Plasma beta-amyloid and duration of Alzheimer's disease in adults with Down syndrome.

OBJECTIVES: To investigate the relation of plasma levels of Abeta peptides (Abeta1-40 and Abeta1-42) and apolipoprotein E (APOE) genotype to dementia status, and the duration of Alzheimer's disease (AD) in adults with Down syndrome (DS). METHODS: Adults with DS were recruited from community settings and followed up for a mean period of 6.7 years. Plasma levels Abeta1-40 and Abeta1-42 and APOE genotype were determined at the last visit. RESULTS: There were 83 nondemented participants and 44 participants with prevalent AD. Overall, plasma levels of Abeta1-42, Abeta1-40 and the ratio Abeta1-42/Abeta1-40 did not differ significantly between the adults with DS. Among demented participants, the mean level of Abeta1-40 was significantly lower (157.0 vs. 195.3) and the ratio of Abeta1-42/Abeta1-40 was significantly higher (0.28 vs. 0.16) in those with more than 4 years duration of dementia than in those with 4 or fewer years' duration of dementia. This pattern was generally similar in those with and without an APOE epsilon4 allele. CONCLUSIONS: There is an association between plasma Abeta peptide levels and the duration of AD in older persons with DS. The predictive and diagnostic roles of Abeta1-42 and Abeta1-40 measurements for AD, however, remain controversial. Change in Abeta peptide levels with onset of AD and with the duration of dementia may account for a lack of difference between prevalent cases and nondemented individuals and for variation in the predictive power of Abeta peptide levels.

Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down syndrome.

OBJECTIVE: Virtually all adults with Down syndrome (DS) have neuropathological manifestations of Dementia in Alzheimer's disease (DAD) but not all develop clinical psychopathology. The effect of allelic variants of Apolipoprotein (APOE) gene in development and progression of DAD and mortality in persons with DS is examined. METHODS: Recruited participants with DS underwent two to 14 sequential assessments over a follow up period of 6 years on average and their APOE genotype determined. Dementia status was confirmed as recommended by the Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability. RESULTS: APOE genotype results were available for 252 individuals. Participants with APOE epsilon 4 allele had significantly higher risk of developing DAD (HR = 1.8, 95% CI: 1.12-2.79), had an earlier onset of DAD (55.0 vs 57.0 years; p = 0.0027) and a more rapid progression to death compared with participants with epsilon 3 allele (4.2 years vs. 5.4 years, respectively, p = 0.048). In non-demented persons with DS, epsilon 4 allele was associated with earlier death by 17 years (mean survival age, 55.7 vs. 72.7 years; HR = 5.9, 95% CI: 1.7-21.3). CONCLUSIONS: This study highlights the relationship of APOE genotype to morbidity and mortality in persons with DS which has important clinical implications. We recommend screening for APOE genotype in persons with DS to identify those at risk of DAD and premature death. Further research is required to investigate the underlying reasons for the early mortality in non-demented DS persons with an epsilon 4 allele.

Total serum cholesterol levels and Alzheimer's dementia in patients with Down syndrome.

BACKGROUND: The risk for dementia in Alzheimer's disease (DAD) in adults with Down syndrome (DS) is higher than in the general adult population. Hypercholesterolaemia has been reported as a risk factor for DAD in the general population. This study investigated the role of serum cholesterol levels in the onset of DAD in the DS population. METHODS: This study investigated total serum cholesterol levels in 179 DS persons (with and without DAD). The possible association between Apolipoprotein E and amyloid beta1-40 and beta1-42 levels was also investigated. RESULTS: No statistically significant association was found between total serum cholesterol levels and dementia in AD or with amyloid beta levels. However for DS adults with an apoE epsilon4 allele significantly higher serum cholesterol levels were found. CONCLUSION: Hypercholesterolaemia is not a risk factor for DAD in persons with DS. However, DS persons with an apoE epsilon4 allele are susceptible to high serum cholesterol. Such individuals should be screened on a regular basis.

Review of donepezil, rivastigmine, galantamine and memantine for the treatment of dementia in Alzheimer's disease in adults with Down syndrome: implications for the intellectual disability population.

