Machine learning reveals distinct neuroanatomical signatures of cardiovascular and metabolic diseases in cognitively unimpaired individuals

Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the d...

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Veröffentlicht in:Nature communications Jg. 16; H. 1; S. 2724 - 12
Hauptverfasser: Govindarajan, Sindhuja Tirumalai, Mamourian, Elizabeth, Erus, Guray, Abdulkadir, Ahmed, Melhem, Randa, Doshi, Jimit, Pomponio, Raymond, Tosun, Duygu, Bilgel, Murat, An, Yang, Sotiras, Aristeidis, Marcus, Daniel S., LaMontagne, Pamela, Benzinger, Tammie L. S., Espeland, Mark A., Masters, Colin L., Maruff, Paul, Launer, Lenore J., Fripp, Jurgen, Johnson, Sterling C., Morris, John C., Albert, Marilyn S., Bryan, R. Nick, Resnick, Susan M., Habes, Mohamad, Shou, Haochang, Wolk, David A., Nasrallah, Ilya M., Davatzikos, Christos
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 19.03.2025
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ISSN:2041-1723, 2041-1723
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Abstract Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45–85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45–64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies. Cardiovascular and metabolic risk factors (CVM) impact brain structure and increase dementia risk. Here, the authors developed and validated machine learning models to measure the neuroanatomical changes in people with cardiovascular and metabolic diseases that are cognitively unimpaired.
AbstractList Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45–85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45–64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies. Cardiovascular and metabolic risk factors (CVM) impact brain structure and increase dementia risk. Here, the authors developed and validated machine learning models to measure the neuroanatomical changes in people with cardiovascular and metabolic diseases that are cognitively unimpaired.
Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45–85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45–64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies.Cardiovascular and metabolic risk factors (CVM) impact brain structure and increase dementia risk. Here, the authors developed and validated machine learning models to measure the neuroanatomical changes in people with cardiovascular and metabolic diseases that are cognitively unimpaired.
Abstract Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45–85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45–64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies.
Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45–85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45–64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies.
Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45-85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45-64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies.Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45-85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45-64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies.
ArticleNumber 2724
Author Wolk, David A.
Abdulkadir, Ahmed
LaMontagne, Pamela
Bilgel, Murat
Fripp, Jurgen
Erus, Guray
Maruff, Paul
Nasrallah, Ilya M.
Resnick, Susan M.
Albert, Marilyn S.
Shou, Haochang
Pomponio, Raymond
Bryan, R. Nick
Melhem, Randa
Sotiras, Aristeidis
Govindarajan, Sindhuja Tirumalai
Masters, Colin L.
Mamourian, Elizabeth
Doshi, Jimit
Tosun, Duygu
Benzinger, Tammie L. S.
Launer, Lenore J.
Davatzikos, Christos
Habes, Mohamad
Johnson, Sterling C.
Morris, John C.
Marcus, Daniel S.
An, Yang
Espeland, Mark A.
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/40108173$$D View this record in MEDLINE/PubMed
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GrantInformation_xml – fundername: The iSTAGING study is a multi-institutional effort funded by the National Institute on Aging (NIA) by RF1 AG054409 (C. Davatzikos). Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. ADNI is funded by the NIA, 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; Biogen; Bristol-Myers Squibb; CereSpir; Cogstate; Eisai; Elan Pharmaceuticals; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche and its affiliated company Genentech; Fujirebio; GE Healthcare; IXICO; Janssen Alzheimer Immunotherapy Research & Development; Johnson & Johnson Pharmaceutical Research & Development; Lumosity; Lundbeck; Merck & Co; Meso Scale Diagnostics; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer; 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. Data used in the preparation of this article was obtained from the Australian Imaging Biomarkers and Lifestyle flagship study of ageing (AIBL) funded by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) which was made available at the ADNI database (www.loni.usc.edu/ADNI). The AIBL researchers contributed data but did not participate in analysis or writing of this report. AIBL researchers are listed at www.aibl.csiro.au. The BIOCARD study is partly supported by NIH grant U19-AG033655 (M.S. Albert). The BLSA neuroimaging study is funded by the Intramural Research Program, NIA, National Institutes of Health (NIH), and by HHSN271201600059C (S. M. Resnick, M. Bilgel, Y. An). CARDIA study is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005) (L.J. Launer). Data used in the preparation of this article was obtained from the OASIS study funded in part by grants P50 AG05681, P01 AG03991, P01 AG026276, R01 AG021910, P20 MH071616, U24 RR021382 for OASIS-1, P50 AG05681, P01 AG03991, P01 AG026276, R01 AG021910, P20 MH071616, U24 RR021382 for OASIS-2, and NIH P30 AG066444, P50 AG00561, P30 NS09857781, P01 AG026276, P01 AG003991, R01 AG043434, UL1 TR000448, R01 EB009352 for OASIS-3 (T. Benzinger, D. Marcus, J. Morris, P. LaMontagne). Data used in the preparation of this article was obtained at Penn Alzheimer’s Disease Research Center funded in part by grant P30 AG072979 (D.A. Wolk). Data used in the preparation of this article was obtained from the UK Biobank Resource under application number 35148. The Women’s Health Initiative was funded by the National Heart, Lung and Blood Institute of the NIH, US Department of Health and Human Services. Contracts HHSN268200464221C and N01-WH-4-4221 provided additional support. The WHIMS (M.A. Espeland) was funded in part by Wyeth Pharmaceuticals. The WRAP study was supported by grants: NIH R01AG027161 and R01AG054047 (S.C. Johnson). The authors would like to acknowledge the clinical and neuropathology diagnostic support provided by the Wisconsin ADRC’s Clinical, Neuropathology and Biomarkers Cores, and biostatistical support provided by the Data Management and Biostatistics Core. S.T. Govindarajan was partly supported by the Alzheimer’s Association Research Fellowship AARFD-23-1151286. A. Abdulkadir was funded through grants 191026 and 206795 awarded by the Swiss National Science Foundation. M. Habes was supported by grant 1R01AG080821 from the National Institutes of Health.
– fundername: U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
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Snippet Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic...
Abstract Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic...
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Title Machine learning reveals distinct neuroanatomical signatures of cardiovascular and metabolic diseases in cognitively unimpaired individuals
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