title: 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.
authors.affiliation: IRCCS Santa Lucia Foundation, Rome, Italy.|Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.|Department of Biostatistics, University of Iowa, Iowa City, IA, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Robinson
authors.affiliation: ASL1 Umbria, Perugia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Trequattrini
authors.affiliation: IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pizzoli
authors.affiliation: IRCCS Santa Lucia Foundation, Rome, Italy.|Department of Medicine of Systems, Tor Vergata University, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Orfei
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000401:mortality* / Q000523:psychology*; D053327:Apolipoprotein E4 / Q000235:genetics; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011379:Prognosis
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer’s disease; apathy; mortality; predictors; prognosis