TY - JOUR
T1 - Associations of Vascular Risk and Amyloid Burden with Subsequent Dementia
AU - Gottesman, Rebecca F.
AU - Wu, Aozhou
AU - Coresh, Josef
AU - Knopman, David S.
AU - Jack, Clifford R.
AU - Rahmim, Arman
AU - Sharrett, A. Richey
AU - Spira, Adam P.
AU - Wong, Dean F.
AU - Wagenknecht, Lynne E.
AU - Hughes, Timothy M.
AU - Walker, Keenan A.
AU - Mosley, Thomas H.
N1 - Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by NIH National Heart, Lung, and Blood Institute contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I). Neurocognitive data were collected with support by grants U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the NIH (National Heart, Lung, and Blood Institute, with support from the National Institute of Neurological Disorders and Stroke [NINDS], National Institute on Aging [NIA], and National Institute on Deafness and Other Communication Disorders), and with previous brain MRI examinations funded by R01‐HL70825 from the National Heart, Lung, and Blood Institute. The ARIC‐PET study is funded by the National Institute on Aging (R01AG040282). Avid Radiopharmaceuticals provided the florbetapir isotope for the study, but had no role in the study design or interpretation of results. Support was also provided during part of the study by K24 AG052573 (R.F.G.) as well as the NINDS Intramural Research Program (R.F.G.). This research was also supported by the NIA Intramural Research Program (K.A.W.).
Funding Information:
R.F.G. was a previous Associate Editor for the journal . A.W. has received consulting fees from Analysis Group, which are not relevant to the presenting study. C.R.J. serves on an independent data monitoring board for Roche, has served as a speaker for Eisai, and has consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from the NIH, the GHR Foundation, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. D.S.K. serves on a data safety monitoring board for the Dominantly Inherited Alzheimer Network Treatment Unity study. He served on a data safety monitoring board for a tau therapeutic for Biogen but received no personal compensation. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. He has served as a consultant for Roche, Samus Therapeutics, Magellan Health, and Alzeca Biosciences but receives no personal compensation. He receives funding from the NIH. A.P.S. has received payment as a consultant for Merck and has received honoraria from Springer Nature Switzerland for guest editing special issues of . The other authors have no disclosures. Neurology Current Sleep Medicine Reports
Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by NIH National Heart, Lung, and Blood Institute contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I). Neurocognitive data were collected with support by grants U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the NIH (National Heart, Lung, and Blood Institute, with support from the National Institute of Neurological Disorders and Stroke [NINDS], National Institute on Aging [NIA], and National Institute on Deafness and Other Communication Disorders), and with previous brain MRI examinations funded by R01-HL70825 from the National Heart, Lung, and Blood Institute. The ARIC-PET study is funded by the National Institute on Aging (R01AG040282). Avid Radiopharmaceuticals provided the florbetapir isotope for the study, but had no role in the study design or interpretation of results. Support was also provided during part of the study by K24 AG052573 (R.F.G.) as well as the NINDS Intramural Research Program (R.F.G.). This research was also supported by the NIA Intramural Research Program (K.A.W.). The authors thank the staff and participants of the ARIC study.
Publisher Copyright:
© 2022 American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
PY - 2022/10
Y1 - 2022/10
N2 - Objective: Midlife vascular risk factors (MVRFs) are associated with incident dementia, as are amyloid β (Aβ) deposition and neurodegeneration. Whether vascular and Alzheimer disease-associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood. Methods: Participants in the Atherosclerosis Risk in Communities–Positron Emission Tomography study were followed from 1987–1989 (45–64 years old) through 2016–2017 (74–94 years old), with repeat cognitive assessment and dementia adjudication. In 2011–2013, dementia-free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (Aβ) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated Aβ standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models. Results: In 298 individuals, 36 developed dementia (median follow-up = 4.9 years). Midlife hypertension and Aβ each independently predicted dementia risk (hypertension: hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.16–5.67; Aβ SUVR [per standard deviation (SD)]: HR = 2.57, 95% CI = 1.72–3.84), but did not interact significantly, whereas late life diabetes (HR = 2.50, 95% CI = 1.18–5.28) and Aβ independently predicted dementia risk. WMHs (per SD: HR = 1.51, 95% CI = 1.03–2.20) and Aβ SUVR (HR = 2.52, 95% CI = 1.83–3.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of Aβ and MVRFs (HR = 2.18, 95% CI = 1.18–4.01). Interpretation: Midlife hypertension and late life Aβ are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607–619.
AB - Objective: Midlife vascular risk factors (MVRFs) are associated with incident dementia, as are amyloid β (Aβ) deposition and neurodegeneration. Whether vascular and Alzheimer disease-associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood. Methods: Participants in the Atherosclerosis Risk in Communities–Positron Emission Tomography study were followed from 1987–1989 (45–64 years old) through 2016–2017 (74–94 years old), with repeat cognitive assessment and dementia adjudication. In 2011–2013, dementia-free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (Aβ) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated Aβ standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models. Results: In 298 individuals, 36 developed dementia (median follow-up = 4.9 years). Midlife hypertension and Aβ each independently predicted dementia risk (hypertension: hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.16–5.67; Aβ SUVR [per standard deviation (SD)]: HR = 2.57, 95% CI = 1.72–3.84), but did not interact significantly, whereas late life diabetes (HR = 2.50, 95% CI = 1.18–5.28) and Aβ independently predicted dementia risk. WMHs (per SD: HR = 1.51, 95% CI = 1.03–2.20) and Aβ SUVR (HR = 2.52, 95% CI = 1.83–3.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of Aβ and MVRFs (HR = 2.18, 95% CI = 1.18–4.01). Interpretation: Midlife hypertension and late life Aβ are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607–619.
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U2 - 10.1002/ana.26447
DO - 10.1002/ana.26447
M3 - Article
C2 - 35732594
AN - SCOPUS:85135209005
SN - 0364-5134
VL - 92
SP - 607
EP - 619
JO - Annals of neurology
JF - Annals of neurology
IS - 4
ER -