TY - JOUR
T1 - Arterial stiffness and dementia pathology
T2 - Atherosclerosis risk in communities (ARIC)-PET study
AU - Hughes, Timothy M.
AU - Wagenknecht, Lynne E.
AU - Craft, Suzanne
AU - Mintz, Akiva
AU - Heiss, Gerardo
AU - Palta, Priya
AU - Wong, Dean
AU - Zhou, Yun
AU - Knopman, David
AU - Mosley, Thomas H.
AU - Gottesman, Rebecca F.
N1 - Publisher Copyright:
Copyright © 2018 American Academy of Neurology
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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 e4 status. We examined the cross-sectional relationships including interactions by race, APOE e4 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 e4 status. Conclusions Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.
AB - 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 e4 status. We examined the cross-sectional relationships including interactions by race, APOE e4 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 e4 status. Conclusions Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.
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U2 - 10.1212/WNL.0000000000005259
DO - 10.1212/WNL.0000000000005259
M3 - Article
C2 - 29549223
AN - SCOPUS:85048074198
SN - 0028-3878
VL - 90
SP - E1248-E1256
JO - Neurology
JF - Neurology
IS - 14
ER -