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

Abstract

BackgroundAlzheimer’s disease is a neurodegenerative syndrome characterized by multiple dimensions including cognitive decline, decreased daily functioning and psychiatric symptoms. This systematic review aims to investigate the relation between somatic comorbidity burden and progression in late-onset Alzheimer’s disease (LOAD).MethodsWe searched four databases for observational studies that examined cross-sectional or longitudinal associations of cognitive or functional or neuropsychiatric outcomes with comorbidity in individuals with LOAD. From the 7966 articles identified originally, 11 studies were included in this review. The Newcastle-Ottawa quality assessment was used. The large variation in progression measures, comorbidity indexes and study designs hampered the ability to perform a meta-analysis. This review was registered with PROSPERO under DIO: 10.15124/CRD42015027046.ResultsNine studies indicated that comorbidity burden was associated with deterioration in at least one of the three dimensions of LOAD examined. Seven out of ten studies investigating cognition found comorbidities to be related to decreased cognitive performance. Five out of the seven studies investigating daily functioning showed an association between comorbidity burden and decreased daily functioning. Neuropsychiatric symptoms (NPS) increased with increasing comorbidity burden in two out of three studies investigating NPS. Associations were predominantly found in studies analyzing the association cross-sectionally, in a time-varying manner or across short follow-up (≤2 years). Rarely baseline comorbidity burden appeared to be associated with outcomes in studies analyzing progression over longer follow-up periods (>2 years).ConclusionThis review provides evidence of an association between somatic comorbidities and multifaceted LOAD progression. Given that time-varying comorbidity burden, but much less so baseline comorbidity burden, was associated with the three dimensions prospectively, this relationship cannot be reduced to a simple cause-effect relation and is more likely to be dynamic. Therefore, both future studies and clinical practice may benefit from regarding comorbidity as a modifiable factor with a possibly fluctuating influence on LOAD.

Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes

“…9 Other studies have shown AD progression is likely to be influenced by noncognitive factors, such as depressive symptoms and comorbid disease burden as well. 6,7 These findings suggest that combining disease-related characteristics with other information on the patient's profile may improve the prediction of AD progression. Such a prediction may not only provide valuable prognostic information for patients and caregivers but also help us to target patients who are most likely to benefit from interventions aimed at slowing disease progression.…”

“…cognition), even though the importance of a multidomain approach in dementia has been repeatedly reinforced. 3, 5, 6 The few studies that have analyzed multiple outcomes of AD simultaneously, have shown correlation between rates of change in cognition and daily functioning. 2, 7, 8 …”

“…4 Most of these studies looked at one health dimension at a time (eg, cognition), even though the importance of a multidomain approach in dementia has been repeatedly reinforced. 3,5,6 The few studies that have analysed multiple outcomes of AD simultaneously have shown correlation between rates of change in cognition and daily functioning. 2,7,8 A literature review of factors associated with rapid cognitive decline in AD concluded that study results were heterogeneous and often contradictory.…”

Incidence and Predictors of Cognitive Frailty Among Older Adults: A Community-based Longitudinal Study

“…Nutritional status indicators were assessed using anthropometric measurements, including weight, height, arm span, waist circumference, hip circumference, mid-upper arm circumference (MUAC), and calf circumference. The measurement of these figures was done according to standard protocols [14]. The Body Mass Index (BMI, kg/m 2 ) was calculated as the body weight in kilograms divided by the squared standing height in meters.…”

“…The upstream causative mechanisms of physical frailty include systemic inflammation, cell senescence, hormonal changes, and mitochondrial dysfunction [11,12]. These mechanisms are reported to exacerbate neurodegenerative and vascular damages associated with cognitive decline and dementia [13,14].…”