Longitudinal Neuropsychiatric Predictors of Death in Alzheimer’s Disease

Abstract

Characteristics associated with life expectancy in Alzheimer's disease (AD) are still far from known. Here we aimed at examining the ability of baseline/longitudinal clinical variables to predict time to death. One-hundred fifty AD outpatients underwent diagnostic, neuropsychiatric, and functional assessment at baseline (when ApoE ɛ4 was also investigated) and at each subsequent annual visit. A random effects joint modeling approach was used to simultaneously model the baseline and longitudinal trajectory of each factor and predict the time to death, adjusting for demographic covariates. An ancillary analysis of ApoE ɛ4 status as a predictor was also conducted. Kaplan-Meier survival curves were constructed to elucidate the relationship between each factor and the estimated probability of death over time. Shorter survival was associated with male gender, higher education, older age, lower cognition, and worse functioning in daily life, but not ApoE ɛ4 status. Longitudinal trajectories increased predictive power over using just baseline levels highlighting apathy, and secondarily aberrant motor behaviors and sleep disorders, as a highly reliable predictor for mortality. Apathy was the strongest neuropsychiatric predictor of time to death, which supports its role in the pathogenesis of the disorder. An increased knowledge of factors modulating survival in AD is a strategic prerequisite to plan therapeutic interventions.

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

“…In the large retrospective cohort study comprising 5831 men and 17918 women, the shorter survival in men was explained by the increased number of co-morbidities in this group (cancer, arrhythmia, obstructive pulmonary disease, and Parkinson's disease [21]. High educational level appeared also as an indicator of worse outcomes [22,[31][32][33]. Vascular risk factors were associated with poorer outcomes in some studies [33][34][35][36] but not in another one [32].…”

“…In Table 2 are given the predictive factors of poorer outcomes in AD found in the different papers revised. Among demographic variables, there are four predictors that appeared consistently across many cohort studies: male gender [15][16][17][18][19][20][21][22][23] and extrapyramidal signs [24][25][26][27][28][29], which are associated with both shorter survival and faster cognitive decline. Only in one study the female gender was associated with poorer outcome [30].…”

Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases

“…Sleep disorders or nocturnal behavioral disturbances predispose to earlier nursing home placement [33,34], are associated with poorer functional status [35], and worsened cognitive function [36], and may predict earlier mortality [37].…”

Apathy is related to reduced activation in cognitive control regions during set‐shifting

“…Apathy is a prominent symptom in several neurological and psychiatric disorders, including Alzheimer's and Parkinson's disease, traumatic brain injury, schizophrenia, and major depressive disorder [Andersson et al, 1999;Cacciari et al, 2010;Dujardin et al, 2007;Foussias and Remington, 2010;Krishnan et al, 1995;Schooler et al, 2015;Spalletta et al, 2015]. Apathy refers to a quantitative reduction of voluntary and purposeful behaviors [Levy and Dubois, 2006].…”