Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations.

Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer's disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (rho = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD.

[Subfertility in mentally disabled people who desire to have children: how to give balanced advice]. / Kinderwens van verstandelijk beperkte ouders met subfertiliteit.

When people with a mental disability fail to conceive naturally, they also like to be considered for fertility treatment. However, the GP, gynaecologist or fertility specialist may question their parenting competence. Physicians may and can refuse fertility treatment if they have reasons to suspect that the child will have a poor quality of life. We are using a case history to outline how a well-considered multidisciplinary recommendation can be made that does justice to the patient's request while causing the least amount of grief. The guiding principle in doing so is the moral consideration that the harm to the future child should not outweigh the harm to the parents.

People with intellectual disability: what do we know about adulthood and life expectancy?

Increases in the life expectancy of people with Intellectual Disability have followed similar trends to those found in the general population. With the exception of people with severe and multiple disabilities or Down syndrome, the life expectancy of this group now closely approximates with that of the general population. Middle and old age, which until 30 years ago were not recognized in this population, are now important parts of the life course of these individuals. Older adults with Intellectual Disabilities form a small, but significant and growing proportion of older people in the community. How these persons grow older and how symptoms and complications of the underlying cause of the Intellectual Disability will influence their life expectancy is of the utmost importance.

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.

Stress and self-injurious behavior; hormonal and serotonergic parameters in mentally retarded subjects.

Self-injurious behavior (SIB) and stereotyped behavior (SB) are major challenges for professionals in the field of mental retardation. From animal experiments it has become obvious that these behavioral disturbances are not purposeless but may emerge secondary to restrictive environment and may serve de-arousing objectives. In mentally retarded subjects, several hypotheses have been formulated concerning the pathogenesis of SIB, particularly about the involvement of serotonin and beta-endorphin, which are supported by beneficial treatment effects of the opiate antagonist naltrexone and serotonin modulating compounds, respectively. The present study was designed to investigate basal levels of stress-hormonal and serotonergic parameters as well as plasma levels of amino-acids and the beta-carboline norharman in a group of 64 mentally retarded subjects with SB and/or SIB. Allocation to three different groups comprising 17 retarded controls, 26 subjects with mainly SIB and 21 subjects with mainly SB, was originally performed using the scores on the factors Irritability, Stereotypic Behaviour and Hyperactivity of the Aberrant Behavioral Checklist. Because of the overlapping nature of the behavioral parameters, subjects were subsequently divided into three maximally contrasting groups, viz. predominantly SIB, predominantly SB and retarded controls, each comprising 11 subjects. With respect to beta-endorphin, no differences were found either between both the original and maximally contrasting groups or in comparison to nonretarded controls. As compared to retarded controls, a tendency to lower values for total cortisol and cortisol binding globulin appeared to be present in the SIB group, whereas in the SB group a tendency toward higher levels of the major serotonin metabolite 5-HIAA was found. In the contrasting SB group, a trend toward decreased total cortisol level was observed as compared to the retarded control group. In addition, significantly lower values for norharman and tryptophan were demonstrated in the total group of mentally retarded subjects as compared to non-retarded controls. The results of the present study, yielding co-existent disturbances in stress-hormonal and monoaminergic mechanisms as well as in the metabolism of norharman, are in line with the hypothesis that mentally retarded subjects are at risk for the development of stress-related behavioral disorders such as SIB and SB.