The Influence of Co-Morbidity and Frailty on the Clinical Manifestation of Patients with Alzheimer's Disease

Co-morbidity and frailty are common in Alzheimer's disease (AD) and may contribute to the heterogeneity in clinical manifestations of the disease. We cross-sectionally investigated whether co-morbidity and frailty were independently associated with the clinical manifestation of AD in the 4C-Dementia study; a multicenter, longitudinal study in newly diagnosed AD patients. Clinical manifestation was operationalized using a composite of cognitive performance (neuropsychological assessment), activities of daily living (Disability Assessment for Dementia; DAD) and neuropsychiatric symptoms (Neuropsychiatric Inventory). As predictors of prime interest, co-morbidity was determined using the Cumulative Illness Rating Scale (CIRS-G) and frailty by the Fried criteria. In total, 213 AD patients participated (mean age 75 +/- 10 years; 58% females). In linear regression models adjusted for age, gender, education, and disease duration, CIRS-G (beta= -0.21, p < 0.01) and frailty (beta = -0.34, p < 0.001) were separately associated with clinical AD manifestation. However, CIRS-G (beta = -0.12, p = 0.12) lost statistical significance when both were combined (frailty: beta = -0.31, p < 0.001). Models with the individual components of clinical AD manifestation as dependent variables show significant associations between cognitive performance and CIRS-G (beta = -0.22, p = 0.01), and between DAD and frailty (beta = -0.37, p < 0.001). Our findings indicate that physical health and clinical AD manifestation are associated. This association may be responsible for part of the heterogeneity in the presentation of AD. This emphasizes the importance of adequate assessment of co-morbid medical conditions and frailty in patients with AD.