ABSTRACT
Apolipoprotein E (APOE) is consistently associated with dementia in the general population. Findings on the role of this gene in persons with Down's syndrome (DS) are inconclusive. We studied the effects of APOE on mortality and dementia in a longitudinal prospective study of a large population-based sample of persons with DS (n=425), demented and non-demented. There was evidence that APOE epsilon4 is correlated with the rate of decline in the social competence rating scale (SRZ) (p=0.04). In our population, we found overall a modest but not statistical significant effect on the prevalence of dementia (OR=1.57, 95%CI: 0.87-2.82). We did observed a significant long-term effect on the incidence of dementia (HR=4.66, 95%CI: 1.35-16.14), but for those with a follow-up less than 3 years the risk was not significantly increased: HR=0.83 (95%CI 0.35-1.94). When pooling our data in a meta-analysis, the APOE epsilon4 allele shows a 1.59-fold (95%CI: 1.19-2.12) increase in risk of dementia in persons with DS. We conclude that APOE is influencing the risk of dementia in persons with DS.
Subject(s)
Apolipoproteins E/genetics , Dementia/epidemiology , Dementia/genetics , Down Syndrome/epidemiology , Down Syndrome/genetics , Risk Assessment/methods , Aged , Aged, 80 and over , Comorbidity , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Netherlands/epidemiology , Prevalence , Risk FactorsABSTRACT
BACKGROUND: Numerous studies have documented that persons with Down's syndrome (DS) are at an increased risk of Alzheimer's disease (AD). However, at present it is still not clear whether or not all persons with DS will develop dementia as they reach old age. METHODS: We studied 506 people with DS, aged 45 years and above. A standardized assessment of cognitive, functional and physical status was repeated annually. If deterioration occurred, the patients were examined and the differential diagnosis of dementia was made according to the revised Dutch consensus protocol and according to the ICD-10 Symptom Checklist for Mental Disorders. We compared our findings with those reported in the literature. RESULTS: The overall prevalence of dementia was 16.8%. Up to the age of 60, the prevalence of dementia doubled with each 5-year interval. Up to the age of 49, the prevalence is 8.9%, from 50 to 54, it is 17.7%, and from 55 to 59, it is 32.1%. In the age category of 60 and above, there is a small decrease in prevalence of dementia to 25.6%. The lack of increase after the age of 60 may be explained by the increased mortality among elderly demented DS patients (44.4%) in comparison with non-demented patients (10.7%) who we observed during a 3.3-year follow-up. There was no decrease in incidence of dementia in the age group of 60 and above. Our findings are very similar to those published in the literature. Patients with dementia were more frequently treated with antiepileptic, antipsychotic and antidepressant drugs. The history of depression was strongly associated with dementia. CONCLUSIONS: Our study is one of the largest population-based studies to date. We found that despite the exponential increase in prevalence with age, the prevalence of dementia in the oldest persons with DS was not higher than 25.6%.
