Association between Neuropsychiatric Improvement and Neurocognitive Change in Alzheimer's Disease: Analysis of the CATIE-AD Study

J Alzheimers Dis. 2018;66(1):139-148. doi: 10.3233/JAD-180304.


Background/objective: To assess associations between improvements in neuropsychiatric symptoms (NPS) and neurocognitive change in patients with Alzheimer's disease (AD) during treatment using the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer Disease (CATIE-AD) dataset.

Methods: AD outpatients with NPS who needed pharmacological treatment (n = 421) were followed up with antipsychotics, citalopram, or placebo for up to 36 weeks (mean±SD = 252±52 days). The study aim was to investigate associations between improvement in each NPS evaluating scale (by Clinical Global Impression of Change [CGI-C], Neuropsychiatric Inventory [NPI], or Brief Psychiatric Scale [BPRS]) at endpoint (week 36 or early termination [ET], n = 340) and neurocognitive change (change score in the Mini-Mental State Examination [MMSE] between endpoint and baseline during the treatment). Multiple logistic regression analyses were performed on the associations between each NPS improvement and neurocognitive change as well as socio-clinico-demographic variables of interest.

Results: At endpoint, NPS improvement rates were 76.1%, 70.8%, and 58.1% in CGI-C, NPI, and BPRS, respectively, while MMSE score change was -2.3±3.8. NPS improvement was significantly related to more severe psychotic symptoms at baseline and preserved levels of neurocognition (smaller MMSE score change) among several variables.

Conclusions: Our findings suggested that neurocognitive preservation may be associated with attaining optimal benefits from any treatment against NPSs in a longitudinal treatment course of patients with AD.

Keywords: Alzheimer’s disease; CATIE-AD; antipsychotic; neurocognitive impairment; neuropsychiatric symptom.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology*
  • Antipsychotic Agents / therapeutic use
  • Cognition Disorders / diagnosis
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / psychology*
  • Double-Blind Method
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Disorders / diagnosis
  • Mental Disorders / drug therapy*
  • Mental Disorders / psychology*
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / psychology
  • Treatment Outcome


  • Antipsychotic Agents