4.7 Article

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

Journal

NEUROLOGY
Volume 90, Issue 14, Pages E1248-+

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000005259

Keywords

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Funding

  1. National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN26820 1100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
  2. NHLBI [R01-HL70825]
  3. National Institute on Aging [R01AG040282]
  4. [R01-AG053938]
  5. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007055, U01HL096812, U01HL096917, U01HL096814, U01HL096902] Funding Source: NIH RePORTER
  6. NATIONAL INSTITUTE ON AGING [P30AG049638, K99AG052830, R01AG053938, R01AG040282] Funding Source: NIH RePORTER

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Objective Arterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar beta-amyloid (A beta) 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 A beta imaging using florbetapir ([F-18]-AV-45) to obtain standardized uptake volume ratios and defined global A beta-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 A beta deposition adjusted for age, body mass index, sex, race, and APOE epsilon 4 status. We examined the cross-sectional relationships including interactions by race, APOE epsilon 4 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 A beta 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 mm(3), beta = -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 A beta-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 epsilon 4 status. Conclusions Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and A beta deposition.

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