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

Neurology. 2018 Apr 3;90(14):e1248-e1256. doi: 10.1212/WNL.0000000000005259. Epub 2018 Mar 16.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Amyloid beta-Peptides / metabolism
  • Apolipoprotein E4 / genetics
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / epidemiology
  • Atherosclerosis / genetics
  • Atherosclerosis / physiopathology
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Cerebrovascular Disorders / diagnostic imaging
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / physiopathology
  • Cognition
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / epidemiology*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / physiopathology
  • Cohort Studies
  • Cross-Sectional Studies
  • Dementia / diagnostic imaging*
  • Dementia / epidemiology*
  • Dementia / genetics
  • Dementia / physiopathology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Positron-Emission Tomography
  • Risk
  • Risk Factors
  • Vascular Stiffness*


  • Amyloid beta-Peptides
  • Apolipoprotein E4