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Regional rather than global brain age mediates cognitive function in cerebral small vessel disease

The factors and mechanisms underlying the heterogeneous cognitive outcomes of cerebral small vessel disease are largely unknown. Brain biological age can be estimated by machine learning algorithms that use large brain MRI data sets to integrate and compute neuroimaging-derived age-related features....

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Autores principales: Lee, Pei-Lin, Kuo, Chen-Yuan, Wang, Pei-Ning, Chen, Liang-Kung, Lin, Ching-Po, Chou, Kun-Hsien, Chung, Chih-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525017/
https://www.ncbi.nlm.nih.gov/pubmed/36196084
http://dx.doi.org/10.1093/braincomms/fcac233
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author Lee, Pei-Lin
Kuo, Chen-Yuan
Wang, Pei-Ning
Chen, Liang-Kung
Lin, Ching-Po
Chou, Kun-Hsien
Chung, Chih-Ping
author_facet Lee, Pei-Lin
Kuo, Chen-Yuan
Wang, Pei-Ning
Chen, Liang-Kung
Lin, Ching-Po
Chou, Kun-Hsien
Chung, Chih-Ping
author_sort Lee, Pei-Lin
collection PubMed
description The factors and mechanisms underlying the heterogeneous cognitive outcomes of cerebral small vessel disease are largely unknown. Brain biological age can be estimated by machine learning algorithms that use large brain MRI data sets to integrate and compute neuroimaging-derived age-related features. Predicted and chronological ages difference (brain-age gap) reflects advanced or delayed brain aging in an individual. The present study firstly reports the brain aging status of cerebral small vessel disease. In addition, we investigated whether global or certain regional brain age could mediate the cognitive functions in cerebral small vessel disease. Global and regional (400 cortical, 14 subcortical and 28 cerebellum regions of interest) brain-age prediction models were constructed using grey matter features from MRI of 1482 healthy individuals (age: 18–92 years). Predicted and chronological ages differences were obtained and then applied to non-stroke, non-demented individuals, aged ≥50 years, from another community-dwelling population (I-Lan Longitudinal Aging Study cohort). Among the 734 participants from the I-Lan Longitudinal Aging Study cohort, 124 were classified into the cerebral small vessel disease group. The cerebral small vessel disease group demonstrated significantly poorer performances in global cognitive, verbal memory and executive functions than that of non-cerebral small vessel disease group. Global brain-age gap was significantly higher in the cerebral small vessel disease (3.71 ± 7.60 years) than that in non-cerebral small vessel disease (−0.43 ± 9.47 years) group (P = 0.003, η(2) = 0.012). There were 82 cerebral cortical, 3 subcortical and 4 cerebellar regions showing significantly different brain-age gap between the cerebral small vessel disease and non-cerebral small vessel disease groups. Global brain-age gap failed to mediate the relationship between cerebral small vessel disease and any of the cognitive domains. In 89 regions with increased brain-age gap in the cerebral small vessel disease group, seven regional brain-age gaps were able to show significant mediation effects in cerebral small vessel disease-related cognitive impairment (we set the statistical significance P < 0.05 uncorrected in 89 mediation models). Of these, the left thalamus and left hippocampus brain-age gap explained poorer global cognitive performance in cerebral small vessel disease. We demonstrated the interconnections between cerebral small vessel disease and brain age. Strategic brain aging, i.e. advanced brain aging in critical regions, may be involved in the pathophysiology of cerebral small vessel disease-related cognitive impairment. Regional rather than global brain-age gap could potentially serve as a biomarker for predicting heterogeneous cognitive outcomes in patients with cerebral small vessel disease.
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spelling pubmed-95250172022-10-03 Regional rather than global brain age mediates cognitive function in cerebral small vessel disease Lee, Pei-Lin Kuo, Chen-Yuan Wang, Pei-Ning Chen, Liang-Kung Lin, Ching-Po Chou, Kun-Hsien Chung, Chih-Ping Brain Commun Original Article The factors and mechanisms underlying the heterogeneous cognitive outcomes of cerebral small vessel disease are largely unknown. Brain biological age can be estimated by machine learning algorithms that use large brain MRI data sets to integrate and compute neuroimaging-derived age-related features. Predicted and chronological ages difference (brain-age gap) reflects advanced or delayed brain aging in an individual. The present study firstly reports the brain aging status of cerebral small vessel disease. In addition, we investigated whether global or certain regional brain age could mediate the cognitive functions in cerebral small vessel disease. Global and regional (400 cortical, 14 subcortical and 28 cerebellum regions of interest) brain-age prediction models were constructed using grey matter features from MRI of 1482 healthy individuals (age: 18–92 years). Predicted and chronological ages differences were obtained and then applied to non-stroke, non-demented individuals, aged ≥50 years, from another community-dwelling population (I-Lan Longitudinal Aging Study cohort). Among the 734 participants from the I-Lan Longitudinal Aging Study cohort, 124 were classified into the cerebral small vessel disease group. The cerebral small vessel disease group demonstrated significantly poorer performances in global cognitive, verbal memory and executive functions than that of non-cerebral small vessel disease group. Global brain-age gap was significantly higher in the cerebral small vessel disease (3.71 ± 7.60 years) than that in non-cerebral small vessel disease (−0.43 ± 9.47 years) group (P = 0.003, η(2) = 0.012). There were 82 cerebral cortical, 3 subcortical and 4 cerebellar regions showing significantly different brain-age gap between the cerebral small vessel disease and non-cerebral small vessel disease groups. Global brain-age gap failed to mediate the relationship between cerebral small vessel disease and any of the cognitive domains. In 89 regions with increased brain-age gap in the cerebral small vessel disease group, seven regional brain-age gaps were able to show significant mediation effects in cerebral small vessel disease-related cognitive impairment (we set the statistical significance P < 0.05 uncorrected in 89 mediation models). Of these, the left thalamus and left hippocampus brain-age gap explained poorer global cognitive performance in cerebral small vessel disease. We demonstrated the interconnections between cerebral small vessel disease and brain age. Strategic brain aging, i.e. advanced brain aging in critical regions, may be involved in the pathophysiology of cerebral small vessel disease-related cognitive impairment. Regional rather than global brain-age gap could potentially serve as a biomarker for predicting heterogeneous cognitive outcomes in patients with cerebral small vessel disease. Oxford University Press 2022-09-14 /pmc/articles/PMC9525017/ /pubmed/36196084 http://dx.doi.org/10.1093/braincomms/fcac233 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Pei-Lin
Kuo, Chen-Yuan
Wang, Pei-Ning
Chen, Liang-Kung
Lin, Ching-Po
Chou, Kun-Hsien
Chung, Chih-Ping
Regional rather than global brain age mediates cognitive function in cerebral small vessel disease
title Regional rather than global brain age mediates cognitive function in cerebral small vessel disease
title_full Regional rather than global brain age mediates cognitive function in cerebral small vessel disease
title_fullStr Regional rather than global brain age mediates cognitive function in cerebral small vessel disease
title_full_unstemmed Regional rather than global brain age mediates cognitive function in cerebral small vessel disease
title_short Regional rather than global brain age mediates cognitive function in cerebral small vessel disease
title_sort regional rather than global brain age mediates cognitive function in cerebral small vessel disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525017/
https://www.ncbi.nlm.nih.gov/pubmed/36196084
http://dx.doi.org/10.1093/braincomms/fcac233
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