The management of dementia in Alzheimer's disease has dramatically changed since the development of anti-dementia drugs. However, there is limited information available regarding the bio-medical aspects of the differing drugs; particularly relating to adults with intellectual disability. Indeed the information available for the intellectual disabled population is limited to adults with Down syndrome. This review highlights the important pharmacological and clinical aspects of donepezil, rivastigmine, galantamine and memantine and supports the view that such drugs play an important part in the management of dementia in adults with intellectual disability. Future clinical and research issues are discussed.

Weight loss in adults with Down syndrome and with dementia in Alzheimer's disease.

An association between weight loss and Alzheimer's disease has been established in the general population but little information is available regarding this association in people with intellectual disabilities. A 4-year longitudinal study of adults with Down syndrome with and without Alzheimer's disease was undertaken. Age-associated weight loss was seen in virtually all older adults with Down syndrome. A significant association between weight loss and Alzheimer's disease was found for older adults with Down syndrome. This study highlights important research and clinical issues regarding weight loss and nutrition in Down syndrome adults with dementia.

Down syndrome and thyroid disorders: a review.

Thyroid disorders are common in the Down syndrome population but many specific areas of importance remain to be resolved. A detailed review of previously published case reports and research studies highlighting the clinical association between Down syndrome and thyroid disorders was undertaken. Historical, epidemiological, immunological, diagnostic and treatment issues are addressed. Recommendations for future management and research are considered.

Maladaptive behaviours and symptoms of dementia in adults with Down's syndrome compared with adults with intellectual disability of other aetiologies.

Dementia commonly occurs in elderly people with intellectual disability, especially those with Down's syndrome. The non-cognitive symptoms of dementia can be of greater significance to individuals and carers than the cognitive changes caused by this condition. It is not known whether there are differences between people with Down's syndrome and those with intellectual disability of other causes with regard to the prevalence of such symptoms. The present study was undertaken to draw a comparison between a group with Down's syndrome and dementia (n = 19), and a group with intellectual disability of other causes and dementia (n = 26). Maladaptive behaviours and psychiatric symptomatology were assessed in both groups. The group with Down's syndrome had a higher prevalence of low mood, restlessness/excessive overactivity, disturbed sleep, being excessively uncooperative and auditory hallucinations. Aggression occurred with greater frequency in those subjects with intellectual disability of other causes. These findings are of epidemiological importance in terms of service planning and understanding psychiatric presentation.

Longitudinal changes in adaptive behavior in adults with Down syndrome: interim findings from a longitudinal study.

Age-related changes in adaptive behavior have been established in adults with Down syndrome. However, most studies have been cross-sectional, without controls for cohort and survival effects. We examined underlying factors for age-related decline in adaptive behavior in 128 adults with trisomy 21 over a 3-year period. Presence of dementia was the only determining factor, although the difference in trend over time as compared to subjects without dementia was not significant. No association between gender, sensory loss, severity of mental retardation, or place of residence was found. For subjects with no significant medical disorder (physical or psychological), no decline was seen. This longitudinal study confirms previously reported findings.

Molecular mapping of Alzheimer-type dementia in Down's syndrome.

Previous research has hypothesized an association between Alzheimer's disease and the amyloid precursor protein (APP) gene found on chromosome 21. We report the case of a 78-year-old woman with Down's syndrome with partial trisomy 21 [46,XX,rec(21)dup q, inv(21) (p12q22.1)]. No evidence of Alzheimer's disease was found on neuropsychological, magnetic resonance imaging, and neuropathological assessment. The gene sequence for APP was present in only two copies. This case further supports the hypothesis that Alzheimer's disease is associated with trisomy for proximal chromosome 21q, including the APP gene.

ApoE genotype and Alzheimer's disease in adults with Down syndrome: meta-analysis.

The apoE gene polymorphism was examined in 100 adults with Down syndrome (with and without dementia) compared to 346 control subjects without mental retardation. Meta-analysis of available data (480 subjects) revealed that apolipoprotein E genotype distribution for people with Down syndrome was similar to that of the nonretarded population. Although no significant association between possession of the apoE epsilon 4 allele and onset of Alzheimer's disease was found, subjects with the allele had a tendency towards lower age of onset of dementia. Subjects with apoE epsilon 2 allele may not develop dementia and may have increased longevity.