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. 2017 May 4;12(5):e0177044.
doi: 10.1371/journal.pone.0177044. eCollection 2017.

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

Miriam L Haaksma  1   2 , Lara R Vilela  1   2 , Alessandra Marengoni  3   4 , Amaia Calderón-Larrañaga  3   5   6 , Jeannie-Marie S Leoutsakos  7 , Marcel G M Olde Rikkert  1   2 , René J F Melis  1   2
Affiliations

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

Miriam L Haaksma et al. PLoS One. .

Abstract

Background: 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).

Methods: We 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.

Results: Nine 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).

Conclusion: This 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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

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References

    1. Leoutsakos JM, Forrester SN, Corcoran CD, Norton MC, Rabins PV, Steinberg MI, et al. Latent classes of course in Alzheimer's disease and predictors: the Cache County Dementia Progression Study. Int J Geriatr Psychiatry. 2015;30(8):824–32. doi: 10.1002/gps.4221 - DOI - PMC - PubMed
    1. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's dement. 2011;7(3):263–9. - PMC - PubMed
    1. Peavy GM, Jacobson MW, Salmon DP, Gamst AC, Patterson TL, Goldman S, et al. The Influence of Chronic Stress on Dementia-Related Diagnostic Change in Older Adults. Alzheimer Dis Assoc Disord. 2012;26(3):260–6. doi: 10.1097/WAD.0b013e3182389a9c - DOI - PMC - PubMed
    1. Green C, Zhang S. Predicting the progression of Alzheimer's disease dementia: A multidomain health policy model. Alzheimer's dement. 2016;12(7):776–85. - PMC - PubMed
    1. Satizabal CL, Beiser AS, Chouraki V, Chene G, Dufouil C, Seshadri S. Incidence of Dementia over Three Decades in the Framingham Heart Study. The New England journal of medicine. 2016;374(6):523–32. doi: 10.1056/NEJMoa1504327 - DOI - PMC - PubMed

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