title: Reduced cerebellar gray matter is a neural signature of physical frailty.
abstract: Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I-Lan Longitudinal Aging Study randomly sampled community-dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail (n = 178, 39.0%) and frail (n = 19, 4.2%) subjects were grouped for analysis. The prefrail-frail group showed reduced GMV, compared to the robust group (n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor-related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum- and noncerebellum-based frailty components reflect a distinctive future risk for developing frailty.
authors.affiliation: Department of Neurology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Brain Science, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Ta
authors.initials: WT
authors.lastname: Chen
authors.affiliation: Brain Research Center, National Yang-Ming University, Taipei, Taiwan.|Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kun-Hsien
authors.initials: KH
authors.lastname: Chou
authors.affiliation: Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan.|Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Li-Kuo
authors.initials: LK
authors.lastname: Liu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Lee
authors.affiliation: Department of Family Medicine, Taipei Veterans General Hospital Yuanshan Branch, Yi-Lan, Taiwan.
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan.|Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Liang-Kung
authors.initials: LK
authors.lastname: Chen
authors.affiliation: Department of Neurology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan.|Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan.
authors.forename: Pei-Ning
authors.initials: PN
authors.lastname: Wang
authors.affiliation: Brain Research Center, National Yang-Ming University, Taipei, Taiwan.|Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lin
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology / Q000502:physiology; D002531:Cerebellum / Q000473:pathology*; D016000:Cluster Analysis; D005260:Female; D016330:Frail Elderly; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009929:Organ Size; D012720:Severity of Illness Index; D013624:Taiwan / Q000453:epidemiology
keywords: magnetic resonance imaging; muscle weakness; physical activity; physical frailty; voxel-based morphometry; walking speed