Neuropsychiatric symptoms and Apolipoprotein E: Associations with eventual Alzheimer's disease development

Arch Gerontol Geriatr. Jul-Aug 2016;65:231-8. doi: 10.1016/j.archger.2016.04.006. Epub 2016 Apr 14.


Objective: Alzheimer's disease (AD) is the result of neurodegeneration, which manifests clinically as deficits in memory, thinking, and behavior. It was hypothesized that neuropsychiatric symptoms and the apolipoprotein E genotype increase the likelihood of Alzheimer's disease development.

Methods: Utilizing data from the National Alzheimer's Coordinating Center, information from evaluations of 11,453 cognitively intact participants was analyzed. Survival analysis was used to explore relationships between individual neuropsychiatric symptoms as determined by the Neuropsychiatric Inventory Questionnaire, apolipoprotein E, and eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic (additive and multiplicative) interactions.

Results: This study provided evidence for an increased hazard of developing AD among participants with any of the symptoms assessed by the NPI-Q. The hazard of developing AD was almost thirteen times higher for ε4 carriers with delusions and eleven times greater for those with apathy and disinhibition. Statistically significant hazards (p>0.001) were also realized by ε4 carriers with hallucinations; agitation; depression; anxiety; elation; apathy; irritability; and motor, sleep, and appetite disturbances.

Conclusions: Findings suggest that neuropsychiatric symptoms are associated with eventual AD diagnosis among a group of cognitively asymptomatic participants at baseline. Many studies begin with a group of participants already impacted by AD diagnosis. The longitudinal analysis of a group of participants who, at baseline, demonstrated no observable signs of AD was a strength of this study. This investigation contributes to the literature exploring an increased hazard of AD due to potential modifiable risk factors and genetic biomarkers such as apolipoprotein E.

Keywords: Agitation; Alzheimer’s disease; Anxiety; Apathy; Apoe ε4; Apolipropotein e; Appetite disturbance; Delusions; Disinhibition; Elation; Hallucinations; Irritability; Motor disturbance; Neuropsychiatric symptoms; Sleep disturbance.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology*
  • Anxiety / psychology
  • Apathy
  • Apolipoprotein E4 / genetics*
  • Delusions / psychology
  • Depression / psychology
  • Feeding and Eating Disorders
  • Female
  • Genotype
  • Heterozygote*
  • Humans
  • Irritable Mood
  • Male
  • Psychomotor Agitation
  • Sleep Wake Disorders / psychology


  • Apolipoprotein E4