APOE-ε4 in age-related memory complaints and Alzheimer's disease

APOE-ε4 has been consistently found to be frequent in patients with senile dementia of the Alzheimer type (SDAT). Since forgetfulness may represent an early stage of dementia, APOE-ε4 frequency can be expected to be high in such subjects, particularly in those who later develop dementia. We examined here the proportion of ε4 alleles in patients with SDAT (n = 179), controls (n = 154) and subjects with age-related memory complaints (ARMC, n = 167); 16 of them developed dementia of Alzheimer type and three of them dementia of vascular type. We also evaluated the relative risk of dementia (of Alzheimer type) in ARMC subjects who are ε4-carriers, using a Cox proportional hazards model. The APOE-ε4 allele frequency was 27% in SDAT, 25% in ARMC patients who became demented, 15% in ARMC subjects who remained such after at least 1 year of follow-up, and 10% in controls. APOE-ε4 allele was significantly more frequent in SDAT than in controls or than in stable ARMC (OR = 3.7 [2-6.3] and OR = 2.5 [1.5-4], respectively, p < 0.01). The risk of dementia in ARMC subjects carrying an ε4 allele was three-fold that of those without (expβ = 3.1 [0.98-10], p = 0.05). Older age at onset of memory decline and lower minimental scores at initial visit were also associated with development of dementia in ARMC subjects (exp β = 1.1 [1.0-1.2], p = 0.05 and exp = 0.76 [0.6-0.9]), p = 0.008). In conclusion, the APOE-ε4 allele was found to occur frequently in ARMC who subsequently develop dementia, therefore it can indicate a predisposition for dementia in such patients.