A Scoping Review of Animal-Assisted Interventions for Individuals With Down Syndrome

The goal was to investigate the prevalence of renal and urinary tract anomalies (RUTAs) in a Down syndrome (DS) population. Data were obtained from the New York State Congenital Malformation Registry (NYS-CMR) in this retrospective cohort study. The occurrence of RUTAs was assessed for children with and without DS who were born in NYS between 1992 and 2004. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each malformation. Between 1992 and 2004, 3832 children with DS and 3 411 833 without DS were born in NYS. The prevalence of RUTAs in the DS population was 3.2%, compared with 0.7% in the NYS population (OR: 4.5 [95% CI: 3.8 -5.4]). Children with DS had significantly increased risks of anterior urethral obstruction (OR: 29.7 [95% CI: 4.0 -217.7]), cystic dysplastic kidney (OR: 4.5 [95% CI: 1.5-14.1]), hydronephrosis (OR: 8.7 [95% CI: 6.8 -11.0]), hydroureter (OR: 8.5 [95% CI: 3.5-20.4]), hypospadias (OR: 2.0 [95% CI: 1.4 -2.9]), posterior urethral valves (OR: 7.1 [95% CI: 1.8 -28.8]), prune belly syndrome (OR: 11.9 [95% CI: 1.6 - 85.4]), and renal agenesis (OR: 5.4 [95% CI: 2.8 -10.4]). There was no significantly increased risk of ectopic kidney (OR: 1.6 [95% CI: 0.2-11.2]) or ureteropelvic junction obstruction (OR: 1.4 [95% CI: 0.2-9.9]) in the DS population. Children with DS have significantly increased risks of RUTAs.

BackgroundSynaptic density loss has been proposed as a major neuronal mechanism through which cognition degrades in Alzheimer’s disease (AD). PET imaging studies have observed synaptic density change across the AD continuum using SV2A radiotracer [11C]UCB‐J. Recent work from the SYNAPSE study revealed strong associations between neurofibrillary tau burden and reduced synaptic density in older adults (DiFilippo, under review). These analyses are actively being extended to the Down syndrome (DS) population. Individuals with DS carry a genetic risk for AD, resulting in early and rapid accumulation of AD pathology. In the Alzheimer Biomarkers Consortium – Down syndrome (ABC‐DS) study, [11C]UCB‐J PET imaging is underway. This project will characterize synaptic density relative to the accelerated accumulation of AD neuropathology in DS.Method[11C]UCB‐J PET analysis techniques require validation before extending their use to the DS population. Brain morphology differences in adults with DS limit the efficacy of spatial processing algorithms designed for the neurotypical (NT) population. Therefore, DS‐specific brain templates for T1 MR and [11C]UCB‐J PET images will be created. Additionally, kinetic modelling has not been performed with UCB‐J in the DS population, and only late‐time window uptake ratios (i.e. SUVR) will be quantified to minimize experimental burden. To evaluate SUVR PET methods in the DS cohort, equivalent SUVR methods will be explored in a NT cohort, using DVR as a reference to determine optimal windowing parameters. The relationship between regional tau and SV2A can then be investigated in both the NT and DS populations.ResultA DS‐specific T1 MRI template has been developed (LeMerise; 2022), and a [11C]UCB‐J PET template is being created. SUVR windowing for 40‐70 minute acquisitions was compared to DVR in a NT cohort (Figure 1) and compared with the same parameters in a DS cohort (Figure 2). In a separate NT cohort (n = 94; age=56.3‐89.8 years), a strong relationship between hippocampal tau and SV2A was observed (r=‐0.49, p <0.001), with a weaker association in the entorhinal cortex (r=‐0.24, p = 0.02). Tau analyses are actively being performed for the DS population.ConclusionUnderstanding the distribution of SV2A in DS will provide insight on changes to synaptic density in populations with accelerated AD neuropathology.

