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.     

Reliability of diagnosing clinical hypothyroidism in adults with Down syndrome

Although thyroid dysfunction is associated with Down syndrome, the clinical manifestation of the dysfunction has not been fully researched. This study investigated the accuracy of diagnosing hypothyroidism in 160 adults with Down syndrome on clinical findings alone. A significant association between a clinical diagnosis of hypothyroidism and increasing age was found but no significant association was found between a clinical and a biochemical diagnosis. Regular biochemical screening for thyroid dysfunction in people with Down syndrome is recommended.     

A comparison between older persons with down syndrome and a control group: clinical characteristics, functional status and sensorimotor function

The increase in life expectancy within the general population has resulted in an increasing number of elderly adults with intellectual disability, and this is reflected in the increased life expectancy in persons with Down syndrome, currently about 56 years. The aim of this study was to study the clinical characteristics, the functional status and sensori-motor function of 10 older persons with Down syndrome (mean age 59 years), 13 younger persons with Down syndrome (mean age 44 years) and compare them with 38 adults with intellectual disability without Down syndrome and a control group of people without intellectual disability. All the persons with Down syndrome and intellectual disability resided in two residential living centres in Israel, while the 31 older persons without intellectual disability (mean age 75 years), who served as the control group, lived in an independent living facility. The study considered demographic data, medical backgrounds, physical and functional tests. The results showed that the older persons with Down syndrome in the study were more obese, shorter and had more medical problems than both the older persons with intellectual disability and the control group. The functional performance of the older adults with Down syndrome was more impaired in comparison with both other groups. It is postulated that their slower responses may be explained by a less physically active lifestyle, that may accelerate the onset of disease, resulting in symptoms associated with aging that are detrimental to health.     

Age-specific prevalence,thyroid dysfunction and depressive symptomatology in adults with down syndrome and dementia

Two hundred and one adults with Down syndrome (DS) were investigated for differing aspects of clinical dementia. Age-specific prevalence rates of 9.4% for age range 40–49 years, 36.1% for 50–59 years and 54.5% for 60–69 years were found. Findings associated with increasing severity of dementia were gait deterioration, onset of urinary incontinence, increased muscle tone and onset of seizures. No association was found between thyroid dysfunction or thyroid autoimmunity and dementia. However, depressive symptomatology of depressed mood, weight loss and reduced appetite were associated with dementia. These findings investigating Alzheimer's disease (AD) in adults with DS support findings reported for the non-learning disability population of an association between age, depressive symptomatology and AD but no association between thyroid dysfunction and AD.     

End-stae dementia in adults with down syndrome

End-stage dementia in adults with Down syndrome has not been fully investigated. Available information, 6 months prior to death, for 20 adults with Down syndrome who had died with Alzheimer's disease was reviewed. A terminal stage of severe intellectual deterioration, marked personality and mood changes, loss of sphincter control, seizure activity, immobility with hypertonia and complete loss of self-care skills was found. These findings have important clinical and service implications.     

Repetition priming in adults with Williams syndrome: age-related dissociation between implicit and explicit memory

We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down syndrome and those with unspecified mental retardation. A similar dissociation was observed in adults with Down syndrome but not in adults with unspecified mental retardation. An IQ-related dissociation was also found. Implicit and explicit memory, therefore, show different degrees of association with age and IQ, supporting theories of these memory processes. Results also suggest that Williams syndrome, similar to Down syndrome, may be associated with precocious aging, resulting in the loss of some cognitive abilities.     

Selective attention deficits associated with mild cognitive impairment and early stage Alzheimer's disease in adults with Down syndrome

Adults with Down syndrome and early stage Alzheimer's disease showed decline in their ability to selectively attend to stimuli in a multitrial cancellation task. They also showed variability in their performance over the test trials, whereas healthy participants showed stability. These changes in performance were observed approximately 2 years prior to a physician's diagnosis of possible Alzheimer's disease, which was made when they were exhibiting declines in episodic memory suggestive of mild cognitive impairment. Performance on this task varied with the evolution of dementia, showed modestly good sensitivity and specificity, and was relatively easy to administer. Given these qualities this task could be a valuable addition to a neuropsychological battery intended for the assessment of mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.     

Disease-specific patterns of locus coeruleus cell loss.

Computer visualization techniques were used to map and to quantitatively reconstruct the entire locus coeruleus, including the nucleus subcoeruleus, to compare the topographic patterns of cell loss in postmortem brains from patients with Parkinson's disease, Alzheimer's disease, and Down syndrome. There was comparable cell loss in all three diseases (approximately 60%) compared with aged normal subjects, and there was a significant loss of nucleus subcoeruleus cells specifically in patients with Parkinson's disease (63%). There was a significant positive correlation between the magnitude of locus coeruleus cell loss and the duration of Alzheimer's disease, but no such correlation was found for Parkinson's disease. In patients with Parkinson's disease, there was comparable cell loss throughout the rostral-caudal extent of the nucleus; however, in patients with Alzheimer's disease and Down syndrome, the greatest cell loss always occurred within the rostral portion of the nucleus, with a relative sparing of caudal cells. These data are consistent with the hypothesis that cell loss in Parkinson's disease is the result of a pathological process that attacks the catecholaminergic cells of the locus coeruleus and the subcoeruleus in general; in Alzheimer's disease and Down syndrome, however, the pathological process only affects the rostral, cortical-projecting locus coeruleus cells and spares the caudal, noncortical-projecting cells.     

