Comorbidity and progression of late onset Alzheimer's disease

A systematic review

Miriam L. Haaksma, Lara R. Vilela, Alessandra Marengoni, Amaia Calderon-Larrañaga, Jeannie-Marie S Leoutsakos, Marcel G.M.Olde Rikkert, Rene J.F. Melis

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Article numbere0177044
JournalPLoS One
Volume12
Issue number5
DOIs
StatePublished - May 1 2017

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systematic review
Alzheimer disease
Comorbidity
Alzheimer Disease
cognition
Deterioration
comorbidity
Aptitude
observational studies
disease course
meta-analysis
Cognition
Observational Studies
Psychiatry
Disease Progression
Meta-Analysis
experimental design
deterioration
Outcome Assessment (Health Care)
Databases

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Haaksma, M. L., Vilela, L. R., Marengoni, A., Calderon-Larrañaga, A., Leoutsakos, J-M. S., Rikkert, M. G. M. O., & Melis, R. J. F. (2017). Comorbidity and progression of late onset Alzheimer's disease: A systematic review. PLoS One, 12(5), [e0177044]. https://doi.org/10.1371/journal.pone.0177044

Comorbidity and progression of late onset Alzheimer's disease : A systematic review. / Haaksma, Miriam L.; Vilela, Lara R.; Marengoni, Alessandra; Calderon-Larrañaga, Amaia; Leoutsakos, Jeannie-Marie S; Rikkert, Marcel G.M.Olde; Melis, Rene J.F.

In: PLoS One, Vol. 12, No. 5, e0177044, 01.05.2017.

Research output: Contribution to journalReview article

Haaksma, ML, Vilela, LR, Marengoni, A, Calderon-Larrañaga, A, Leoutsakos, J-MS, Rikkert, MGMO & Melis, RJF 2017, 'Comorbidity and progression of late onset Alzheimer's disease: A systematic review', PLoS One, vol. 12, no. 5, e0177044. https://doi.org/10.1371/journal.pone.0177044
Haaksma ML, Vilela LR, Marengoni A, Calderon-Larrañaga A, Leoutsakos J-MS, Rikkert MGMO et al. Comorbidity and progression of late onset Alzheimer's disease: A systematic review. PLoS One. 2017 May 1;12(5). e0177044. https://doi.org/10.1371/journal.pone.0177044
Haaksma, Miriam L. ; Vilela, Lara R. ; Marengoni, Alessandra ; Calderon-Larrañaga, Amaia ; Leoutsakos, Jeannie-Marie S ; Rikkert, Marcel G.M.Olde ; Melis, Rene J.F. / Comorbidity and progression of late onset Alzheimer's disease : A systematic review. In: PLoS One. 2017 ; Vol. 12, No. 5.
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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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N2 - 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.

AB - 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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