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Determinants of Progression and Mortality in Alzheimers disease: A Systematic Review

Author(s): Pedro J Modrego, Antonio Lobo


Neuropsychiatric symptoms (NPS) have been regarded as predictors of poor outcomes, and the use of neuroleptics as well, but with contradictory results. The objective of this article is to perform a systematic review of published works dealing with progression and survival in AD.


We searched articles aimed at determining the factors predicting faster cognitive decline and mortality in AD, published from January 1987 to April, 2018. We gave priority to prospective and retrospective cohorts analysing the influence of gender, NPS, neuropsychological predictors, co morbidities, and the use of neuroleptics/ antidepressants. The data-sources were 42 prospective cohorts including 24,711 patients; Hazard ratios/relative risks of mortality and faster cognitive decline were obtained for NPS and the use of psychotropic drugs. The risk of mortality for neuroleptics and ChEI was also obtained from 7 retrospective cohorts totalling 242,013 patients followed up.


High levels of NPS were predictors of both mortality and faster cognitive decline Considered in isolation, agitation/aggression, hallucinations, and depression predicted mortality. However the results for apathy and psychosis/delusions varied across the studies. According to prospective cohort studies there is no clear evidence that neuroleptics increase mortality. The use of neuroleptics is associated with faster cognitive deterioration. Conventional neuroleptics for NPS did not result in lower mortality rates than the atypical ones.


The presence of NPS is associated with poor outcomes in AD such as mortality and greater cognitive decline. Atypical neuroleptics do not shorten survival but are associated with faster cognitive decline

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