Arterial stiffness and dementia pathology

Atherosclerosis Risk in Communities (ARIC)-PET Study

Timothy M. Hughes, Lynne E. Wagenknecht, Suzanne Craft, Akiva Mintz, Gerardo Heiss, Priya Palta, Dean Foster Wong, Yun Zhou, David Knopman, Thomas H. Mosley, Rebecca F Gottesman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)e1248-e1256
JournalNeurology
Volume90
Issue number14
DOIs
StatePublished - Apr 3 2018

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Vascular Stiffness
Cerebral Small Vessel Diseases
Dementia
Atherosclerosis
Pathology
Odds Ratio
Brain
Confidence Intervals
Cognition
Pulse Wave Analysis
Thigh
Amyloid
Alzheimer Disease
Body Mass Index
Cognitive Dysfunction
White Matter
florbetapir

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Arterial stiffness and dementia pathology : Atherosclerosis Risk in Communities (ARIC)-PET Study. / Hughes, Timothy M.; Wagenknecht, Lynne E.; Craft, Suzanne; Mintz, Akiva; Heiss, Gerardo; Palta, Priya; Wong, Dean Foster; Zhou, Yun; Knopman, David; Mosley, Thomas H.; Gottesman, Rebecca F.

In: Neurology, Vol. 90, No. 14, 03.04.2018, p. e1248-e1256.

Research output: Contribution to journalArticle

Hughes, TM, Wagenknecht, LE, Craft, S, Mintz, A, Heiss, G, Palta, P, Wong, DF, Zhou, Y, Knopman, D, Mosley, TH & Gottesman, RF 2018, 'Arterial stiffness and dementia pathology: Atherosclerosis Risk in Communities (ARIC)-PET Study', Neurology, vol. 90, no. 14, pp. e1248-e1256. https://doi.org/10.1212/WNL.0000000000005259
Hughes TM, Wagenknecht LE, Craft S, Mintz A, Heiss G, Palta P et al. Arterial stiffness and dementia pathology: Atherosclerosis Risk in Communities (ARIC)-PET Study. Neurology. 2018 Apr 3;90(14):e1248-e1256. https://doi.org/10.1212/WNL.0000000000005259
Hughes, Timothy M. ; Wagenknecht, Lynne E. ; Craft, Suzanne ; Mintz, Akiva ; Heiss, Gerardo ; Palta, Priya ; Wong, Dean Foster ; Zhou, Yun ; Knopman, David ; Mosley, Thomas H. ; Gottesman, Rebecca F. / Arterial stiffness and dementia pathology : Atherosclerosis Risk in Communities (ARIC)-PET Study. In: Neurology. 2018 ; Vol. 90, No. 14. pp. e1248-e1256.
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AU - Craft, Suzanne

AU - Mintz, Akiva

AU - Heiss, Gerardo

AU - Palta, Priya

AU - Wong, Dean Foster

AU - Zhou, Yun

AU - Knopman, David

AU - Mosley, Thomas H.

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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 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.

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