Mathilde Antoniades, Dhivya Srinivasan, Junhao Wen, Guray Erus, Ahmed Abdulkadir, Elizabeth Mamourian, Randa Melhem, Gyujoon Hwang, Yuhan Cui, Sindhuja Tirumalai Govindarajan, Andrew A Chen, Zhen Zhou, Zhijian Yang, Jiong Chen, Raymond Pomponio, Susan Sotardi, Yang An, Murat Bilgel, Pamela LaMontagne, Ashish Singh, Tammie Benzinger, Lori Beason-Held, Daniel S Marcus, Kristine Yaffe, Lenore Launer, John C Morris, Duygu Tosun, Luigi Ferrucci, R Nick Bryan, Susan M Resnick, Mohamad Habes, David Wolk, Yong Fan, Ilya M Nasrallah, Haochang Shou, Christos Davatzikos
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These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).</p><p><strong>Methods: </strong>Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age range spanning 42-85 years. Participants were categorised into four groups based on the difference between their chronological and predicted age in each modality: advanced age in both (n = 291), resilient in both (n = 260) or advanced in one/resilient in the other (n = 163/153). With the resilient group as the reference, brain-age groups were compared across neuroimaging features of neuropathology (white matter hyperintensity volume, neuronal loss measured with Neurite Orientation Dispersion and Density Imaging, AD-specific atrophy patterns measured with the Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease index, amyloid burden using amyloid positron emission tomography (PET), progression to mild cognitive impairment and baseline and longitudinal cognitive measures (trail making task, mini mental state examination, digit symbol substitution task).</p><p><strong>Findings: </strong>Individuals with advanced structural and functional brain-ages had more features indicative of neurodegeneration and they had poor cognition. Individuals with a resilient brain-age in both modalities had a genetic variant that has been shown to be associated with age of onset of AD. Mixed brain-age was associated with selective cognitive deficits.</p><p><strong>Interpretation: </strong>The advanced group displayed evidence of increased atrophy across all neuroimaging features that was not found in either of the mixed groups. This is in line with biomarkers of preclinical AD and cerebrovascular disease. These findings suggest that the variation in structural and functional brain ageing across individuals reflects the degree of underlying neuropathological processes and may indicate the propensity to develop dementia in later life.</p><p><strong>Funding: </strong>The National Institute on Aging, the National Institutes of Health, the Swiss National Science Foundation, the Kaiser Foundation Research Institute and the National Heart, Lung, and Blood Institute.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536027/pdf/","citationCount":"0","resultStr":"{\"title\":\"Relationship between MRI brain-age heterogeneity, cognition, genetics and Alzheimer's disease neuropathology.\",\"authors\":\"Mathilde Antoniades, Dhivya Srinivasan, Junhao Wen, Guray Erus, Ahmed Abdulkadir, Elizabeth Mamourian, Randa Melhem, Gyujoon Hwang, Yuhan Cui, Sindhuja Tirumalai Govindarajan, Andrew A Chen, Zhen Zhou, Zhijian Yang, Jiong Chen, Raymond Pomponio, Susan Sotardi, Yang An, Murat Bilgel, Pamela LaMontagne, Ashish Singh, Tammie Benzinger, Lori Beason-Held, Daniel S Marcus, Kristine Yaffe, Lenore Launer, John C Morris, Duygu Tosun, Luigi Ferrucci, R Nick Bryan, Susan M Resnick, Mohamad Habes, David Wolk, Yong Fan, Ilya M Nasrallah, Haochang Shou, Christos Davatzikos\",\"doi\":\"10.1016/j.ebiom.2024.105399\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. 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Relationship between MRI brain-age heterogeneity, cognition, genetics and Alzheimer's disease neuropathology.
Background: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).
Methods: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age range spanning 42-85 years. Participants were categorised into four groups based on the difference between their chronological and predicted age in each modality: advanced age in both (n = 291), resilient in both (n = 260) or advanced in one/resilient in the other (n = 163/153). With the resilient group as the reference, brain-age groups were compared across neuroimaging features of neuropathology (white matter hyperintensity volume, neuronal loss measured with Neurite Orientation Dispersion and Density Imaging, AD-specific atrophy patterns measured with the Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease index, amyloid burden using amyloid positron emission tomography (PET), progression to mild cognitive impairment and baseline and longitudinal cognitive measures (trail making task, mini mental state examination, digit symbol substitution task).
Findings: Individuals with advanced structural and functional brain-ages had more features indicative of neurodegeneration and they had poor cognition. Individuals with a resilient brain-age in both modalities had a genetic variant that has been shown to be associated with age of onset of AD. Mixed brain-age was associated with selective cognitive deficits.
Interpretation: The advanced group displayed evidence of increased atrophy across all neuroimaging features that was not found in either of the mixed groups. This is in line with biomarkers of preclinical AD and cerebrovascular disease. These findings suggest that the variation in structural and functional brain ageing across individuals reflects the degree of underlying neuropathological processes and may indicate the propensity to develop dementia in later life.
Funding: The National Institute on Aging, the National Institutes of Health, the Swiss National Science Foundation, the Kaiser Foundation Research Institute and the National Heart, Lung, and Blood Institute.
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍:
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.