Journal of Clinical Medicine

Editorial

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4 pages, 177 KiB

Open AccessEditorial

Aging in Down Syndrome: Latest Clinical Advances and Prospects

by Alessandra C. Martini, Melissa J. Alldred and Ann-Charlotte Granholm

J. Clin. Med. 2021, 10(21), 5037; https://doi.org/10.3390/jcm10215037 - 28 Oct 2021

Cited by 3 | Viewed by 1516

Abstract

Down syndrome (DS), or trisomy 21, is the most common genetic cause of intellectual disability [...] Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

Research

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23 pages, 4927 KiB

Open AccessArticle

Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain

by Aurélie Ledreux, Sarah Thomas, Eric D. Hamlett, Camille Trautman, Anah Gilmore, Emily Rickman Hager, Daniel A. Paredes, Martin Margittai, Juan Fortea and Ann-Charlotte Granholm

J. Clin. Med. 2021, 10(17), 3931; https://doi.org/10.3390/jcm10173931 - 31 Aug 2021

Cited by 13 | Viewed by 3396

Abstract

Individuals with Down syndrome (DS) exhibit Alzheimer’s disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS [...] Read more.

Individuals with Down syndrome (DS) exhibit Alzheimer’s disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS contains p-Tau at an early age. The goal of the study was to investigate whether NDEVs isolated from the blood of individuals with DS can spread Tau pathology in the brain of wildtype mice. We purified NDEVs from the plasma of patients with DS-AD and controls and injected small quantities using stereotaxic surgery into the dorsal hippocampus of adult wildtype mice. Seeding competent Tau conformers were amplified in vitro from DS-AD NDEVs but not NDEVs from controls. One month or 4 months post-injection, we examined Tau pathology in mouse brains. We found abundant p-Tau immunostaining in the hippocampus of the mice injected with DS-AD NDEVs compared to injections of age-matched control NDEVs. Double labeling with neuronal and glial markers showed that p-Tau staining was largely found in neurons and, to a lesser extent, in glial cells and that p-Tau immunostaining was spreading along the corpus callosum and the medio-lateral axis of the hippocampus. These studies demonstrate that NDEVs from DS-AD patients exhibit Tau seeding capacity and give rise to tangle-like intracellular inclusions. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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26 pages, 36283 KiB

Open AccessArticle

Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome

by David G. Moreno, Emma C. Utagawa, Nicoleta C. Arva, Kristian T. Schafernak, Elliott J. Mufson and Sylvia E. Perez

J. Clin. Med. 2021, 10(15), 3414; https://doi.org/10.3390/jcm10153414 - 31 Jul 2021

Cited by 4 | Viewed by 2454

Abstract

Although the prenatal hippocampus displays deficits in cellular proliferation/migration and volume, which are later associated with memory deficits, little is known about the effects of trisomy 21 on postnatal hippocampal cellular development in Down syndrome (DS). We examined postnatal hippocampal neuronal profiles from [...] Read more.

Although the prenatal hippocampus displays deficits in cellular proliferation/migration and volume, which are later associated with memory deficits, little is known about the effects of trisomy 21 on postnatal hippocampal cellular development in Down syndrome (DS). We examined postnatal hippocampal neuronal profiles from autopsies of DS and neurotypical (NTD) neonates born at 38-weeks’-gestation up to children 3 years of age using antibodies against non-phosphorylated (SMI-32) and phosphorylated (SMI-34) neurofilament, calbindin D-_28k (Calb), calretinin (Calr), parvalbumin (Parv), doublecortin (DCX) and Ki-67, as well as amyloid precursor protein (APP), amyloid beta (Aβ) and phosphorylated tau (p-tau). Although the distribution of SMI-32-immunoreactive (-ir) hippocampal neurons was similar at all ages in both groups, pyramidal cell apical and basal dendrites were intensely stained in NTD cases. A greater reduction in the number of DCX-ir cells was observed in the hippocampal granule cell layer in DS. Although the distribution of Calb-ir neurons was similar between the youngest and oldest NTD and DS cases, Parv-ir was not detected. Conversely, Calr-ir cells and fibers were observed at all ages in DS, while NTD cases displayed mainly Calr-ir fibers. Hippocampal APP/Aβ-ir diffuse-like plaques were seen in DS and NTD. By contrast, no Aβ_1–42 or p-tau profiles were observed. These findings suggest that deficits in hippocampal neurogenesis and pyramidal cell maturation and increased Calr immunoreactivity during early postnatal life contribute to cognitive impairment in DS. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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7 pages, 236 KiB

Open AccessArticle

Association between Inflammatory Conditions and Alzheimer’s Disease Age of Onset in Down Syndrome

by Florence Lai, Nathaniel Mercaldo, Cassandra M. Wang, Giovi G. Hersch and Herminia Diana Rosas

J. Clin. Med. 2021, 10(14), 3116; https://doi.org/10.3390/jcm10143116 - 15 Jul 2021

Cited by 6 | Viewed by 2779

Abstract

Adults with Down syndrome (DS) have an exceptionally high prevalence of Alzheimer disease (AD), with an earlier age of onset compared with the neurotypical population. In addition to beta amyloid, immunological processes involved in neuroinflammation and in peripheral inflammatory/autoimmune conditions are thought to [...] Read more.

