The clinical and neurobehavioral course of Down syndrome and dementia with or without new-onset epilepsy

BackgroundAdult patients with Down syndrome (DS) are at higher risk of developing Alzheimer-type dementia and epilepsy. The relationship between developing dementia and the risk of developing seizures in DS is poorly characterized to date. In addition, treatment response and medication tolerability have not been rigorously studied.MethodsWe identified 220 patients with a diagnosis of DS and dementia. Those without a history of developing seizures (DD) were compared to patients with new-onset seizures (DD + S) after the age of 35. Electronic records were reviewed for demographics, seizure characteristics, cognitive status, and psychiatric comorbidities.ResultsOf the patients included for analysis, twenty-six out of 60 patients had new-onset seizures or developed seizures during the follow-up period (the DD + S group) with a median onset of 2.0 years after the dementia diagnosis. Generalized tonic–clonic seizures were the most common seizure type (61.5% of DD + S). Sixteen (61.5%) patients were reported to have myoclonus. Levetiracetam was the most commonly used initial medication, with the majority (73%) of patients treated achieving partial or complete seizure control. The DD + S patients tended to have a similar burden of new-onset neuropsychiatric symptoms compared to the DD group.DiscussionNew-onset epilepsy seems to occur early in the course of dementia in DS patients. Patients generally respond to treatment. A great burden of neuropsychiatric symptoms is seen. Future studies need to explore the relationship between β-amyloid accumulation and epileptiform activity and attend to the care and needs of DS patients with dementia and seizures.     

MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia

OBJECTIVE: This study sought to determine whether volumes of the hippocampus and amygdala are disproportionately smaller in subjects with Down's syndrome than in normal comparison subjects and whether volume reduction is greater in Down's syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's syndrome (eight with dementia) and 25 cognitively normal adults who were individually matched on age, sex, and race. Magnetic resonance imaging measures included volumes of the hippocampus, amygdala, and total brain. Nineteen of the Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months). RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes of the hippocampus, but not the amygdala, than their comparison subjects, even when total brain volume was controlled for. Volumes of both the hippocampus and the amygdala were smaller in the demented Down's syndrome subjects than in their comparison subjects, even when total brain volume was controlled for. Age was not correlated with volume of the hippocampus or amygdala among the nondemented Down's syndrome subjects and the comparison subjects; age was correlated with volume of the amygdala, but not the hippocampus, among the Down's syndrome subjects with dementia. Changes in volume over time were not statistically significant for either the demented or the nondemented subjects. CONCLUSIONS: Hippocampal volume, while disproportionately small for brain size in individuals with Down's syndrome, remains fairly constant through the fifth decade of life in those without dementia. All subjects over age 50 who had Down's syndrome demonstrated volume reduction in the hippocampus as well as clinical signs of dementia. Dementia was also associated with volume reductions in the amygdala that exceeded reductions in total brain volume.     

Work stress and people with Down syndrome and dementia

This study aimed to assess how staff ratings of challenging behaviour for people with Down syndrome and dementia affected the self-reported well-being of care staff. Data were collected from 60 care staff in 5 day centres in a large city in England. The data were collected by use of a questionnaire. There was no significant difference between those who cared for individuals with Down syndrome and dementia and those caring for service users with other non-specified learning disabilities without dementia, regarding their self-reported well-being. Self-reported well-being did correlate with staff rating of challenging behaviour in both those who cared for people with Down syndrome and dementia and those who did not care for such service users, with well-being declining as perceived challenging behaviour increased. The findings indicate that challenging behaviour prevention and reduction may be of benefit to both service users and care staff well-being.     

Progressive myoclonus epilepsy in Down syndrome patients with dementia

This study aimed to elucidate the natural history of senile myoclonic epilepsy, a type of myoclonic epilepsy associated with Alzheimer’s disease in adult Down syndrome patients. Twelve Down syndrome patients over the age of 40 years with myoclonic epilepsy and Alzheimer’s disease underwent clinical, neuropsychological, neurophysiological, and neuroradiological study. The kariotypes, APOE polymorphisms, all exons in the PSEN1 and PSEN2 genes, and exons 16 and 17 in the APP gene were determined for all patients. CSF Aβ42, p-tau₁₈₁, and t-tauAg were determined for two patients. Three main stages appeared during the course of the syndrome. The first stage was characterized by dementia onset (mean age: 51 ± 6.6 years), diffuse EEG abnormalities during sleep, and cerebral atrophy determined using neuroimaging. During the second stage, myoclonic epilepsy manifested (mean age: 51.4 ± 7.2 years) with myoclonic jerks time-locked to diffuse epileptiform abnormalities upon awakening, which was controlled with antiepileptic drugs. During the third stage (mean age: 54.8 ± 7.6 years), myoclonic seizures were replaced with nonepileptic myoclonus, and cerebellar signs, severe dementia, and photosensitivity developed. All patients showed complete trisomy 21. Mutations were ruled out on the APP, PSEN1, and PSEN2 genes, and APOE analysis revealed ε3/ε3 homozygosity. CSF biomarkers showed a decrease in Aβ42 and an increase in p-tau₁₈₁. The natural history of senile myoclonic epilepsy is consistent with progressive myoclonus epilepsy. Chromosome 21 is implicated in its pathophysiology; however, other genetic and/or environmental risk factors cannot be excluded. The absence of the APOE type 4 allele could predict its progression.     

