Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. The United States Preventive Service Task Force (USPSTF) has developed criteria for prioritizing conditions of public health importance with the potential for providing screening recommendations to improve clinical care. The quality of existing evidence needed to inform clinical guidelines has not been previously reviewed. Using the National Library of Medicine (NLM) database PubMed, we first identified 18 peer reviewed articles that addressed co-occurring medical conditions in adults with DS. Those conditions discussed in over half of the articles were prioritized for further review. Second, we performed detailed literature searches on these specific conditions. To inform the search strategy and review process a series of key questions were formulated a priori. The quality of available evidence was then graded and knowledge gaps were identified. The number of participating adults and the design of clinical studies varied by condition and were often inadequate for answering all of our key questions. We provide data on thyroid disease, cervical spine disease, hearing impairment, overweight-obesity, sleep apnea, congenital heart disease, and osteopenia-osteoporosis. Minimal evidence demonstrates massive gaps in our clinical knowledge that compromises clinical decision-making and management of these medically complex individuals. The development of evidence-based clinical guidance will require an expanded clinical knowledge-base in order to move forward.

Down syndrome (DS) is one of the most common causes of intellectual disability. Although DS accounts for only 15% of all individuals with intellectual disabilities, adults with DS account for approximately 60% of individuals with intellectual disabilities and Alzheimer’s disease. This is thought to be because of overproduction of the β-amyloid (Aβ) protein due to trisomy for the Aβ precursor protein gene on chromosome 21. Pittsburgh compound B (PiB) is a noninvasive in vivo positron emission tomography tracer used to image amyloid deposition in living humans. Studies using PiB have shown an age-dependent asymptomatic amyloid deposition in more than 20% of the cognitively normal elderly population. Presymptomatic carriers of presenilin (PS-1) and Aβ precursor protein gene mutations who are destined to develop Alzheimer’s disease also show preclinical amyloid deposition. This report describes a pilot study involving the use of PiB in seven adults with DS (age: 20–44 years). Compared with objective cutoffs for amyloid positivity in older non-DS cognitively normal control subjects, only two of the seven DS subjects (age: 38 and 44 years) showed increased PiB retention. The remaining five subjects aged between 20 and 35 years showed no detectable increase in PiB retention. Interestingly, the two subjects who showed elevated PiB retention showed a striatal-predominant pattern similar to that previously reported for PS-1 mutation carriers. These results demonstrate the feasibility of conducting PiB positron emission tomography scanning in this special population, and suggest a link between Aβ overproduction and early striatal deposition of fibrillar Aβ.

; for the Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup IMPORTANCE Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. OBJECTIVE To develop an evidence-based clinical practice guideline for adults with Down syndrome. EVIDENCE REVIEW The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE,

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.

Adults with Down syndrome (DS) have a high incidence of Alzheimer’s disease (AD), providing a unique opportunity to explore the early, preclinical stages of AD neuropathology. We examined change in brain amyloid-β accumulation via the PET tracer [11C] Pittsburgh compound B (PiB) across two data collection cycles, spaced 3 years apart, and decline in cognitive functioning in 58 adults with DS without clinical AD. PiB retention increased in the anterior cingulate gyrus, precuneus cortex, parietal cortex and anterior ventral striatum. Across the two cycles, 14 (27.5%) participants were consistently PiB+, 31 (60.8%) were consistently PiB−, and 6 (11.7%) converted from PiB− at Cycle 1 to PiB+ at Cycle 2. Increased global amyloid-β was related to decline in verbal episodic memory, visual episodic memory, executive functioning, and fine motor processing speed. Participants who were consistently PiB+ demonstrated worsening of episodic memory, whereas participants who were consistently PiB− evidenced stable or improved performance. Amyloid-β accumulation may be a contributor to or biomarker of declining cognitive functioning in preclinical AD in DS.

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.

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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.Correspondence concerning this article should be addressed to Iulia Mihaila, University of Wisconsin -Madison, Waisman Center, 1500 Highland Ave, Madison, WI 53705 (mihaila@wisc.edu). (Zigman & Lott, 2007). Individuals with DS experience "accelerated aging" (e.g., Horvath et al., 2015;Moran, 2013;Patterson & Cabelof, 2012), and have a current life expectancy of about 60 years (Torr, Strydom, Patti, & Jokinen, 2010;Zigman & Lott, 2007). Little research has examined the daily lives of middle-aged and older adults with DS, and even less is known about their leisure activity, defined as pleasurable activities outside of the demands of work. Participation in leisure activity is a strong determinant of psychological well-being in middle-aged and older adults in the general population (e.g., Brajša-Žganec, Merkaš, & Šverko, 2011, Pressman et al., 2009, and in adolescents and young adults with intellectual and developmental disabilities (IDD; e.g., Badia, Orgaz, Verdugo, Ullán, & Martinez, 2011;García-Villamisar & Dattilo, 2010). Unfortunately, evidence suggests that middle-aged and older adults with DS may be at risk for low leisure activity participation. In part, the "accelerated aging" of adults with DS (i.e., early onset of neuropathological, medical, and functional features of aging) may limit leisure activity opportunities. Additionally, there are fewer formal disability support services for middle-aged and older adults with DS, as compared to services for individuals with DS at earlier life stages, and these services generally do not promote leisure activity (Browder & Cooper, 1994;Pruchno & McMullen, 2004). Given the lack of structured leisure activity support services, leisure activity participation may be reliant on the involvement of primary caregivers. The purpose of the present study was to evaluate the leisure activity of 62 middle-aged and older adults with DS (aged 30-53 years) and its association with caregiver involvement (i.e., residence and time spent with primary caregiver). HHS Public AccessLeisure activities are not equally beneficial in terms of promoting psychological well-being.Research on the general population i...