BackgroundSynaptic density loss has been proposed as a major neuronal mechanism through which cognition degrades in Alzheimer's disease (AD). PET imaging studies have observed synaptic density change across the AD continuum using SV2A radiotracer [11C]UCB‐J. Recent work from the SYNAPSE study revealed strong associations between neurofibrillary tau burden and reduced synaptic density in older adults (DiFilippo, under review). These analyses are actively being extended to the Down syndrome (DS) population. Individuals with DS carry a genetic risk for AD, resulting in early and rapid accumulation of AD pathology. In the Alzheimer Biomarkers Consortium – Down syndrome (ABC‐DS) study, [11C]UCB‐J PET imaging is underway. This project will characterize synaptic density relative to the accelerated accumulation of AD neuropathology in DS.Method[11C]UCB‐J PET analysis techniques require validation before extending their use to the DS population. Brain morphology differences in adults with DS limit the efficacy of spatial processing algorithms designed for the neurotypical (NT) population. Therefore, DS‐specific brain templates for T1 MR and [11C]UCB‐J PET images will be created. Additionally, kinetic modelling has not been performed with UCB‐J in the DS population, and only late‐time window uptake ratios (i.e. SUVR) will be quantified to minimize experimental burden. To evaluate SUVR PET methods in the DS cohort, equivalent SUVR methods will be explored in a NT cohort, using DVR as a reference to determine optimal windowing parameters. The relationship between regional tau and SV2A can then be investigated in both the NT and DS populations.ResultA DS‐specific T1 MRI template has been developed (LeMerise; 2022), and a [11C]UCB‐J PET template is being created. SUVR windowing for 40‐70 minute acquisitions was compared to DVR in a NT cohort (Figure 1) and compared with the same parameters in a DS cohort (Figure 2). In a separate NT cohort (n = 94; age=56.3‐89.8 years), a strong relationship between hippocampal tau and SV2A was observed (r=‐0.49, p <0.001), with a weaker association in the entorhinal cortex (r=‐0.24, p = 0.02). Tau analyses are actively being performed for the DS population.ConclusionUnderstanding the distribution of SV2A in DS will provide insight on changes to synaptic density in populations with accelerated AD neuropathology.

No definitive peripheral biological marker has yet been found to correlate with Alzheimer's disease (AD). This study investigated the role of macrocytosis as a marker which could significantly improve our understanding of AD in the Down's syndrome (DS) population. This study investigated the possible association between raised mean corpuscular volume (MCV) and AD in 150 adults with DS over a five year study period. A raised MCV is common in the DS population. A statistically significant association between a further elevated MCV and clinically diagnosed AD in adults with DS was found. The findings suggest that further research into the association between macrocytosis and DS could improve our understanding of the underlying biological mechanisms of AD. The measurement of MCV should be undertaken in all DS individuals with a diagnosis of possible or definite dementia. A significant raised MCV (above 97fl for males and 99fl for females) may further improve the clinical diagnosis. A single MCV measurement, however, cannot be recommended as a diagnostic test for AD in adults with DS.

HIGH PREVALENCE OF VASCULAR AND METABOLIC RISK FACTORS AMONG DOWN SYNDROME PATIENTS WITH ALZHEIMER’S DISEASE: A SURVEY REPORT OF THE NATIONAL DOWN SYNDROME REGISTRY (DS-CONNECT)

Atlantoaxial subluxation (AAS) is a diagnosis describing misalignment of the C1 vertebra relative to C2. Excessive translation of this joint, located adjacent to the medullary brain stem, can lead to devastating neurological consequences. A higher prevalence of AAS within the Down syndrome (DS) population has been well-established. This study aims to establish a prevalence rate of DS in patients hospitalized for AAS and compare outcomes between AAS patients with and without DS. This study utilized the National Inpatient Sample (NIS) provided by the Healthcare Cost and Utilization Project (HCUP). In accordance with HCUP 2023 Clinical Classifications Software Refined files, data were queried using the International Classification of Diseases 10th Edition codes for DS and AAS. Demographics, comorbidities, hospital course, and outcomes were examined and compared using binary and linear multivariate regression. IBM SPSS software was used for data analysis. Of the 213,095 patients in the NIS database admitted between 2016 and 2020 with AAS as their primary diagnosis, 7.2% were DS patients. DS patients were significantly younger (26.56 ± 20.81 vs. 49.39 ± 27.63, P < 0.01), less likely to be female (33.30% vs. 52.10%), and had fewer comorbidities (diabetes mellitus, hypertension, and hyperlipidemia) than non-DS patients. There was no significant difference in likelihood to undergo surgical fusion between DS patients and non-DS patients with AAS. This large-scale study using NIS data determined that 7.2% of all patients admitted to hospitals for AAS are DS patients. The analysis of demographics, hospital course, and outcomes can influence the development of treatment protocols for AAS in the DS population.

