Down syndrome regression disorder: updates and therapeutic advances.

PURPOSE OF REVIEW: Down syndrome regression disorder (DSRD) is a symptom cluster consisting of neuropsychiatric regression without cause. Although knowledge of this condition has accelerated over the last decade, prior studies have been limited by heterogenous nomenclature, diagnostic approaches and therapeutic interventions. This review highlights recent advances in the diagnosis and clinical approach to DSRD and reviews the most up-to-date literature on therapeutic interventions for this condition. RECENT FINDINGS: Several multicentre studies have reported exciting findings on the presence of neurodiagnostic study abnormalities and responses to a variety of therapeutics, including psychotropics (including benzodiazepines), electroconvulsive therapy and immunotherapy. Differential response rates have been observed in the presence and absence of a variety of clinical and diagnostic factors. SUMMARY: Individuals with DSRD are responsive to a variety of psychiatric pharmacotherapy and immunotherapy underscoring this phenotype may have multiple causes. Multidisciplinary care is helpful in the evaluation and management of individuals with this condition.

Alzheimer-Like Pattern of Hypometabolism Emerges with Elevated Amyloid-ß Burden in Down Syndrome.

BACKGROUND: The Down syndrome (DS) population is genetically predisposed to amyloid-ß protein precursor overproduction and Alzheimer's disease (AD). OBJECTIVE: The temporal ordering and spatial association between amyloid-ß, glucose metabolism, and gray matter (GM) volume in the DS population can provide insight into those associations in the more common sporadic AD. METHODS: Twenty-four adults (13 male, 11 female; 39±7 years) with DS underwent [11C]PiB, [18F]FDG, and volumetric MRI scans. Voxel-wise associations between PiB SUVR, FDG SUVR, and GM volume were investigated, with and without individual adjustments for variables of interest. RESULTS: Positive associations of PiB and age were widespread throughout the neocortex and striatum. Negative associations of FDG and age (frontal, parietal, and temporal cortex) and of GM volume and age (frontal and insular cortex) were observed. PiB and FDG were negatively associated in parietal cortex, after adjustment for GM volume. CONCLUSIONS: In adults with DS, early amyloid-ß accumulation in the striatum is divergent from sporadic AD; however, despite the early striatal amyloid-ß, glucose hypometabolism was confined to the typical AD-associated regions, which occurs similarly in autosomal dominant AD. Importantly, the glucose hypometabolism was not explained solely by increased partial volume effect due to GM volume reductions.

Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population.

INTRODUCTION: Down 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). METHODS: Fifty-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). RESULTS: 85% 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. DISCUSSION: Despite 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.

Leisure Activity and Caregiver Involvement in Middle-Aged and Older Adults With Down Syndrome.

The present study examined leisure activity and its association with caregiver involvement (i.e., residence and time spent with primary caregiver) in 62 middle-aged and older adults with Down syndrome (aged 30-53 years). Findings indicated that middle-aged and older adults with Down syndrome frequently participated in social and passive leisure activities, with low participation in physical and mentally stimulating leisure activities. Residence and time spent with primary caregiver were associated with participation in physical leisure activity. The findings suggest a need for support services aimed at increasing opportunities for participating in physical and mentally stimulating leisure activity by middle-aged and older adults with Down syndrome. These support services should partner with primary caregivers in order to best foster participation in physical leisure activity.

The effects of normal aging on amyloid-ß deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B.

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 carbon 11-labeled Pittsburgh compound B examined the pattern of amyloid-ß 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 cerebellar gray matter as the reference region. RESULTS: Multiple linear regression revealed slight but highly significant (corrected P < .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-ß 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.