Objective Impairments associated with attention-deficit/hyperactivity disorder (ADHD) and noncompliance are prevalent in children with autism spectrum disorder (ASD). However, ADHD response to stimulants is well below rates in typically developing children, with frequent side effects. Group studies of treatments for noncompliance are rare in ASD. We examined individual and combined-effectiveness of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance. Method In a 3-site, 10-week, double-blind, 2×2 trial of ATX and PT, 128 children (ages 5–14) with ASD and ADHD symptoms were randomized to ATX, ATX+PT, placebo+PT, or placebo. ATX was adjusted to optimal dose (capped at 1.8 mg/kg/day) over 6 weeks and maintained for 4 additional weeks. Nine PT sessions were provided. Primary outcome measures were the parent-rated DSM ADHD symptoms on the Swanson, Nolan and Pelham (SNAP) scale and Home Situations Questionnaire (HSQ). Results On the SNAP, ATX, ATX+PT and placebo+PT were each superior to placebo (effect sizes 0.57–0.98), with p-values of 0.0005, 0.0004 and 0.025, respectively. For noncompliance, ATX and ATX+PT were superior to placebo (effect sizes 0.47–0.64; p values of .03 and .0028, respectively). ATX was associated with decreased appetite but otherwise well-tolerated. Conclusion Both ATX and PT resulted in significant improvement on ADHD symptoms while ATX (both alone and combined with PT) was associated with significant decreases on measures of noncompliance. ATX appears to have a better side effects profile than psychostimulants in the population with ASD.

Introduction In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology. Methods PET imaging with [11C]PiB examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellum as the reference region. Results Multiple linear regression revealed slight but highly significant (corrected p<0.05) positive correlations between SUVR and age. The striatum showed the strongest correlation, followed by precuneus, parietal cortex, anterior cingulate, frontal cortex, and temporal cortex. Conclusion There is an age-related amyloid-β deposition in the DS population, but as a pattern of elevated cortical retention becomes apparent, the correlation of SUVR with age ceases to be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.

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IntroductionDown syndrome (DS) arises from a triplication of chromosome 21, causing overproduction of the amyloid precursor protein and predisposes individuals to early Alzheimer's disease (AD).MethodsFifty-two nondemented adults with DS underwent two cycles of carbon 11-labeled Pittsburgh compound B ([11C]PiB) and T1 weighted magnetic resonance imaging (MRI) scans 3.0 ± 0.6 years apart. Standard uptake value ratio (SUVR) images (50–70 minutes; cerebellar gray matter [GM]) and GM volumes were analyzed in standardized space (Montreal Neurological Institute space).Results85% of PiB(−) subjects remained PiB(−), whereas 15% converted to PiB(+), predominantly in the striatum. None reverted from PiB(+) to PiB(−). Increases in SUVR were distributed globally, but there were no decreases in GM volume. The PiB positivity groups differed in the percent rate of change in SUVR [PiB(−): 0.5%/year, PiB converters: 4.9%/year, and PiB(+): 3.7%/year], but not in GM volume.DiscussionDespite the characteristic striatum-first pattern, the global rate of amyloid accumulation differs by pre-existing amyloid burden and precedes atrophy or dementia in the DS population, similar to general AD progression.