TY - JOUR
T1 - Brain white matter structure and amyloid deposition in black and white older adults
T2 - The aric-pet study
AU - Walker, Keenan A.
AU - Silverstein, Noah
AU - Zhou, Yun
AU - Hughes, Timothy M.
AU - Jack, Clifford R.
AU - Knopman, David S.
AU - Sharrett, A. Richey
AU - Wong, Dean F.
AU - Mosley, Thomas H.
AU - Gottesman, Rebecca F.
N1 - Funding Information:
The ARIC study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Neurocognitive data are collected by U01 2U01HL 096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the National Institutes of Health (NIH) (NHLBI, National Institute of Neurological Disorders and Stroke [NINDS], National Institute on Aging [NIA], and National Institute on Deafness and Other Communication Disorders [NIDCD]), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. The ARIC-PET study is funded by the NIA (R01AG040282). Infrastructure was partly supported by grant number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This study was also supported by contracts K23 AG064122 (Dr Walker) and K24 AG052573 (Dr Gottesman) from the NIA. This research was supported in part by the Intramural Research Program of the NIH/NIA. Avid Radiopharmaceuticals provided the florbetapir isotope for the study but had no role in the study design or interpretation of results.
Funding Information:
The ARIC study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHS?N268201700004I). Neurocognitive data are collected by U01 2U01HL? 096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the National Institutes of Health (NIH) (NHLBI, National Institute of Neurological Disorders and Stroke [NINDS], National Institute on Aging [NIA], and National Institute on Deafness and Other Communication Disorders [NIDCD]), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. The ARIC-PET study is funded by the NIA (R01AG040282). Infrastructure was partly supported by grant number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This study was also supported by contracts K23 AG064122 (Dr Walker) and K24 AG052573 (Dr Gottesman) from the NIA. This research was supported in part by the Intramural Research Program of the NIH/NIA. Avid Radiopharmaceuticals provided the florbetapir isotope for the study but had no role in the study design or interpretation of results.
Funding Information:
Keenan A. Walker receives research funding from the NIH/NIA Intramural Research Program. Clifford R. Jack Jr serves on an independent data monitoring board for Roche, has served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from the NIH and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic. David S. Knopman served on a Data Safety Monitoring Board for the DIAN (Dominantly Inherited Alzheimer Network) study. He serves on a data safety monitoring board for a tau therapeutic for Biogen, but receives no personal compensation. He is a site investigator in the Biogen aducanumab trials. He is an investigator in a clinical trial sponsored by Lilly Pharmaceuticals and the University of Southern California. He serves as a consultant for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences but receives no personal compensation. He receives research support from the NIH. Dean F. Wong receives research funds as a contract through Washington University in St. Louis from LB Pharma, New York. Rebecca F. Gottesman is former Associate Editor for the journal Neurology. This article was prepared while Dr Rebecca Gottesman was employed at the Johns Hopkins University School of Medicine. The opinions expressed in this article are the author’s own and do not reflect the view of the NIH, the Department of Health and Human Services, or the US government.
Publisher Copyright:
© 2021 The Authors.
PY - 2021/9/7
Y1 - 2021/9/7
N2 - BACKGROUND: White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. METHODS AND RESULTS: Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion tensor imaging. Participants received florbetapir positron emission tomography imaging to measure brain amyloid. Associations between measures of white matter structure and elevated amyloid status were examined using multivariable logistic regression. Among 322 participants (43% Black), each SD increase in white matter hyperintensity volume was associated with a greater odds of elevated amyloid (odds ratio [OR], 1.37; 95% CI, 1.03–1.83) after adjusting for demo-graphic and cardiovascular risk factors. In race-stratified analyses, a greater white matter hyperintensity volume was more strongly associated with elevated amyloid among Black participants (OR, 2.00; 95% CI, 1.15–3.50), compared with White participants (OR, 1.29; 95% CI, 0.89–1.89). However, the race interaction was not statistically significant (P interaction=0.09). We found no association between white matter microstructure and elevated amyloid. CONCLUSIONS: The results suggest a modest positive relationship between white matter hyperintensity and elevated amyloid in older adults without dementia. Although the results indicate that this association is nonsignificantly stronger among Black participants, these findings will need to be confirmed or refuted using larger multiracial cohorts.
AB - BACKGROUND: White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. METHODS AND RESULTS: Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion tensor imaging. Participants received florbetapir positron emission tomography imaging to measure brain amyloid. Associations between measures of white matter structure and elevated amyloid status were examined using multivariable logistic regression. Among 322 participants (43% Black), each SD increase in white matter hyperintensity volume was associated with a greater odds of elevated amyloid (odds ratio [OR], 1.37; 95% CI, 1.03–1.83) after adjusting for demo-graphic and cardiovascular risk factors. In race-stratified analyses, a greater white matter hyperintensity volume was more strongly associated with elevated amyloid among Black participants (OR, 2.00; 95% CI, 1.15–3.50), compared with White participants (OR, 1.29; 95% CI, 0.89–1.89). However, the race interaction was not statistically significant (P interaction=0.09). We found no association between white matter microstructure and elevated amyloid. CONCLUSIONS: The results suggest a modest positive relationship between white matter hyperintensity and elevated amyloid in older adults without dementia. Although the results indicate that this association is nonsignificantly stronger among Black participants, these findings will need to be confirmed or refuted using larger multiracial cohorts.
KW - Alzheimer disease
KW - Amyloid
KW - Cerebral microbleeds
KW - Dementia
KW - White matter disease
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U2 - 10.1161/JAHA.121.022087
DO - 10.1161/JAHA.121.022087
M3 - Article
C2 - 34431373
AN - SCOPUS:85115241678
SN - 2047-9980
VL - 10
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 17
M1 - e022087
ER -