BACKGROUND The incidence of specific solid tumors in Down's syndrome (DS) is not well established. Testicular germ cell tumors (TGCT) might be increased in this population. METHODS The presence of TGCT among male subjects from the French department of Corrèze was recorded and literature on the subject reviewed. RESULTS A total of 120 living children and adults with DS and 17 pregnancies (12 births and 5 therapeutic abortions) were examined over an 8-year period (1987-1994). Three TGCT were diagnosed. A seminoma and an embryonal carcinoma were observed in two young adults and an intratubular germ cell neoplasm in a 22-week-old fetus. Because testicular tumors occur at an incidence rate of 4 cases per 100,000 person-years in the general population, these observations suggest a clearly increased risk of developing TGCT in the DS population. In addition, a review of the literature also shows an excess of TGCT in this population. Cryptorchidism alone, which is prevalent in individuals with DS, cannot explain this significantly increased incidence of TCGT. The authors hypothesize that an excess of luteinizing hormone and follicle-stimulating hormone gonadotropins and overexpression of the Ets-2 gene through gene dosage effect could predispose patients with DS to the development of TGCT. CONCLUSIONS Surveillance of the gonads of male patients with DS is recommended. A better understanding of the factors involved could also help to identify risk factors in the general population. Cancer 1997; 80:929-35. © 1997 American Cancer Society.

The incidence of specific solid tumors in Down's syndrome (DS) is not well established. Testicular germ cell tumors (TGCT) might be increased in this population. The presence of TGCT among male subjects from the French department of Corrèze was recorded and literature on the subject reviewed. A total of 120 living children and adults with DS and 17 pregnancies (12 births and 5 therapeutic abortions) were examined over an 8-year period (1987-1994). Three TGCT were diagnosed. A seminoma and an embryonal carcinoma were observed in two young adults and an intratubular germ cell neoplasm in a 22-week-old fetus. Because testicular tumors occur at an incidence rate of 4 cases per 100,000 person-years in the general population, these observations suggest a clearly increased risk of developing TGCT in the DS population. In addition, a review of the literature also shows an excess of TGCT in this population. Cryptorchidism alone, which is prevalent in individuals with DS, cannot explain this significantly increased incidence of TCGT. The authors hypothesize that an excess of luteinizing hormone and follicle-stimulating hormone gonadotropins and overexpression of the Ets-2 gene through gene dosage effect could predispose patients with DS to the development of TGCT. Surveillance of the gonads of male patients with DS is recommended. A better understanding of the factors involved could also help to identify risk factors in the general population.

BackgroundSleep‐related breathing disorders are commonly reported in the Down Syndrome (DS) population, but data on its prevalence and severity are scarce, especially for the adult population. The increase in life expectancy and premature aging in patients with DS reinforces the need for an assessment of sleep quality. This study evaluated sleep‐disordered breathing in adults with DS using sleep measures by polysomnography. The aim of this study is to define the association between the severity of obstructive sleep apnea (OSA) in adults with DS and the clinical diagnoses of stable cognition versus prodromal dementia and dementia. Furthermore, it was possible to correlate sleep respiratory variables in these groups.MethodAll participants underwent a sleep study Type 1 Polysomnography, analyzed according to the American Academy of Sleep Medicine (AASM). The diagnostic criteria for OSA and its severity were based on the description of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5). A multidisciplinary consensus including psychiatrists and geriatricians classified the participants into three diagnostic groups: stable cognition, prodromal demetia, and dementia. A neuropsychological assessment was carried out, according to the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX‐DS). The Kruskal‐Wallis test was applied to evaluate our results.Result3 participants had dementia (mean AHI 17,80 events/h), 7 were classified as prodromal dementia (mean AHI 42,60 events/h) and 28 were in the stable cognition group (mean AHI 36,42 events/h). It was not possible to determine statistically significant evidence between the AHI and the diagnoses. The correlation between respiratory sleep variables demonstrated a strong association between AHI, AHI in NREM sleep and ODI values. Furthermore, the higher the AHI or ODI values, the lower the minimum oxyhemoglobin saturation. However, it was not possible to observe a correlation with the mean oxyhemoglobin saturation.ConclusionStudies show that OSA is the main sleep disorder in the DS population, demonstrating the importance of early diagnosis. In our analysis, it was not possible to define a correlation between OSA and clinical diagnoses, possibly because there are few non‐control cases. Being preliminary data, clinical and polysomnographic follow‐up will support our preliminary hypotheses.

