Routinised and compulsive-like behaviours in individuals with Down syndrome.

BACKGROUND: Increased intensities of routinised and compulsive-like behaviours are seen in those with intellectual disabilities and have sometimes been shown to be associated with worries. We used the Childhood Routines Inventory (CRI, Evans et al., 1997) with two samples of children and adults with Down syndrome: (1) to determine whether routinised and compulsive-like behaviours were associated with mental health problems and (2) to determine the factor structure of the CRI. METHOD: Parents or carers completed the CRI for (1) 125 adults with Down syndrome (aged 18-43 years) who had been assessed for mental health problems; worries and fears were also rated by parents/carers and (2) 206 individuals with Down syndrome (aged 4.5-43 years, with verbal mental ages of 2 years and above). RESULTS: (1) People with a psychiatric diagnosis had significantly more worries and fears than those without such a diagnosis, but there was no significant difference in CRI scores. Logistic regression indicated that the fear rating was the only significant predictor of a diagnosis. (2) Exploratory and confirmatory analyses showed a three-factor model (Just right, Repetitive behaviour and Clothes sensitivity) to be the best solution. Those with psychiatric diagnoses had significantly higher ratings on the Repetitive behaviour factor. CONCLUSION: Increased levels of routinised and compulsive-like behaviours were shown by individuals with Down syndrome of all ages, were not associated with mental health problems, but were associated with worries and fears. Factor analysis found three factors, two of which (Just right and Repetitive behaviours), were similar to those identified in typically developing samples. This suggests that the behaviours have similar adaptive functions in individuals with developmental delays.

Fifteen-year follow-up of thyroid status in adults with Down syndrome.

BACKGROUND: The natural history of thyroid function in adults with Down syndrome is relatively unknown with limited long-term follow-up data. METHOD: This study investigated annual thyroid function tests in 200 adults with Down syndrome over a 15-year period. RESULTS: For healthy adults with Down syndrome there is a gradual increase in thyroxine and possible gradual decline in thyroid-stimulating hormone with age. The 15-year incidence for definite hypothyroidism remains low and subclinical hypothyroidism is not a precursor for the onset of definite hypothyroidism. CONCLUSIONS: The incidence of thyroid dysfunction is markedly less than would be expected from prevalence studies. Subclinical hypothyroidism is not necessarily a precursor to definite hypothyroidism. Prevalence studies have overstated the association between thyroid dysfunction and Down syndrome. Routine screening for adults with Down syndrome who are euthyroid can be reduced to every 5 years rather than the 1-2 years, as is the present policy.

Brain anatomy and ageing in non-demented adults with Down's syndrome: an in vivo MRI study.

BACKGROUND: People with Down's syndrome (DS) are at high risk for developing dementia in middle age. The biological basis for this is unknown. It has been proposed that non-demented adults with DS may undergo accelerated brain ageing. METHOD: We used volumetric magnetic resonance imaging (MRI) and manual tracing to compare brain anatomy and ageing in 39 non-demented adults with DS and 42 healthy controls. RESULTS: Individuals with DS had significant differences in brain anatomy. Furthermore, individuals with DS had a significantly greater age-related reduction in volume of frontal, temporal and parietal lobes, and a significantly greater age-related increase in volume of peripheral cerebrospinal fluid (CSF). CONCLUSIONS: Non-demented adults with DS have differences in brain anatomy and 'accelerated' ageing of some brain regions. This may increase their risk for age-related cognitive decline and Alzheimer's disease (AD).

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.

Consensus guidelines into the management of epilepsy in adults with an intellectual disability.

BACKGROUND: Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high-quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process. RESULTS: A Delphi process identified a list of priority areas for the development of evidence-based guidelines. All guidelines were graded and consensus on scoring was achieved across the guideline group. CONCLUSION: There is a dearth of high-quality evidence from well-constructed studies on which to base guidance. However, the development of internationally derived consensus guidelines may further support the management of epilepsy in adults with an intellectual disability.

Alzheimer's disease and Down's syndrome: an in vivo MRI study.

