Arterial stiffness and dementia pathology: Atherosclerosis Risk in Communities (ARIC)-PET Study

Timothy M. Hughes, Lynne E. Wagenknecht, Suzanne Craft, Akiva Mintz, Gerardo Heiss, Priya Palta, Dean Wong, Yun Zhou, David S Knopman, Thomas H. Mosley, Rebecca F. Gottesman

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30 Scopus citations


OBJECTIVE: Arterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts. METHODS: The Atherosclerosis Risk in Communities (ARIC)-Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([18F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE ε4 status. We examined the cross-sectional relationships including interactions by race, APOE ε4 status, and cognition. RESULTS: Among the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01-1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease-susceptible regions (in mm3, β = -1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2-2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1-2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE ε4 status. CONCLUSIONS: Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.

Original languageEnglish (US)
Pages (from-to)e1248-e1256
Issue number14
StatePublished - Apr 3 2018

ASJC Scopus subject areas

  • Clinical Neurology

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    Hughes, T. M., Wagenknecht, L. E., Craft, S., Mintz, A., Heiss, G., Palta, P., Wong, D., Zhou, Y., Knopman, D. S., Mosley, T. H., & Gottesman, R. F. (2018). Arterial stiffness and dementia pathology: Atherosclerosis Risk in Communities (ARIC)-PET Study. Neurology, 90(14), e1248-e1256.