Longitudinal Neuropsychiatric Predictors of Death in Alzheimer's Disease

Gianfranco Spalletta, Jeffrey D. Long, Robert G. Robinson, Alberto Trequattrini, Sonia Pizzoli, Carlo Caltagirone, Maria D. Orfei

Research output: Contribution to journalArticlepeer-review


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 ε4 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 ε4 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 ε4 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.

Original languageEnglish
Pages (from-to)627-636
Number of pages10
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - Oct 1 2015


  • Alzheimer's disease
  • apathy
  • mortality
  • predictors
  • prognosis

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology


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