The APOE ε4 allele is associated with increased frontally mediated neurobehavioral symptoms in amnestic MCI.

The apolipoprotein E ε4 allele is a risk factor for late-onset Alzheimer disease (AD), and the frontal lobes may be among the regions that manifest effects of ε4 even early in the disease. We predicted that among patients with amnestic mild cognitive impairment (aMCI) and AD, ε4 would be associated with increased neurobehavioral symptoms when assessed using a measure sensitive to frontal lobe integrity. We obtained cognitive data and caregiver ratings on the Frontal Systems Behavior Scale (FrSBe) for aMCI patients (N=29 ε4 carriers; N=29 noncarriers) and AD patients (N=47 carriers; N=42 noncarriers). In both diagnostic groups, ε4 carriers had lower scores on tests of memory but did not differ on cognitive screening measures or tests of executive functioning. There were no differences in retrospective caregiver ratings of preillness status on the FrSBe by ε4 status in either diagnostic group. However, in the aMCI group, ε4 carriers had elevated current FrSBe Executive Dysfunction scores in comparison with noncarriers. In the AD group, there were no differences in current FrSBe scores by genotype group. Results indicate that ε4-related behavior change occurs in the aMCI stage but may not be apparent by the AD stage.