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

Abstract

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.

Figure. hcPWV as it relates to dementia-related pathology by race

hcPWV (measured in centimeters per second) relates to (A) Aβ deposition (Aβ status, positive or negative, based on SUVR > 1.2) measured by PET; (B) the burden of cerebral small vessel disease (0, 1, and 2 or more forms); and (C) the overlap of common dementia-related pathology, Aβ status, and high WMH volume (high vs low, based on median split) measured by MRI. Shown as means and 95% confidence interval adjusted for age, sex, race, and APOE ε4 status. Aβ = β-amyloid; hcPWV = heart-carotid pulse wave velocity; SUVR = standardized uptake value ratio; WMH = white matter hyperintensity.