Dose dependent effect of APOE epsilon4 on behavioral symptoms in frontal lobe dementia

Neurobiol Aging. 2006 Feb;27(2):285-92. doi: 10.1016/j.neurobiolaging.2005.02.005.


To determine whether apolipoprotein alleles (APOE) influence behavioral and psychological signs and symptoms of dementia (BPSD), we initiated a prospective, longitudinal study. Patients with Alzheimer's disease (AD) (N=186), frontotemporal dementia (FTD) (N=29), mixed dementia (MXD) (N=28), dementia with Lewy bodies (DLB) (N=11) and Parkinson's disease dementia (PDD) (N=7) were included. Blood was collected for DNA extraction and APOE genotyping. Behavioral assessments were performed at baseline and semi-annually thereafter, using behavioral assessment scales (Middelheim frontality score, behavioral pathology in Alzheimer's disease rating scale (Behave-AD)). In FTD patients, we identified dose dependent effects of APOE epsilon4 on the Behave-AD total and cluster aggressiveness scores. APOE epsilon2 was associated with a higher score on the Behave-AD cluster delusions in PDD/DLB patients. No APOE effects on frequency or severity of BPSD in AD and MXD patients were found. In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE epsilon4 with aggression (FTD) and of APOE epsilon2 with delusions (PDD/DLB).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Analysis of Variance
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Behavioral Symptoms* / etiology
  • Behavioral Symptoms* / genetics
  • Behavioral Symptoms* / pathology
  • Dementia / classification
  • Dementia / genetics*
  • Dementia / pathology*
  • Demography
  • Female
  • Frontal Lobe / pathology*
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Status Schedule / statistics & numerical data
  • Middle Aged


  • Apolipoprotein E4
  • Apolipoproteins E