Neuropsychiatric symptoms, apolipoprotein E gene, and risk of progression to cognitive impairment, no dementia and dementia: the Aging, Demographics, and Memory Study (ADAMS)

Int J Geriatr Psychiatry. 2013 Jul;28(7):672-80. doi: 10.1002/gps.3868. Epub 2012 Aug 23.


Objective: To examine the relationship of neuropsychiatric symptoms and apolipoprotein E (APOE) ε4 allele status to dementia at baseline and progression to dementia in older adults with and without cognitive impairment, no dementia (CIND).

Methods: Adults (n = 856) 71 years and older (mean age = 79.15 years), 12.8% ethnic minority and 60.6% women, completed neuropsychological tests and APOE genotyping, and a proxy informant completed the Neuropsychiatric Inventory.

Results: After adjusting for age and education, neuropsychiatric symptoms and APOE ε4 were independently associated with CIND and dementia status at baseline (compared with cognitively normal). Further, neuropsychiatric symptoms predicted progression to dementia at 16- to 18-month follow-up among participants with CIND at baseline; the presence of these symptoms decreased the risk of progression from normal to CIND or dementia at 36 to 48 months.

Conclusion: Findings provide cross-sectional and longitudinal support for the role of neuropsychiatric symptoms in the prediction of cognitive impairment, particularly dementia. APOE ε4, although important, may be a less robust predictor. This investigation highlights the importance of behavioral symptoms, such as neuropsychiatric symptom status or frequency/severity, as predictors of future cognitive decline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics*
  • Cognition Disorders* / genetics
  • Cognition Disorders* / psychology
  • Cross-Sectional Studies
  • Dementia* / genetics
  • Dementia* / psychology
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Psychiatric Status Rating Scales


  • Apolipoprotein E4