Frailty is associated with cognitive decline independent of cerebral small vessel disease and brain atrophy

Timothy P Siejka, Velandai K Srikanth, Ruth E Hubbard, Chris Moran, Richard Beare, Amanda G Wood, Taya A Collyer, Siddhanth Gujjari, Thanh G Phan, Michele L Callisaya

Research output: Contribution to journalArticlepeer-review


BACKGROUND: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status.

METHODS: The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60-85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education.

RESULTS: A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time β -0.001, 95% confidence interval [CI] -0.003, -0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03).

CONCLUSION: These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline.

Original languageEnglish
Pages (from-to)1819-1826
JournalJournals of Gerontology: Series A
Issue number9
Early online date1 Apr 2022
Publication statusPublished - 1 Sept 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact


  • Brain atrophy
  • Cerebral small vessel disease
  • Cognitive decline
  • Frailty


Dive into the research topics of 'Frailty is associated with cognitive decline independent of cerebral small vessel disease and brain atrophy'. Together they form a unique fingerprint.

Cite this