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.

Skeletal muscle performance and ageing

“…In vivo , imaging‐based studies have corroborated these findings, suggesting that cortical thinning occurs by middle age and that areas near the primary motor cortex demonstrate prominent atrophy . Reduced cerebellar grey matter has been linked to weakness, low activity, and slowness . Additionally, age‐related differences also exist in white matter mass and length of myelinated nerve fibres .…”

“…Cross‐sectional evidence from 74 healthy men and women aged 18–90 years indicates that age is inversely related with vastus lateralis mitochondrial DNA (−0.62, P < 0.001) and with mRNA transcription ( r = −0.48/−0.54, P < 0.001) . This decline may result in lower mitochondrial muscle protein synthesis rates in older adults . Not only the mitochondrial content is important for elderly skeletal muscle performance, the mitochondrial function (i.e.…”

Neuroimaging signatures of frailty: A population‐based study in community‐dwelling older adults (the Atahualpa Project)

“…Despite considerable literature on frailty, just three studies have investigated the occurrence of structural brain lesions in frail persons . In two of them, the diagnosis was based on the frailty phenotype described by Fried, and the cognitive component of frailty was not investigated .…”

Precision geriatrics: Comprehensiveness and individualization for frailty intervention

“…19 Moreover, mobility subtype frailty is associated with cognitive declines in non-memory domains, mainly executive function. 20,21 Brain imaging of the same cohort revealed significantly reduced cerebellar gray matter among pre-frail and frail older adults, 22 especially those with mobility subtype frailty. Diminished executive function and gray matter in mobility subtype frailty suggest that a specific neurodegenerative process related to the cerebellum may affect some people with physical frailty.…”