Prospective belgian study of neurodegenerative and vascular dementia: APOE genotype effects

Abstract

Objective: The authors conducted a prospective study of neurodegenerative and vascular dementia in Belgium. Strict diagnostic inclusion criteria were used to include well defined patients and controls. The results of apolipoprotein E (APOE) genotype effect on risk and clinical characteristics are presented. Methods: APOE genotyping was performed in patients with probable Alzheimer's disease (AD) (n=504), fronto-temporal dementia (FTD) (n=47), vascular dementia (VaD) (n=152), mixed dementia (n=132), mild cognitive impairment (MCI) (n=44), Parkinson's disease (PD) (n=30), dementia with Lewy bodies (DLB)(n=17), and multisystem atrophy (MSA)/progressive supranuclear palsy (PSP) (n=12). Results: The APOE allele frequencies of this Belgian control population (∈2: 6.9%; ∈3: 76.2%; ∈4: 16.9%) did not differ from those reported for other white populations. AD, MCI, and mixed dementia patients had higher APOE ∈4 (32.9%, 38.6%, and 28.4% respectively) and lower APOE ∈3 (62.2%, 53.4%, and 66.3%) frequencies compared with controls, whereas only AD and mixed dementia patients had lower APOE ∈2 frequencies (4.9% and 5.3%). Apart from a borderline significant different distribution of APOE allele frequencies in VaD patients compared with controls, no other differences were detected. The influence of APOE ∈4 on clinical features of dementia was limited to lower age at onset in AD patients and a less pronounced negative correlation between age at onset and number of ∈4 alleles in MCI and mixed dementia patients. Conclusions: This study confirmed the risk association between APOE ∈4 and AD. The observation that APOE ∈4 is associated with mixed dementia reflected the role of AD in the aetiopathogenesis of this condition. Although MCI is an aetiologically heterogeneous syndrome, the increased APOE ∈4 frequencies indicated that a large proportion of the MCI patients included in the study might be predisposed to develop AD.