Association Between Comorbidity Burden and Rapid Cognitive Decline in Individuals with Mild to Moderate Alzheimer's Disease

Aubert, Lauren; Pichierri, Sophie; Hommet, Caroline; Camus, Vincent; Berrut, Gilles; Decker, Laure de

doi:10.1111/jgs.13314

Cited by 35 publications

(37 citation statements)

References 26 publications

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“…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].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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“…In addition, the majority of AD cases frequently suffer from multiple complications (e.g., DM, other neurodegenerative disorders, cardiovascular diseases, and renal diseases). These comorbidities can enhance the complexity that underlies AD pathogenesis [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

Sun

et al. 2020

Journal of Diabetes Research

121

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As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer’s disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body’s diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain’s metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-β (Aβ) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aβ production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aβ pathology.

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“…The link between cognitive decline and physical comorbidities in AD has been substantially reported so far [11–14]. People with more comorbidities had more rapid deterioration in cognition and also showed significantly faster decline in daily functioning [15–17]. It has been shown that the effect of physical activity and exercise might be effective on cognitive function [18] and thus the decline in daily functioning due to cognitive deterioration could raise physical comorbidities in older subjects.…”

Section: Discussionmentioning

confidence: 93%

Donepezil may reduce the risk of comorbidities in patients with Alzheimer's disease: A large‐scale matched case‐control analysis in Japan

Kobayashi

Arai

2018

A&D Transl Res & Clin Interv

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IntroductionFew studies have focused on the association between donepezil and physical comorbid conditions in Alzheimer's disease patients.MethodsWe investigated the association between donepezil prescription and the occurrences of comorbidities in Alzheimer's disease patients, by using an electronic medical records database which contains case-based information on approximately three million patients from more than 60 hospitals across Japan.ResultsNine thousand seven hundred forty-nine patients had at least one diagnosis of Alzheimer's disease between 2001 and 2015. To test the robustness of the results, we used a risk set sampling method, and the matched cohorts based on age, sex, comorbidity level, and duration of illness consisted of 1406 cases and an equal number of controls. From the multivariate logistic regression analysis adjusted for covariance, less occurrence of physical comorbidities was associated with donepezil prescription in the matched cohort.DiscussionAlthough the mechanisms are unknown, donepezil may have positive effects on both cognition and physical status.

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Association Between Comorbidity Burden and Rapid Cognitive Decline in Individuals with Mild to Moderate Alzheimer's Disease

Abstract: Comorbidity burden was associated with rapid cognitive decline in subjects with AD.

Cited by 35 publications

References 26 publications

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

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

Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

Donepezil may reduce the risk of comorbidities in patients with Alzheimer's disease: A large‐scale matched case‐control analysis in Japan

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