 297-306, 2018