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.

The 'Journal of Comorbidity' is changing its name to the 'Journal of Multimorbidity and Comorbidity'. This may seem redundant, as many see 'comorbidity' and 'multimorbidity' as interchangeable terms. We believe it is important to highlight the distinction given the differences in how healthcare systems view patients with multiple chronic conditions (MCCs), and the important differences that arise in research and intervention development for these patients.In 1970, Feinstein first coined the term 'comorbidity' to describe 'Any distinct additional entity that has existed or may occur during the clinical course of a patient who has the index disease under study'. 1 From 1976, 2,3 the term 'multimorbidity' was increasingly used by health researchers to describe patients with MCCs. Due to the growing ambiguity around the use of the terms comorbidity and multimorbidity, in 1996 van den Akker et al. suggested clear definitions for both terms. 4 They suggested that comorbidity be defined according to Feinstein's original definition and multimorbidity be defined as 'the cooccurrence of multiple chronic or acute diseases and medical conditions within one person'. 4 In 2010, Boyd and Fortin provided a simpler definition of multimorbidity: 'the co-existence of two or more chronic conditions, where one is not necessarily more central than the others'. 5