Abstract
Machine learning methods have been applied to estimate measures of brain aging from neuroimages. However, only rarely have these measures been examined in the context of biologic age. Here, we investigated associations of an MRI-based measure of dementia risk, the Alzheimer’s disease pattern similarity (AD-PS) scores, with measures used to calculate biological age. Participants were those from visit 5 of the Atherosclerosis Risk in Communities Study with cognitive status adjudication, proteomic data, and AD-PS scores available. The AD-PS score estimation is based on previously reported machine learning methods. We evaluated associations of the AD-PS score with all-cause mortality. Sensitivity analyses using only cognitively normal (CN) individuals were performed treating CNS-related causes of death as competing risk. AD-PS score was examined in association with 32 proteins measured, using a Somalogic platform, previously reported to be associated with age. Finally, associations with a deficit accumulation index (DAI) based on a count of 38 health conditions were investigated. All analyses were adjusted for age, race, sex, education, smoking, hypertension, and diabetes. The AD-PS score was significantly associated with all-cause mortality and with levels of 9 of the 32 proteins. Growth/differentiation factor 15 (GDF-15) and pleiotrophin remained significant after accounting for multiple-testing and when restricting the analysis to CN participants. A linear regression model showed a significant association between DAI and AD-PS scores overall. While the AD-PS scores were created as a measure of dementia risk, our analyses suggest that they could also be capturing brain aging.
| Original language | English |
|---|---|
| Pages (from-to) | 439-450 |
| Number of pages | 12 |
| Journal | GeroScience |
| Volume | 45 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2023 |
Bibliographical note
Publisher Copyright:© 2022, The Author(s), under exclusive licence to American Aging Association.
Funding
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Neurocognitive data is collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, and 2U01HL096917 from the NIH (NHLBI, NINDS, NIA, and NIDCD), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. The authors thank the staff and participants of the ARIC study for their important contributions. SomaLogic Inc. conducted the SomaScan assays in exchange for use of ARIC data. This work was supported in part by NIH/NHLBI grant R01 HL134320. RC and TH receive funding from the Wake Forest Alzheimer’s Disease Core Center (P30AG049638-01A1). We thank the ARIC Neurocognitive Study and the grant P30 AG021332 for funding to develop these analyses. RC and TH receive funding from the P30AG072947. Data collection and sharing for this project were also funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Neurocognitive data is collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, and 2U01HL096917 from the NIH (NHLBI, NINDS, NIA, and NIDCD), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. The authors thank the staff and participants of the ARIC study for their important contributions. SomaLogic Inc. conducted the SomaScan assays in exchange for use of ARIC data. This work was supported in part by NIH/NHLBI grant R01 HL134320. RC and TH receive funding from the Wake Forest Alzheimer’s Disease Core Center (P30AG049638-01A1). We thank the ARIC Neurocognitive Study and the grant P30 AG021332 for funding to develop these analyses. RC and TH receive funding from the P30AG072947. Data collection and sharing for this project were also funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
| Funders | Funder number |
|---|---|
| DOD ADNI | |
| Wake Forest Alzheimer’s Disease Core Center | P30 AG021332, P30AG049638-01A1, P30AG072947 |
| National Institutes of Health (NIH) | U01 AG024904 |
| National Institutes of Health (NIH) | |
| U.S. Department of Defense | W81XWH-12-2-0012 |
| U.S. Department of Defense | |
| National Institute on Aging | |
| National Heart, Lung, and Blood Institute (NHLBI) | 2U01HL096899, U01 2U01HL096812, 2U01HL096814, 2U01HL096902, HHSN268201700003I, 2U01HL096917 |
| National Heart, Lung, and Blood Institute (NHLBI) | |
| National Institute on Deafness and Other Communication Disorders | R01 HL134320, R01-HL70825 |
| National Institute on Deafness and Other Communication Disorders | |
| Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | |
| National Institute of Biomedical Imaging and Bioengineering | |
| University of Southern California | |
| DoD Alzheimer's Disease Neuroimaging Initiative | |
| Northern California Institute for Research and Education |
Keywords
- Aging
- Alzheimer’s disease
- Deficit accumulation index
- Machine learning
- Mortality
- Proteomics
ASJC Scopus subject areas
- Aging
- Veterinary (miscellaneous)
- Complementary and alternative medicine
- Geriatrics and Gerontology
- Cardiology and Cardiovascular Medicine