BACKGROUND: Individuals with Down's syndrome (DS) are at high risk of developing Alzheimer's disease (AD). However, few studies have investigated brain anatomy in DS individuals with AD. METHOD: We compared whole brain anatomy, as measured by volumetric magnetic resonance imaging (MRI), in DS individuals with and without AD. We also investigated whether volumetric differences could reliably classify DS individuals according to AD status. We used volumetric MRI and manual tracing to examine regional brain anatomy in 19 DS adults with AD and 39 DS adults without AD. RESULTS: DS individuals with AD had significantly smaller corrected volumes bilaterally of the hippocampus and caudate, and right amygdala and putamen, and a significantly larger corrected volume of left peripheral cerebrospinal fluid (CSF), compared to DS individuals without AD. The volume of the hippocampus and caudate nucleus correctly categorized 92% and 92% respectively of DS individuals without AD, and 75% and 80% respectively of DS individuals with AD. CONCLUSIONS: DS individuals with AD have significant medial temporal and striatal volume reductions, and these may provide markers of clinical AD.

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.

Natural history of thyroid function in adults with Down syndrome--10-year follow-up study.

BACKGROUND: The natural history of thyroid function in adults with Down syndrome (DS) is unknown. METHOD: This study investigated annual thyroid function tests in 200 adults with DS over a 10-year period. RESULTS: Transient and persistent thyroid dysfunction was common. The 5- and 10-year incidence of definite hypothyroidism was 0.9%-1.64% and 13.6%, respectively. Subclinical hypothyroidism was not found to be an early sign for definite hypothyroidism. CONCLUSIONS: Routine screening for adults with DS who are euthyroid can be reduced to every 5 years rather than the present policy of every 1-2 years.

Misdiagnosis of thyroid disorders in down syndrome: time to re-examine the myth?

There is a reported association between thyroid disorders and Down syndrome, but is this association based on valid and reliable research evidence? We evaluated thyroid function test results of 110 healthy adults with Down syndrome to determine biochemical thyroid status. Approximately two thirds were biochemically euthyroid when assessed by standard reference ranges for the general population. We believe that there is a need for revalidation of "normal" thyroid function tests parameters when applied to the Down syndrome population and that persons with Down syndrome are possibly being misdiagnosed and inappropriately treated for a nonexistent medical disorder.

The Adaptive Behaviour Dementia Questionnaire (ABDQ): screening questionnaire for dementia in Alzheimer's disease in adults with Down syndrome.

The diagnosis of dementia in Alzheimer's disease remains at times problematic in adults with intellectual disability. The analysis of 5-year consecutive data developed a researched-based clinical screening tool for dementia in Alzheimer's disease in adults with Down syndrome. The Adaptive Behaviour Dementia Questionnaire (ABDQ) is a 15-item questionnaire, which is used to detect change in adaptive behaviour. The scale has good reliability and validity, with an overall accuracy of 92%. It is the first clinical tool designed specifically to screen for dementia in Alzheimer's disease in adults with Down syndrome.

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.

Magnetic resonance imaging, Down's syndrome and Alzheimer's disease: research and clinical implications.

BACKGROUND: The diagnosis of Alzheimer's disease (AD) remains at times difficult to make using available neuropsychological measures. Neuro-imaging is a relatively new form of detecting the changes associated with dementia. The present study investigated the role of magnetic resonance imaging (MRI) in diagnosing AD in adults with Down's syndrome (DS). METHODS: Subjects with DS and Alzheimer-type dementia were matched to non-demented controls with DS. Magnetic resonance imaging findings (i.e. volumetric and two-dimensional scans) were compared between the two groups in order to show a relationship between the changes of AD and structural MRI abnormalities. RESULTS: Specific structural abnormalities which are seen in non-intellectually disabled subjects with dementia are also found in individuals with both DS and AD. However, such findings cannot be used to diagnose clinical AD with good accuracy in adults with DS. A number of practical issues of patient compliance and over-sedation are demonstrated by the findings. CONCLUSIONS: Magnetic resonance imaging has an important but limited role to play in the management of AD in the population with DS. If intravenous sedation is used, medical support is essential to prevent a serious mishap.