REM sleep and sleep apnea are associated with language function in Down syndrome children: An analysis of a community sample.

BACKGROUND: The prevalence rate of obstructive sleep apnea (OSA) in the community Down syndrome (DS) children is not clear. Moreover, the impact of OSA and sleep structure on the cognitive function is inconclusive. The present study aimed to investigate 1) the prevalence rate of OSA in the community DS children and 2) the impact of OSA and sleep structure on cognitive performance. METHODS: Thirty DS children aged 6-18 years were recruited and evaluated with the performance of the language domain and sensorimotor domain, combining neuropsychological tests and parent-rated behavior. The outcomes were the age-adjusted scores, of which the lower the score was, the better was the patient's ability. The association of score with OSA and sleep structures was determined by linear regression. To diminish the age-related difference, all analyses were conducted separately for all subjects and 6-12-year-old subjects. RESULTS: The median age was 11.3 years and median Full-Scale Intelligence Quotient (FSIQ) was 44. The prevalence of OSA (apnea-hypopnea index ≥ 1/h) was 80% and 62.5% in all subjects and 6-12-year-old subjects, respectively. For 6-12-year-old subjects, after adjustment for age and FSIQ, both %REM and OSA were associated with lower score of the subtest of language domain, WPPSI-R Vocabulary, while %REM was also associated with lower score of VABS-II Communication - Expressive. In contrary, % slow wave sleep was not associated with any subtest. CONCLUSION: This study identified that OSA may be highly prevalent in community DS children. Among 6-12-year-old DS children, OSA and % REM were associated with their language function.

Composite Scores of Plasma Tau and ß-Amyloids Correlate with Dementia in Down Syndrome.

Dementia frequently occurs in Down syndrome (DS) patients, and early intervention is important in its management. We have previously demonstrated a positive correlation of plasma ß-amyloid Aß42 levels and negative correlations of Aß40 and tau levels with dementia in DS. In this study, we examined more cases and constructed composite scores with both tau and amyloids to correlate with dementia in DS. Plasma Aß42, Aß40, and tau proteins were measured by an immunomagnetic reduction assay in DS patients. Data were randomly and repeatedly split into training and validating sets, and logistic regression was applied to calculate the area under the curve (AUC) for each biomarker. A total of 73 DS patients (among them, 23 had neurodegeneration) and 77 controls were recruited. In DS patients without dementia, plasma Aß40 and tau levels were highly elevated, but Aß42 levels were lower than those of the healthy controls. DS patients with dementia, compared with DS patients with no dementia, had a large decline in Aß40 and tau but a rise in Aß42. For biomarker scores correlating with dementia, Aß40 revealed an AUC of 0.912; the composite score of Aß40 × tau revealed an AUC of 0.953; and a combined composite score of 0.1 for Aß40 × Tau +0.9 Tau × Aß40/Aß42 achieved the highest AUC of 0.965. Therefore, composite biomarker scores including both plasma tau and ß-amyloid levels correlate with dementia in DS better than using individual biomarker scores. The pattern of tau decline and Aß42 rise in DS patients with dementia are also different from previous findings in Alzheimer's disease.

Blood Beta-Amyloid and Tau in Down Syndrome: A Comparison with Alzheimer's Disease.

Background: Changes in ß-amyloids (Aß) and tau proteins have been noted in patients with Alzheimer's disease (AD) and patients with both Down syndrome (DS) and AD. However, reports of changes in the early stage of regression, such as behavioral and psychological symptoms of dementia (BPSD), in DS are sparse. Methods: Seventy-eight controls, 62 patients with AD, 35 with DS and 16 with DS with degeneration (DS_D), including 9 with BPSD and 7 with dementia, were enrolled. The levels of ß-amyloids 40 and 42 (Aß-40, Aß-42) and tau protein in the blood were analyzed using immunomagnetic reduction (IMR). The Adaptive Behavior Dementia Questionnaire (ABDQ) was used to evaluate the clinical status of the degeneration. Results: The Aß-40 and tau levels were higher and the Aß-42 level and Aß-42/Aß-40 ratio were lower in DS than in the controls (all p < 0.001). Decreased Aß-40 and increased Aß-42 levels and Aß-42/40 ratios were observed in DS_D compared with DS without degeneration (all p < 0.001). The ABDQ score was negatively correlated with the Aß-40 level (ρ = -0.556) and the tau protein level (ρ = -0.410) and positively associated with the Aß-42 level (ρ = 0.621) and the Aß-42/40 ratio (ρ = 0.544; all p < 0.05). Conclusions: The Aß-40 and Aß-42 levels and the Aß-42/Aß-40 ratio are considered possible biomarkers for the early detection of degeneration in DS. The elevated Aß-40 and tau levels in DS may indicate early neurodegeneration. The increased Aß-42 in DS_D may reflect the neurotoxicity of Aß-42. The paradox of the tau decreases in DS_D could be explained by a burnout phenomenon during long-term neurodegeneration. The different patterns of the plasma beta amyloids and tau protein may imply a different pathogenesis between DS with degeneration and AD in the general population, in spite of their common key pathological features.

Promising outcomes in glutaric aciduria type I patients detected by newborn screening.

Glutaric aciduria type I (GA-I) is an inborn error of lysine and tryptophan metabolism. Clinical manifestations of GA-I include dystonic or dyskinetic cerebral palsy, but when the symptoms occur, treatment is not effective. In Taiwan, newborn screening for GA-I started in 2001; we wish to evaluate the outcomes of patients detected through newborn screening. Newborns diagnosed with GA-I by abnormal dried blood spot glutarylcarnitine (C5DC) levels followed in our hospital were included in this study. They were treated with special diets, carnitine supplements, and immediate stress avoidance. Six patients were included in this study. All patients were treated prior to reaching 1 month of age. They were followed up with for 4 to 9 years. One patient had encephalopathic crisis episodes prior to turning 1 year old that caused pallidal lesions. Another patient had a chronic progressive disease during infancy that caused bilateral putamen lesions. These two patients had delayed development, but their brain lesions were resolved. The other four patients ran uneventful courses. They had normal intelligenece, ranged between average to low average level and their brain magnetic resonance imaging showed only high intensity over deep white matter. Patients with GA-I diagnosed by newborn screening have promising outcomes, though the risks of disease progression prior to 1 year of age remain significant.