The impact of sleep disruption on executive function in Down syndrome

The high prevalence of sleep disorders, particularly obstructive sleep apnea, is well established in children with Down syndrome. However, only a few studies have focused on older children and young adults in this population. Given the presence of sleep disorders and the early emergence of Alzheimer's disease, more work is needed to examine the relationship between sleep and cognition in Down syndrome. Twenty-nine adolescents and young adults with Down syndrome participated in the present study. Parents reported on their sleep difficulties using a well-validated measure of sleep problems in intellectual disabilities. Based on theoretical models linking obstructive sleep apnea to prefrontal cortex dysfunction, we tested components of executive functions that have been shown to be impaired in previous studies of Down syndrome. First, results indicate that participants with Down syndrome with higher body mass index also had increased caregiver reports of sleep apnea symptoms. Individuals with high ratings of sleep disruption also showed greater difficulties with executive function. These results suggest that sleep disruption may place this set of functions at risk in young adults. Future work should examine if this risk may result in earlier onset of dementia or steeper decline with Alzheimer's disease. Further, additional studies are needed to investigate the effect of exercise interventions and weight reduction on sleep disorders in this population.     

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.     

Olfactory function in young adolescents with Down's syndrome.

Decreased ability to smell is present in adults with Down's syndrome, many of whom are known to have brain pathology analogous to that seen in Alzheimer's disease. Because olfactory loss is well documented in Alzheimer's disease, the question arises whether young adolescents with Down's syndrome, who have no clear Alzheimer's disease-like neuropathology, also exhibit olfactory dysfunction. To consider this issue, standardised tests of odour discrimination and identification were administered to 20 young adolescents with Down's syndrome (mean age (SD) 13.89 (1.98) years) and their test scores were compared with 20 mentally retarded and 20 non-mentally retarded control subjects matched to the patients with Down's syndrome on the basis of cognitive ability. No significant differences in olfactory function were found among the three study groups. These findings, along with those from studies of olfactory function in older patients with Down's syndrome, suggest that Down's syndrome related olfactory dysfunction occurs only at ages when Alzheimer's disease-like pathology is present.     

Premature regression of adults with Down syndrome

Adaptive skills of 2,144 individuals with Down syndrome were compared to a similar group of 4,172 developmentally disabled people without Down syndrome. Activities of daily living and cognitive skills were examined across etiology, age group, and level of mental retardation. For individuals with Down syndrome at all levels of retardation, adaptive competence declined with increasing age to a greater extent than for retarded control subjects. Clear age-related deficits associated with Down syndrome were observed only in people older than 50 years of age. Findings support previous evidence of an increased risk for the clinical signs of Alzheimer's disease among people with Down syndrome; however, signs of dementia appeared later in life than would be predicted from available neuropathological data.     

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. Copyright (c) 2008 John Wiley & Sons, Ltd.     

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.     

Demographic characteristics, health conditions, and residential service use in adults with Down syndrome in 25 U.S. states

This study describes service users with Down syndrome (N = 1,199) and a comparative sample with intellectual and developmental disabilities but not Down syndrome (N = 11,182), drawn from National Core Indicator surveys of adult service users in 25 U.S. states. Individuals with Down syndrome were younger than were individuals without Down syndrome. Men with Down syndrome were older than women with Down syndrome, whereas the reverse was true of the individuals without Down syndrome. Most (68%) people with Down syndrome had mild or moderate intellectual disability. The prevalence of vision impairment, hearing impairment, and physical disability increased with age. Adults with Down syndrome were more likely to have Alzheimer's dementia, have a hearing impairment, or be overweight, but they were less likely to have a physical disability than those without Down syndrome. Adults with Down syndrome were less likely to live in institutions or their own home, but they more likely to live in a family member's home. The results of a logistic regression showed that participants were more likely to be reported to be overweight if they had Down syndrome, were female, and were physically inactive, but they were less likely to be reported to be overweight if they were older, had more severe intellectual disability, had cerebral palsy, or were not independently mobile.     