<h3>Introduction</h3> Trisomy 21, also known as Down syndrome (DS), is a clinical disorder where a third copy of chromosome 21 is present. Approximately 95% of DS are due to a meiotic nondisjunction, with the remaining 5% caused by chromosomal translocation or mosaicism. Children with DS are predisposed to recurrent respiratory infections due to a number of anatomical and immunological features. Our project investigated whether there is evidence supporting or refuting the use of antibiotic prophylaxis for recurrent respiratory infections in the DS population. <h3>Methods</h3> A systematic literature review was conducted of published medical literature within the following databases: MEDLINE, Science Direct, and The Cochrane Library. A systematic search for ongoing clinical trials and guidelines/consensus statements was performed using various clinical trial registers and professional organisation websites. Search terms included ‘DS’, ‘Trisomy 21’, ‘paediatric’, ‘respiratory infections’, ‘recurrent respiratory infections’, ‘prophylaxis’ and ‘antibiotics’. Systematic reviews, meta-analyses, randomised controlled trials, case-control studies and case-series were considered. <h3>Results</h3> A systematic search revealed 0 published articles and 0 clinical trials meeting the necessary inclusion criteria. 1 guideline was found meeting our inclusion criteria; the Nottingham Guideline which outlines the role of prophylactic antibiotics in the DS population. Given the dearth of evidence in this area, we formulated a clinical trial to investigate the utility of prophylactic antibiotics for current respiratory infections in the DS population. Azithromycin was chosen as the antibiotic of choice for its anti-inflammatory and immunomodulatory properties. Primary endpoints would be the number of respiratory infections experienced over the course of the treatment period requiring a GP or ED attendance. Secondary endpoints include the severity of respiratory infections, both the number and severity of adverse events experienced over the period of the trial, along with the patient and parent/legal guardian self-reported quality of life. <h3>Conclusion</h3> There is a current lack of evidence supporting or refuting the use of prophylactic antibiotics for recurrent respiratory infections in DS. Basic scientific studies need to be performed elucidating the role of anatomical and immunological features in predisposing children with DS to recurrent respiratory infections. Clinical trials are needed to elucidate whether prophylactic antibiotics are useful in this cohort and to investigate the optimal timing and combination of antibiotics. Guidelines are needed to support physicians in clinical decision making.

BackgroundPeople with Down syndrome (DS) have a significantly increased risk of developing early-onset Alzheimer's disease. For example, a longitudinal study by McCarron et al. (2017) found that 97% of a cohort of 77 DS patients aged 35 years and older developed dementia. Despite this high risk, administrative data on dementia prevalence in this population remain limited.ObjectiveThis study examines whether the diagnosed prevalence is lower than expected based on epidemiological data and explores differences compared to the general population.MethodsA comparative analysis of administrative dementia prevalence (2010-2019) was conducted using claims data for adults with and without DS. Prevalence rates were calculated by age and sex. Chi-square tests were applied to assess significance (p < 0.05), with Cramér's V and Phi as measures of association. Odds ratios were calculated to evaluate group differences.ResultsTotal administrative dementia prevalence was significantly higher in adults with DS (Mean Value (MV) 9.2% ± 1.7% (Standard Deviation (SD))) than those without DS (MV 3.2% ± 0.3% (SD)). Age- and sex-specific analyses also revealed notable differences. For example, in the 56-60 years age group, prevalence was MV 28.7% ± 4.6% (SD) in adults with DS versus MV 0.7% ± 0.1% (SD) in those without DS.ConclusionsAlthough administrative dementia prevalence is higher among adults with DS than those without DS, observed rates appear lower than expected based on existing epidemiological data. This suggests a potential underdiagnosis of dementia in the DS population in Germany.

