The impact of apolipoprotein E on dementia in persons with Down's syndrome.

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.

Prospective study of the prevalence of Alzheimer-type dementia in institutionalized individuals with Down syndrome.

Institutionalized patients with Down syndrome (n = 307) were monitored for 5 to 10 years prospectively to determine prevalence of Alzheimer-type dementia. Clinical signs, cognitive functioning, and EEGs were assessed. When possible, postmortem neuropathological examinations were conducted. Progressive mental and physical deterioration was found for 56 of the residents. Mean age at onset of dementia was 56 years. Prevalence increased from 11% between ages 40 and 49 to 77% between 60 and 69. All patients 70 and over had dementia. Neuropathological findings were consistent with clinical diagnosis. Use of a dementia checklist, cognitive skills inventory, and EEG reliably detected Alzheimer-type dementia at an early stage.

Use of electroencephalography to detect Alzheimer's disease in Down's syndrome.

We studied the role of electroencephalography (EEG) in the diagnosis of Alzheimer-type dementia in patients with Down's syndrome. 197 patients with Down's syndrome were monitored for 5 to 8 years. Aspects of cognitive functioning were assessed twice yearly. EEGs were scored in a blind fashion, and changes in the EEG were compared to changes in cognitive functioning. When possible, a neuropathological post-mortem examination was performed. Cognitive functioning was drastically reduced in 29 patients. The dominant occipital rhythm became slower at the onset of the cognitive deterioration, and eventually disappeared. In 11 of these patients neuropathological examination showed a severe form of Alzheimer's disease. Changes in the frequency of the dominant occipital rhythm could distinguish between Alzheimer's disease or other causes as underlying the cognitive decline. Slowing of the dominant occipital rhythm seems to be related to Alzheimer's disease in patients with Down's syndrome, and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration. The EEG is thus an important tool in the clinical diagnosis of Alzheimer-type dementia in patients with Down's syndrome.

Influence of aging and neurodegenerative disease on changes in band 3-like proteins in white blood cells.

Fluorescent microspheres were used to measure antibody-induced capping of leukocyte membrane proteins that are immunologically related to band 3, the anion exchanger of the erythrocyte. The degree of capping was found to increase with donor age. Surface labeling and capping characteristics of cells from healthy, age-matched controls were not different from those from patients with Alzheimer's disease, multi-infarct dementia, and Down's syndrome. Immunoblots, however, indicated increased expression and/or breakdown of band 3-like proteins in leukocytes from patients when compared with young and old control donors. These findings emphasize the possible involvement of band 3-like proteins of nucleated cells in aging and disease.

Erythrocyte membrane changes of individuals with Down's syndrome in various stages of Alzheimer-type dementia.

An increase in erythrocyte-bound IgG, enhanced breakdown of band 3, and changes in erythrocyte anion transport characteristics are observed in individuals with Down's Syndrome. We interpret these data as indicative for a disturbance of normal erythrocyte aging. A comparison of three groups of individuals with Down's Syndrome in various stages of dementia of the Alzheimer type did not reveal a correlation between the erythrocyte membrane changes and age or stage of dementia. Considering previously obtained data on patients with senile dementia of the Alzheimer type (7), these results may signify that parameters of disturbed erythrocyte aging represent presymptomatic markers of Alzheimer-type dementia.

[Dementia symptoms in Down's syndrome in a residentially treated group of mentally handicapped]. / Het vóórkomen van dementiële beelden bij het syndroom van Down in een residentieel verzorgde groep zwakzinnigen.

In a controlled retrospective study of 27 Down patients the occurrence of the neuropathological signs of Alzheimer's disease was investigated. The patients were divided into two groups: group I with neuropathologically proven Alzheimer and group II without Alzheimer's disease. All patients of group I had been older than 54 years at death, while all patients of group II were younger. All patients of group I suffered from severe dementia, none of group II did. The early clinical symptoms, changes in social competence and EEG alterations were combined in a dementia detection method suitable for mentally deficient patients.