Maladaptive behaviors related to dementia status in adults with Down syndrome

Changes in maladaptive behaviors related to specific stages of dementia were investigated in 251 adults 45 years of age and older with Down syndrome. Findings indicate clear differences in maladaptive behaviors at various stages of dementia. Generally, individuals with no signs or symptoms of dementia displayed fewer and less severe maladaptive behaviors than individuals in the early and mid-stages of dementia. Individuals transitioning into the early stages of dementia from no dementia displayed increased aggression, fearfulness, sadness, sleep problems, social inadequacy, stealing, and general regressive behavior. Thus, new concerns regarding these types of behaviors could be particularly useful in clarifying the dementia status of adults with Down syndrome and developing individualized plans for support.     

beta-Amyloid is associated with reduced cognitive function in healthy older adults

Though elevated beta-amyloid deposition is associated with Alzheimer's disease, recent evidence suggests beta-amyloid is elevated in healthy older adults prior to the onset of Alzheimer's disease. No study has yet investigated whether reduced cognitive function is related to beta-amyloid elevation in healthy older adults. Thirty-five healthy older adults underwent neuropsychological testing and fasting blood draw with subsequent serum beta-amyloid 1-40 level quantification. beta-amyloid was negatively correlated with several aspects of cognition. Findings indicate that beta-amyloid level is associated with cognitive function in healthy older adults in a pattern similar to early Alzheimer's disease. Further work investigating possible mechanisms is needed.     

High brain myo-inositol levels in the predementia phase of Alzheimer's disease in adults with Down's syndrome: a 1H MRS study

OBJECTIVE: An extra portion of chromosome 21 in Down's syndrome leads to a dementia in later life that is phenotypically similar to Alzheimer's disease. Down's syndrome therefore represents a model for studying preclinical stages of Alzheimer's disease. Markers that have been investigated in symptomatic Alzheimer's disease are myoinositol and N-acetyl-aspartate. The authors investigated whether abnormal brain levels of myo-inositol and other metabolites occur in the preclinical stages of Alzheimer's disease associated with Down's syndrome. METHOD: The authors used 1H magnetic resonance spectroscopy (MRS) with external standards to measure absolute brain metabolite concentrations in 19 nondemented adults with Down's syndrome and 17 age- and sex-matched healthy comparison subjects. RESULTS: Concentrations of myoinositol and choline-containing compounds were significantly higher in the occipital and parietal regions of the adults with Down's syndrome than in the comparison subjects. Within the Down's syndrome group, older subjects (42-62 years, N = 11) had higher myo-inositol levels than younger subjects (28-39 years, N = 8). Older subjects in both groups had lower N-acetylaspartate levels than the respective younger subjects, although this old-young difference was not greater in the Down's syndrome group. CONCLUSIONS: The approximately 50% higher level of myo-inositol in Down's syndrome suggests a gene dose effect of the extra chromosome 21, where the human osmoregulatory sodium/myo-inositol cotransporter gene is located. The even higher myoinositol level in older adults with Down's syndrome extends to the predementia phase earlier findings of high myoinositol levels in symptomatic Alzheimer's disease.     

Successful aging in a 70-year-old man with down syndrome: a case study

The authors present a case study of a 70-year-old man with Down syndrome ("Mr. C.") who they followed for 16 years and who does not exhibit declines in cognitive or functional capacities indicative of dementia, despite having well-documented, complete trisomy 21. The authors describe the age-associated changes that occurred over 16 years as well as provide detailed information regarding Mr. C.'s health and genetic status. To further emphasize Mr. C.'s successful aging, the authors compared his longitudinal performance profile with that of 2 peers of comparable level of intellectual functioning: 1 similar-aged man with clinical Alzheimer's disease and a younger man who was healthy. The authors present potential explanations for the phenotypic variability observed in individuals with Down syndrome.     

Obesity in adults with Down syndrome: a case–control study

Background Obesity has a negative impact upon mortality and morbidity. Studies report that obesity is more prevalent in individuals with Down syndrome than individuals with intellectual disabilities (ID) not associated with Down syndrome. However, there have been no studies using a methodology of matched comparison groups and findings from previous studies are contradictory. Methods A detailed method was used to identify all adults with ID in Leicestershire. Individuals were invited to participate in a medical examination – that included measurement of their height and weight, from which body mass index (BMI) was calculated. For each person with Down syndrome, an individual matched for gender, age and accommodation type was identified, from the Leicestershire ID database. Results The data for 247 matched pairs is reported. Women with Down syndrome had lower mean height and weight, but greater mean BMI than the matched pairs. Men with Down syndrome had a lower mean height and weight but there was no statistical difference in BMI compared to the matched pairs. Using World Health Organization categories of BMI, women with Down syndrome were more likely to be overweight or obese than their matched pairs (odds ratio = 2.17). Men with Down syndrome were more likely to be in the overweight category than their matched pairs but were less likely to be obese (odds ratio = 0.85). Conclusions This study demonstrates that, compared to a matched sample, there is a greater prevalence of obesity amongst women with Down syndrome but not men. As the impact on the health of people with Down syndrome of being overweight or obese is uncertain, this is an area that requires further study.