Dendrites, dementia and the Down syndrome

Findings from a Golgi study of the visual cortex in patients with the Down syndrome were compared with those from neurologically normal, age-matched control subjects. The dendritic atrophy seen in childhood continued into adulthood, with a marked decrease in dendritic branching, dendritic length, and spine frequency in elderly adults with the Down syndrome. Subject more than 30 years old occasionally had degenerating pyramidal neurons in the cerebral cortex and degenerated pyramidal neurons and aspiny stellate cells, particularly in the temporal cortex. These dendritic abnormalities may be related to mental retardation in children and early dementia in older adults who have the Down syndrome. The genetic and extrinsic factors may be important determinants of Alzheimer type dementia in the Down syndrome.     

Gait development during lifespan in subjects with Down syndrome

In this work we studied and evaluated the effects of aging in a group of individuals with Down syndrome, using gait analysis as tool of investigation.32 individuals suffering from Down syndrome (DS) were enrolled in this study as group of pathological participants. The control group (CG) was composed by 36 healthy subjects (10 children, 15 teenagers and 16 adults) in order to evidence the differences between the normal and the pathological gait evolution in age-matched comparisons.The assessment consisted of 3D gait analysis: all pathological participants performed gait analysis in a longitudinal examination, from childhood to adulthood.Participants with DS evidenced how the delay in cognitive aspects and the typical orthopedic features of DS, as ligament laxity, led to the development of different motor strategies. During childhood, for both the considered populations, we found large variability in the gait indexes, but after this age a split in gait development was evidenced: the participants with DS developed a strategy focused on the reduction of the degrees of freedom, increasing the dispersion of generated power in the frontal plane, while in healthy participants the strategy was focused on the use of all the degrees of freedom, in order to reach the effectiveness of the gesture and finalize their movements in sagittal progression.The present study reinforces the idea that early intervention aimed to improve muscle tone, in order to supply for the excessive ligament laxity and to improve motor coordination, could represent a real goal for a more effective movement and for the prevention of compensatory strategies that increase energy cost.     

Health co-morbidities in ageing persons with Down syndrome and Alzheimer's dementia

Background Consideration of the relationship between physical and mental health co-morbidities in ageing persons with Down syndrome (DS) and Alzheimer's dementia (AD) is of clinical importance both from a care and resource perspective. Aim To investigate and measure health co-morbidities in ageing persons with Down syndrome with and without AD. Methods Recorded physical and mental health needs were ascertained for 124 persons with DS > 35 years through a systematic and detailed search of individual medical and nursing case records. Differences in persons with and without AD were investigated, by stage of dementia and by level of intellectual disability (ID). A summed score for health co-morbidities was created and compared using t-tests. Results Persons with AD had significantly higher co-morbidity scores than persons without AD (t = −8.992, d.f. = 121, P < 0.0001). There was also a significant difference in summed co-morbidity scores for persons at end-stage vs. persons at mid-stage AD (t = −6.429, d.f. = 56, P < 0.0001). No differences were found by level of ID. Conclusions Increasing health co-morbidities in persons with DS and AD have important implications for care and resources. Appropriate environmental supports combined with competent skilled staff are crucial and will have an important impact on the quality of life for this increasingly at risk population.     

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.     

Physical activity patterns in children with and without Down syndrome

Summary

PURPOSE: To describe physical activity (PA) patterns in children with Down syndrome (DS) compared to their unaffected siblings. METHODS: Children with DS (n = 28) and their siblings (n = 30), between 3-10-years (mean +/- SD 7.1 +/- 2.1 years) participated in a nutrition and growth study. PA was measured over 7 days using accelerometers. RESULTS: Children with DS were younger (6.6 vs. 7.1 years) and heavier (BMI 18.4 vs. 16.7 kg m(-2)) than their siblings (p < 0.05). Overall, participants accumulated 2.5 hours per day in moderate- (MPA) and 59 min per day in vigorous-intensity activity (VPA), consistent with the current PA recommendations for children. Children with DS accumulated less VPA than their siblings (49.5 vs. 68.6 minutes per day; p = 0.04) and for shorter bouts (2.5 vs. 5.1 minutes per bout; p < 0.01), but spent similar time in MPA and low-intensity PA. Analyses adjusted for age, sex, race, ethnicity, income, maternal education and BMI showed similar results. CONCLUSIONS: Children with DS participated in less total and sustained VPA and had higher BMI levels compared with their siblings. Because children with DS have a tendency toward childhood obesity, increasing participation in VPA may be appropriate for prevention of obesity and promotion of lifelong health.     

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.     

