|Title||Arterial stiffness and dementia pathology: Atherosclerosis Risk in Communities (ARIC)-PET Study.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Hughes TM, Wagenknecht LE, Craft S, Mintz A, Heiss G, Palta P, Wong D, Zhou Y, Knopman D, Mosley TH|
|Secondary Authors||Gottesman RF|
|Date Published||2018 04 03|
|Keywords||Aged, Amyloid beta-Peptides, Apolipoprotein E4, Atherosclerosis, Brain, Cerebrovascular Disorders, Cognition, Cognitive Dysfunction, Cohort Studies, Cross-Sectional Studies, Dementia, Female, Humans, Magnetic Resonance Imaging, Male, Positron-Emission Tomography, Risk, Risk Factors, Vascular Stiffness|
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 ([F]-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 ε4 status. We examined the cross-sectional relationships including interactions by race, ε4 status, and cognition.
RESULTS: Among the 320 ARIC-PET participants (76  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 mm, β = -1.5 [0.7 SD], = 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 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.
|PubMed Central ID||PMC5890613|
|Grant List||F30 ES019463 / ES / NIEHS NIH HHS / United States |
U01 HL096812 / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
R01 AG053938 / AG / NIA NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
R01 AG040282 / AG / NIA NIH HHS / United States
P30 AG049638 / AG / NIA NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
K24 AG052573 / AG / NIA NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
K99 AG052830 / AG / NIA NIH HHS / United States