The study of cerebral specialization in persons with Down syndrome (DS) has revealed an anomalous pattern of organization. Specifically, persons with DS elicit a right cerebral hemisphere lateralization for receptive language and a left cerebral hemisphere lateralization for the production of simple and complex movements: a pattern quite different from the left hemisphere lateralization typically characterizing the aforementioned processes in the non-DS population. It is thought that the putative separation between speech perception and movement planning systems as well as the cost of interhemispheric integration impedes verbal-motor behaviours in persons with DS. Moreover, morphological anomalies of callosal structure may further amplify between-hemisphere communication difficulties in the DS population. In the present investigation, we employed a behavioural technique (i.e. the Poffenberger paradigm; Poffenberger) to determine whether global anomalies of callosal structure further amplify deficits in interhemispheric communication. Fourteen individuals with DS and 25 chronological age-matched and gender-equated participants without intellectual disability performed a visuomotor reaction time (RT) test with their left or right hand to visual stimuli appearing left or right of visual fixation. Typically it is reported that responses to visual stimuli appearing ipsilateral to the responding hand (i.e. the uncrossed condition) are faster than responses wherein visual stimuli and responding hand are contralaterally mapped (i.e. the crossed condition). The increased RT associated with the crossed condition is reported on the order of 4 ms and has been interpreted to reflect the physiological result of interhemispheric transmission. Not surprisingly persons with DS exhibited slower and more variable RTs relative to control counterparts. In addition, a reliable RT advantage favouring the uncrossed conditions was observed among control participants but not persons with DS. In keeping with the extant literature, RT performance of the DS group was slower and more variable than control counterparts. This finding has been interpreted to reflect an 'adaptive reaction' wherein the perceptual-motor abilities of persons with DS are not optimized to respond to externally paced stimuli. In terms of evaluating interhemispheric transmission via the Poffenberger paradigm, our results show the finite measures of explicit brain-behaviour relations characterizing so-called healthy controls are not always tenable in the DS population. Indeed, we believe such a finding underpins the aforementioned 'adaptive reaction' exemplifying preferred movement control in persons with DS.

All individuals with Down syndrome (DS) will develop full-blown Alzheimer´s disease (AD) pathology by age 40. Several genes encoded in chromosome 21, including dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), have been proven to contribute to the pathology. Phosphorylation of tau at threonine-212 (p-tau212) is very sensitive to DYRK1A phosphorylation and is increased in DSAD brain lysates. Here, we assessed the potential of this biomarker in DSAD and sporadic AD. Using single molecule array (Simoa) technology, we tested p-tau212 and p-tau181 (n=245 for plasma, n=114 matching cerebrospinal fluid [CSF] samples). We have confirmed that the levels of plasma p-tau212 are increased in the DS population and sporadic AD cases, including prodromal and mild cognitive impairment states. Plasma p-tau212 started increasing approximately when people became amyloid positron emission tomography positive. Plasma p-tau212 might have utility for theragnostics, monitoring therapy efficacy, and as a target engagement biomarker in clinical trials both in sporadic and DSAD. Plasma p-tau212 is increased in the Down syndrome(DS) population. Plasma p-tau212 increases ≈15 years before the disease onset in DSAD. Plasma p-tau212 accurately differentiates between control and disease groups. Plasma p-tau212 accurately differentiates amyloid beta (Aβ)+ and Aβ- participants.

