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.
Highlights
Dementia is typically defined as a clinical syndrome of cognitive decline that is sufficiently severe to interfere with social or occupational functioning [1]
This review provides evidence of an association between somatic comorbidities and multifaceted late-onset Alzheimer’s disease (LOAD) progression
Comorbid disease burden was measured using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) [25], Charlson Comorbidity Index (CCI) [26], General Medical Health Rating (GMHR) [15] and some studies counted the comorbidities based on hospital records, physical examination and/ or patient/caregiver report
Summary
Dementia is typically defined as a clinical syndrome of cognitive decline that is sufficiently severe to interfere with social or occupational functioning [1]. It is an umbrella term for a group of cognitive disorders characterized by progressive decline in cognitive function interfering with independently carrying out activities of daily life due to brain damage or disease, but not related to delirium or depression [2]. Alzheimer’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)
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