Deep but Not Periventricular White Matter Disease Is a Marker for Frailty in Older Patients with Early Alzheimer’s Disease

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.