Microstructural Brain Changes Associated With Frailty in Older Adults: Insights From Diffusion Tensor Imaging

This study investigates the relationship between frailty status and white matter integrity (WMI) in older adults, focusing on associations with frailty status.

A cross-sectional study.

125 older adults aged ≥65 years without dementia were included.

A comprehensive geriatric assessment was conducted. Frailty status was evaluated by Fried Frailty criteria: unintentional weight loss, exhaustion, low levels of activity, weakness, and slowness: 0 for nonfrail, 1 to 2 for prefrail, and 3 to 5 for frail. Brain magnetic resonance imaging with diffusion tensor imaging (DTI) was performed, and mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity values were calculated in white matter integrity using a region of interest-based method. Multinomial logistic regression analyzed the multivariate effects of clinical variables on the frailty-WMI association, whereas canonical correlation analysis examined multivariate relationships between diffusion tensor imaging measurements and geriatric assessment parameters.

The mean age was 81.76 ± 7.07 years, and 64% were female. Of the participants, 55.2% were frail, 33.6% prefrail, and 11.2% nonfrail. After adjusting for age and sex, WMI impairment varied in the cingulum, inferior longitudinal fasciculus, and forceps major in the left hemisphere among frailty statuses. Regression analysis showed demyelination of the left cingulum [odds ratio (OR) 0.97, 95% CI 0.95-0.99] and left forceps major (OR 0.99, 95% CI 0.98-0.99) was linked to increased frailty risk. For the frail group, DTI variables and malnutrition were significant. An increase in malnutrition status or risk raised the risk of frailty by 18.86 times. Canonical correlation analysis identified the Lawton-Brody IADL and Epworth Sleepiness Scale scores as the strongest predictors, whereas the cingulum showed the highest association among white matter tracts.

Frailty and prefrailty were associated with deteriorated WMI, particularly in the left cingulum and left forceps major. The strong link between frailty and WMI may reflect shared underlying mechanisms, including sleep, functionality, and nutrition. Therefore, a multidimensional approach to frailty is important.