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


Siejka, TP and Srikanth, VK and Hubbard, RE and Moran, C and Beare, R and Wood, AG and Collyer, TA and Gujjari, S and Phan, TG and Callisaya, ML, Frailty is associated with cognitive decline independent of cerebral small vessel disease and brain atrophy, Journals of Gerontology: Series A, 77, (9) pp. 1819-1826. ISSN 1079-5006 (2022) [Refereed Article]

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Copyright Statement

Copyright the authors 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: doi:10.1093/gerona/glac078



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.


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 6085 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.


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).


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.

Item Details

Item Type:Refereed Article
Keywords:Brain atrophy, cerebral small vessel disease, cognitive decline, frailty, cognition, brain, dementia
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Geriatrics and gerontology
Objective Division:Health
Objective Group:Provision of health and support services
Objective Field:Primary care
UTAS Author:Srikanth, VK (Dr Velandai Srikanth)
UTAS Author:Callisaya, ML (Dr Michele Callisaya)
ID Code:150250
Year Published:2022
Funding Support:National Health and Medical Research Council (1135761)
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-06-05
Last Modified:2022-11-29
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