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Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia: a population-based study

Anna Pink1, Gorazd B Stokin1, Mairead M Bartley1

  • 1From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.

Neurology
|February 6, 2015
PubMed
Abstract

Insights

Certain neuropsychiatric symptoms, like depression and apathy, combined with the APOE ε4 gene variant, significantly increase dementia risk in individuals with mild cognitive impairment (MCI). This highlights a synergistic effect impacting disease progression.

Area of Science:

  • Neuroscience and Neurology
  • Gerontology
  • Genetics and Epidemiology

Background:

  • Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia.
  • The apolipoprotein E ε4 (APOE ε4) allele is a known genetic risk factor for Alzheimer's disease.
  • Neuropsychiatric symptoms are common in MCI and may influence dementia conversion.

Purpose of the Study:

  • To examine the interplay between APOE ε4 genotype and neuropsychiatric symptoms in predicting dementia risk.
  • To investigate the association of specific neuropsychiatric symptoms with incident dementia in individuals with prevalent MCI.
  • To determine if APOE ε4 modifies the effect of neuropsychiatric symptoms on dementia risk.

Main Methods:

  • Prospective cohort study of 332 participants (≥70 years) with prevalent MCI from the Mayo Clinic Study of Aging.
  • Median follow-up of 3 years, with MCI and dementia diagnoses confirmed by expert consensus.
  • Baseline assessment of neuropsychiatric symptoms using the Neuropsychiatric Inventory Questionnaire; Cox proportional hazards models adjusted for covariates.

Main Results:

  • Agitation, nighttime behaviors, depression, and apathy at baseline were associated with increased dementia risk.
  • Significant additive interaction observed between APOE ε4 and depression (HR=2.21) and between APOE ε4 and apathy (HR=1.93).
  • Anxiety, irritability, and appetite changes did not show a significant association with incident dementia.

Conclusions:

  • In individuals with MCI, specific neuropsychiatric symptoms (agitation, nighttime behaviors, depression, apathy) predict higher dementia risk.
  • A synergistic interaction exists between APOE ε4 and depression or apathy, amplifying dementia risk.
  • These findings underscore the importance of addressing neuropsychiatric symptoms in MCI management and risk prediction.

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