Abstract
Background: Frailty and cognitive impairment are closely related in sharing several possible underlying pathophysiological mechanisms. There is a lack of clarity in published literature on whether cerebral infarcts or Alzheimer’s pathology accounts for the frailty phenotype in patients with mild Alzheimer’s disease (AD). Therefore, we investigated the structural neuroimaging predictors of frailty in mild AD patients to better elucidate the underlying pathophysiology. Methods: We recruited subjects who satisfied inclusion criteria from a clinical database of patients attending a tertiary hospital memory clinic between 2012 and 2017. AD patients with Clinical Dementia Rating (CDR) 0.5 and 1.0 who had undergone MRI brain were included. Frailty Index (FI-CGA) was utilised for frailty assessment, and visual MRI rating scales were used by blinded raters to quantify the brain lesions. Results: A total of 342 mild AD patients with a mean age of 75.79 ± 7.18 were studied. A multivariate linear regression model adjusted for demographics, cognitive scores and functional status revealed only deep white matter hyperintensities (DWMH) but none other brain lesions to be significantly and positively correlated with FI-CGA (β = 0.178, SE = 0.047, p ≤ 0.001) This model which comprised age, CDR sum of boxes, basic activities of living and DWMH, accounted for 47.5% of the FI-CGA variance in the study population. Conclusions: The study has revealed DWMH to be independently associated with frailty in mild AD patients. With the current understanding of the aetiology of DWMH, control of vascular risk factors is vital to preventing and ameliorating frailty in patients with mild AD.
Highlights
Frailty is a state of increased vulnerability due to decreased physiologic reserves and dysregulation of multiple physiologic systems [1]
We found that frailty index (FI)-comprehensive geriatric assessment (CGA) correlated positively with age and Clinical Dementia Rating (CDR) Sum of Boxes (SOB), and negatively with Mini-Mental State Exam (MMSE) and functional scores
Our study has revealed an independent relationship between deep white matter hyperintensities (DWMH) and frailty in mild Alzheimer’s disease (AD)
Summary
Frailty is a state of increased vulnerability due to decreased physiologic reserves and dysregulation of multiple physiologic systems [1]. Other studies have reported an association between physical frailty and cognitive impairment [4,5,6] and the mechanisms proposed include vascular disease, subcellular disturbances, systemic disorders, chronic inflammation, and impaired mitochondrial function [6,7]. Alzheimer pathology but not cerebral infarcts have been reported to be associated with increased levels of frailty. As those studies were done through autopsied participants using the subcomponents of frailty as outcomes, there are limitations in generalising the results for clinical purposes [12,13,14]. We investigated the structural neuroimaging predictors of frailty in mild AD patients to better elucidate the underlying pathophysiology
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