Researchers have already established that the Apolipoprotein E epsilon 4 (APOE E4) allele is a risk factor for Alzheimer’s disease. In addition, research has implicated APOE E4 in frontotemporal dementia, dementia with Lewy bodies, and possibly Parkinson’s disease with dementia.

APOE alleles may also be involved in the clinical expression of these disorders. Carriers of the APOE E4 allele have an earlier age of onset in both Alzheimer’s disease and frontotemporal dementia. To date, however, studies evaluating the possible association between APOE alleles and behavioral and psychological signs and symptoms of dementia have been mixed. In addition, there have been no studies looking at the possible effect of APOE genotypes in patients with frontotemporal dementia, dementia with Lewy bodies, or Parkinson’s disease with dementia.

Accordingly, Dr. Engelborghs and colleagues performed a study of APOE genotyping in patients with a variety of dementias. This included 186 patients with Alzheimer’s disease, 29 patients with frontotemporal dementia, and 28 with mixed dementia. There were also 11 patients who had dementia with Lewy bodies, and 7 with Parkinson’s disease with dementia.

At baseline, all patients underwent interviews with caregivers to determine behavioral and psychological signs and symptoms since onset of dementia. Researchers assessed subjects using the Middelheim Frontality Score and Behave-AD monthly for 6 months, then twice per year after that.

Here at IPA, Dr. Engelborghs reported that the Alzheimer’s disease patients had a significantly higher frequency of APOE E4 alleles compared with historical controls. For the other groups of patients, there was no significant distribution toward any particular allele frequency.

One of the main statistical analyses in the study looked at potential sources of variation in behavioral and psychological test scores, including APOE genotype, as well as presence and number of APOE E2, E3 or E4 alleles.

In the Alzheimer’s disease and mixed dementia groups, there was no statistically significant interaction between these factors and test scores. However, in the frontotemporal dementia group, statistically significant sources of variation on test scores included APOE genotype, presence of APOE E2 allele, and number of APOE E4 alleles. In addition, a pooled analysis of the Parkinson’s disease with dementia/dementia with Lewy bodies group suggested that presence and number of APOE E2 alleles were significant sources of variation on test scores.

In a post-hoc analysis of the frontotemporal dementia group only, patients with an APOE 44 genotype had a significantly higher Behave-AD aggression cluster score versus the patients with an APOE 22 genotype. In addition, total Behave-AD scores were significantly higher in the APOE 44 genotype group.

Also in the frontotemporal dementia group, subjects carrying 2 APOE E4 alleles had higher scores on the Behave-AD aggression cluster and total scores than subjects with only 1 E4 allele. Analysis also revealed a statistically significant correlation between the number of E4 alleles and several specific Behave-AD scores.

Dr. Engelborghs said this study shows significant associations between the APOE E4 allele and behavioral and psychological signs and symptoms of dementia in patients with frontotemporal dementia. There was no association between APOE and the Middleheim Frontality Score, which indicates frontal lobe symptoms.

By contrast, researchers found no association between Alzheimer’s disease and behavioral and psychological signs and symptoms of dementia. This is in accordance with the majority of previous publications on this subject.

Finally, researchers observed a correlation between the E4 allele and signs and symptoms in patients with either Parkinson’s disease with dementia or dementia with Lewy bodies. However, the small sample size did not allow these patient groups to be analyzed separately. Therefore, researchers will need to confirm these findings in larger patient populations.