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APOE-e4 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-e4 frequency can be expected to be high in such subjects, particularly in those who later develop dementia. We examined here the proportion of e4 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 e4-carriers, using a Cox proportional hazards model. The APOE-e4 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-e4 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 e4 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-e4 allele was found to occur frequently in ARMC who subsequently develop dementia, therefore it can indicate a predisposition for dementia in such patients.

The apolipoprotein E (APOE) epsilon 4 allele has been consistently found to be frequent in patients with progressive degenerative dementia of the Alzheimer type (DAT). Vascular dementia (VD) may occur as strokes superimposed on presymptomatic DAT, in which case APOE-epsilon 4 frequency should also be increased in VD. We have examined the distribution of APOE-epsilon 4 in patients with DAT (n = 176) or VD (n = 74) and controls (n = 133), and evaluated the risk of dementia associated with APOE-epsilon 4. APOE-epsilon 4 allele frequency was 27% in DAT patients, 21% in VD patients, and 11% in controls. The difference in the distribution of the epsilon 4 allele between DAT or VD patients and controls was statistically significant (chi(2) test, p < 0.05), with a 3.6- and 2.1-fold risk of dementia in DAT and VD patients carrying an epsilon 4 allele. The result that the APOE-epsilon 4 allele is more frequent in DAT patients than in controls, with VD patients falling in between, is consistent with the assumption that VD is a heterogeneous condition, with some patients having an underlying preclinical brain degeneration, in whom the dementia was precipitated by strokes.

The apolipoprotein E (APOE) epsilon 4 allele has been consistently found to be frequent in patients with progressive degenerative dementia of the Alzheimer type (DAT). Vascular dementia (VD) may occur as strokes superimposed on presymptomatic DAT, in which case APOE-epsilon 4 frequency should also be increased in VD. We have examined the distribution of APOE-epsilon 4 in patients with DAT (n = 176) or VD (n = 74) and controls (n = 133), and evaluated the risk of dementia associated with APOE-epsilon 4. APOE-epsilon 4 allele frequency was 27% in DAT patients, 21% in VD patients, and 11% in controls. The difference in the distribution of the epsilon 4 allele between DAT or VD patients and controls was statistically significant (chi(2) test, p0.05), with a 3.6- and 2.1-fold risk of dementia in DAT and VD patients carrying an epsilon 4 allele. The result that the APOE-epsilon 4 allele is more frequent in DAT patients than in controls, with VD patients falling in between, is consistent with the assumption that VD is a heterogeneous condition, with some patients having an underlying preclinical brain degeneration, in whom the dementia was precipitated by strokes.