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

Abstract

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 (β = -0.21, p < 0.01) and frailty (β = -0.34, p < 0.001) were separately associated with clinical AD manifestation. However, CIRS-G (β = -0.12, p = 0.12) lost statistical significance when both were combined (frailty: β = -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 (β = -0.22, p = 0.01), and between DAD and frailty (β = -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.

Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

“…Studies of imaging and pathology in AD show faster evolving brain atrophy in early-onset than in late-onset AD [28], which is in contrast to our study where some of the younger patients with mild or very mild AD showed little progression. The heterogeneity of our sample regarding age and disease severity indicates that age-related comorbidities may be of importance for disease progression although this could not be shown by the analyses in the present study [29].…”

Comorbidity and progression of late onset Alzheimer’s disease: A systematic review

“…Adjustment for baseline age was unclear in two studies [15, 19]. Adjustment for education was lacking or unclear in five studies examining cognition [16, 17, 19–21]. Adjustment for baseline symptoms of interest was unclear in one out of six longitudinal studies [19].…”

“…An overview of these studies, including their measurement scales and results is provided in Table 2. Eight studies used the Mini-Mental State Examination (MMSE) [27] to measure cognition, one used the Global Deterioration Scale (GDS) [28] and one used a composite score of neuropsychological tests [16]. The presence of comorbidities was related to decreased cognitive abilities in seven out of the ten studies examining cognition.…”

A profile of The Clinical Course of Cognition and Comorbidity in Mild Cognitive Impairment and Dementia Study (The 4C study): two complementary longitudinal, clinical cohorts in the Netherlands

“…The total CIRS-G score leaving out the category of psychiatric illness was higher in the dementia than in the MCI cohort. For the AD patients in the dementia cohort, it was found that comorbidities were associated with cognitive performance; frailty was associated with functional abilities at baseline [25]. Comparing older and younger persons with dementia contrasting persons from the 4c Dementia cohort data with persons from the NeedYD cohort [26], showed that younger persons had less comorbidity and may more often have neurological comorbidities than older persons with dementia [27].…”