BackgroundVirtually all adults with Down Syndrome(DS) show Alzheimer’s disease(AD)‐related pathologic change by the age of 40 years. While sex differences in Aβ‐dependent tauopathy are apparent during early sporadic AD, sex differences in the DS population remain under‐investigated. Moreover, menopause onset occurs earlier in the DS population (45 years), and it remains unknown whether menopause status and hormone therapy(HT) exposure influences Aβ‐dependent tauopathy in women with DS. In a cognitively unimpaired DS population, we investigated cross‐sectional associations between Aβ and regional tau as a function of sex, menopause‐status, and HT‐exposure.Method115 cognitively unimpaired individuals from the Alzheimer Biomarkers Consortium—Down Syndrome (Mean Age 37.9; 56 women [48%]; 13 APOEε4 carriers [11%];Table 1) underwent Pittsburgh Compound‐B/Florbetapir(Aβ‐PET) and Flortaucipir(tau‐PET). Global Aβ was transformed to centiloid scale. 10 (20.6%) women self‐reported as being menopausal. 11 (20.4%) women reported HT exposure. Four a priori tau regions previously demonstrating sex differences in sporadic AD were selected (entorhinal cortex, inferior temporal gyrus, fusiform gyrus, lateral occipital cortex). Linear regressions (covarying age) examined the sex*Aβ interaction for each tau‐PET outcome. Similar models were examined in the subset of women, investigating menopause‐status[not menopausal/menopausal]*Aβ and HT*Aβ interactions. Exploratory whole‐brain vertex‐wise tau‐PET analyses were conducted with sex*Aβ and menopause*Aβ (modelled‐separately) and a FDR threshold p=0.05.ResultThe sex*Aβ interaction showed a trend level association with tau‐PET, suggesting men exhibit elevated posterior‐temporal and lateral‐occipital tau with higher Aβ, relative to women (Figure 1). The menopause status*Aβ analyses indicated that menopausal women with higher Aβ exhibit significantly elevated temporal, lateral occipital and parietal tau (Figure 2). Sensitivity analyses covarying an age*Aβ interaction suggested that the menopause‐tau association was not driven solely by advancing age. Finally, higher temporal fusiform(p=0.020) and lateral occipital(p=0.004) tau‐PET signal was observed in women with HT‐exposure at higher levels of Aβ, relative to women without exposure.ConclusionSex differences in the Aβ‐tau association were marginal and require additional investigation. Menopause‐status and HT‐exposure influenced the association between Aβ and regional tau. While our results lack statistical power and should be replicated in larger DS populations, the findings suggest that sex‐specific biomarker profiles in DS may help determine sex‐specific pathways and hormonal mechanisms underlying increased risk of dementia.

BackgroundVirtually all adults with Down Syndrome(DS) show Alzheimer’s disease(AD)‐related pathologic change by the age of 40 years. While sex differences in Aß‐dependent tauopathy are apparent during early sporadic AD, sex differences in the DS population remain under‐investigated. Moreover, menopause onset occurs earlier in the DS population(45 years), and it remains unknown whether menopause status and hormone therapy(HT) exposure influences Aß‐dependent tauopathy in women with DS. In a cognitively unimpaired DS population, we investigated cross‐sectional associations between Aß and regional tau as a function of sex, menopause‐status, and HT‐exposure.Method115 cognitively unimpaired individuals from the Alzheimer Biomarkers Consortium—Down Syndrome (Mean Age 37.9; 56 women [48%]; 13 APOEe4 carriers [11%];Table 1) underwent Pittsburgh Compound‐B/Florbetapir(Aß‐PET) and Flortaucipir(tau‐PET). Global Aß was transformed to centiloid scale. 10 (20.6%) women self‐reported as being menopausal. 11 (20.4%) women reported HT exposure. Four a priori tau regions previously demonstrating sex differences in sporadic AD were selected (entorhinal cortex, inferior temporal gyrus, fusiform gyrus, lateral occipital cortex). Linear regressions (covarying age) examined the sex*Aß interaction for each tau‐PET outcome. Similar models were examined in the subset of women, investigating menopause‐status[not menopausal/menopausal]*Aß and HT*Aß interactions. Exploratory whole‐brain vertex‐wise tau‐PET analyses were conducted with sex*Aß and menopause*Aß (modelled‐separately) and a FDR threshold p = 0.05.ResultThe sex*Aß interaction showed a trend level association with tau‐PET, suggesting men exhibit elevated posterior‐temporal and lateral‐occipital tau with higher Aß, relative to women (Fig 1). The menopause status*Aß analyses indicated that menopausal women with higher Aß exhibit significantly elevated temporal, lateral occipital and parietal tau (Fig 2). Sensitivity analyses covarying an age*Aß interaction suggested that the menopause‐tau association was not driven solely by advancing age. Finally, higher temporal fusiform (p = 0.020) and lateral occipital (p = 0.004) tau‐PET signal was observed in women with HT‐exposure at higher levels of Aß, relative to women without exposure.ConclusionSex differences in the Aß‐tau association were marginal and require additional investigation. Menopause‐status and HT‐exposure influenced the association between Aß and regional tau. While our results lack statistical power and should be replicated in larger DS populations, the findings suggest that sex‐specific biomarker profiles in DS may help determine sex‐specific pathways and hormonal mechanisms underlying increased risk of dementia.