Longitudinal changes in brain CT scans and development of dementia in Down's syndrome

To determine the relationship of the development of dementia to longitudinal changes in brain CT scans in patients with Down's syndrome (DS), we studied 14 Japanese DS patients at an interval of 10 years. The age at entry to the study was 35.7 +/- 9.9 (mean +/- SD) years in 1989 when we did the first CT scans. We performed the second CT scans in 1999 and quantitatively compared them with those taken in 1989. The 4 oldest of the patients (the demented group, 55.3 +/- 1.4 years of age in 1999) developed symptoms of cognitive decline before 1999. The younger 10 (the non-demented group, 41.9 +/- 9.0 years of age in 1999) remained stable in cognitive function until 1999. Despite the clear difference between the demented and the non-demented group in brain atrophy in 1999, CT measures of the demented group were similar to those of the non-demented group in 1989. These results indicate that age is a better predictor of dementia than imaging studies and that CT does not show a quantitative difference between the demented and the non-demented group before the onset of dementia.     

Quantified electroencephalographic changes in Parkinson's disease with and without dementia

We examined the presence of quantified electroencephalographic (qEEG) differences between Parkinson's disease (PD) patients with and without dementia, and a group of age-comparable normal controls. While there were no significant differences in relative power in any of the qEEG bands between PD patients without dementia and normal controls, PD patients showed a significantly greater reactivity in the alpha band. On the other hand, PD patients with dementia showed significantly less alpha and more theta relative power than both the normal control and the PD without dementia groups. When PD patients with dementia were compared with a group of patients with Alzheimer's disease (AD) and a similar severity of dementia, no significant between-group differences were found in any of the qEEG bands. In conclusion, while our study demonstrated no significant qEEG differences between non-demented PD patients and normal controls, PD patients with dementia showed qEEG changes similar to those observed in patients with AD.     

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.     

Behavioural characteristics associated with dementia assessment referrals in adults with Down syndrome

Background Behavioural changes associated with dementia in Down syndrome are well documented, yet little is known about the effect of such behaviours on carers and referral. By comparing the behavioural and cognitive profiles of individuals referred for a dementia assessment with those of individuals not referred, some insight can be gained into behavioural characteristics that initiate referral for specialist support or interventions. Method Forty‐six adults with Down syndrome were divided into two groups dependent upon method of entry into the study; post‐referral to a specialist service for older adults with intellectual disabilities and Down syndrome for a dementia assessment (n = 17) or after receiving information sent out to day centres and residential homes (n = 29). These groups were compared on established measures of dementia alongside two informant measures of behaviour. Results Those referred for a dementia assessment evidenced scores indicative of cognitive decline on both informant and direct Neuropsychological Assessments and showed more behavioural excesses, but not deficits, and lower socialisation and coping skills than those in the comparison group. Carers of those referred for a dementia assessment reported a greater impact of behavioural excesses on staff than on the individual showing the behaviour in contrast to the comparison group. Conclusion The behavioural differences between those referred and the comparison group suggest that two factors are involved in the instigation of a referral for a dementia assessment: the nature of the behavioural presentation (excesses rather than deficits) and the effect of that behavioural change upon the care staff.     

Cerebral changes in SLE with or without antiphospholipid syndrome. a case-control MRI study

BACKGROUND: To determine and characterize the prevalence of cerebral changes on MRI in patients with antiphospholipid syndrome (APLS) within systemic lupus erythematosus (SLE). METHODS: Seventy-one patients with SLE were prospectively studied with brain MRI: 32 with definite APLS and 39 without. Atrophy, ventricular enlargement, leukoaraiosis, interuncal distance, Evans' index, infarcts, and white matter hyperintensities (WMH) were analyzed. Demographic data, treatment, and SLE activity were analyzed. RESULTS: Groups were similar in age (32.4 vs. 32.8 years old; P= non-significant [NS]), and gender. Duration of disease was longer in patients with APLS (87.3 vs. 55.4 months; P= .064). Cortical atrophy was common in both groups (68.7% vs. 89.7%; P= NS). Leukoaraiosis was present in only 3 patients (9.4%; P= .08), all in the APLS group. WMH were found in more than 40% of the patients from both groups. Infarcts (21.9% vs. 2.6%; P= .019) and infarcts plus WHM (12.5% vs. 0; P= .037) were more common in patients with APLS. CONCLUSIONS: Although a higher prevalence of neurological involvement in SLE has been reported in APLS patients, we found gross brain changes to be similar between groups. Strokes and leukoaraiosis were more common in the APLS group, consistent with the idea of an APLS-induced prothrombotic state.     

Brain monoamines in cases with Down's syndrome with and without dementia

Summary Three cases of Down's syndrome, one of which had a clinical history of a presenile dementia during final years, were analyzed for the content of tyrosine (Tyr), dopamine (DA), noradrenaline (NA), tryptophan (Try), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the following regions: the caudate nucleus, the putamen, the thalamus, the mesencephalon, and the hippocampus. A rather generalized reduction of DA, NA, 5-HT, and 5-HIAA was noted in the demented DS case.