Adults with Down syndrome (DS) have an exceptionally high prevalence of Alzheimer disease (AD), with an earlier age of onset compared with the neurotypical population. In addition to beta amyloid, immunological processes involved in neuroinflammation and in peripheral inflammatory/autoimmune conditions are thought to play important roles in the pathophysiology of AD. Individuals with DS also have a high prevalence of autoimmune/inflammatory conditions which may contribute to an increased risk of early AD onset, but this has not been studied. Given the wide range in the age of AD onset in those with DS, we sought to evaluate the relationship between the presence of inflammatory conditions and the age of AD onset. We performed a retrospective study on 339 adults with DS, 125 who were cognitively stable (CS) and 214 with a diagnosis of AD. Data were available for six autoimmune conditions (alopecia, celiac disease, hypothyroidism, psoriasis, diabetes and vitamin B12 deficiency) and for one inflammatory condition, gout. Gout was associated with a significant delay in the age of AD onset by more than 2.5 years. Our data suggests that inflammatory conditions may play a role in the age of AD onset in DS. Further studies are warranted. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

14 pages, 2491 KiB

Open AccessArticle

Adiponectin Modulation by Genotype and Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer’s Disease

by Melissa J. Alldred, Sang Han Lee and Stephen D. Ginsberg

J. Clin. Med. 2021, 10(13), 2994; https://doi.org/10.3390/jcm10132994 - 5 Jul 2021

Cited by 7 | Viewed by 2567

Abstract

Down syndrome (DS) is a genetic disorder caused by the triplication of human chromosome 21, which results in neurological and physiological pathologies. These deficits increase during aging and are exacerbated by cognitive decline and increase of Alzheimer’s disease (AD) neuropathology. A nontoxic, noninvasive [...] Read more.

Down syndrome (DS) is a genetic disorder caused by the triplication of human chromosome 21, which results in neurological and physiological pathologies. These deficits increase during aging and are exacerbated by cognitive decline and increase of Alzheimer’s disease (AD) neuropathology. A nontoxic, noninvasive treatment, maternal choline supplementation (MCS) attenuates cognitive decline in mouse models of DS and AD. To evaluate potential underlying mechanisms, laser capture microdissection of individual neuronal populations of MCS offspring was performed, followed by RNA sequencing and bioinformatic inquiry. Results at ~6 months of age (MO) revealed DS mice (the well-established Ts65Dn model) have significant dysregulation of select genes within the Type 2 Diabetes Mellitus (T2DM) signaling pathway relative to normal disomic (2N) littermates. Accordingly, we interrogated key T2DM protein hormones by ELISA assay in addition to gene and encoded protein levels in the brain. We found dysregulation of adiponectin (APN) protein levels in the frontal cortex of ~6 MO trisomic mice, which was attenuated by MCS. APN receptors also displayed expression level changes in response to MCS. APN is a potential biomarker for AD pathology and may be relevant in DS. We posit that changes in APN signaling may be an early marker of cognitive decline and neurodegeneration. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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10 pages, 548 KiB

Open AccessArticle

The Association between Sex and Risk of Alzheimer’s Disease in Adults with Down Syndrome

by Pooja Girish Mhatre, Joseph H. Lee, Deborah Pang, Warren B. Zigman, Benjamin Tycko, Sharon J. Krinsky-McHale, Yuchen Yang, Wayne Silverman and Nicole Schupf

J. Clin. Med. 2021, 10(13), 2966; https://doi.org/10.3390/jcm10132966 - 1 Jul 2021

Cited by 9 | Viewed by 2974

Abstract

Background: Sex differences in the risk of Alzheimer’s Disease (AD) in adults with Down Syndrome (DS) have not been extensively investigated, and existing studies have found conflicting results. This study examined the effect of sex on the risk of AD in adults with [...] Read more.

Background: Sex differences in the risk of Alzheimer’s Disease (AD) in adults with Down Syndrome (DS) have not been extensively investigated, and existing studies have found conflicting results. This study examined the effect of sex on the risk of AD in adults with DS, adjusted for covariates. Methods: Adults with DS were assessed longitudinally for the development of AD. Competing risk survival analyses were used to determine the effect of sex alone and after adjustment for APOE-ε4 status, ethnicity, and level of intellectual disability (ID). Results: Sex differences were significant only in adults over 60 years of age, where men with DS were 6.32 (95% CI: 2.11–18.96, p < 0.001) times more likely to develop AD compared with age-matched women with DS. Conclusions: There is an age-associated effect of sex on the risk of AD, with men over 60 years old having six times the risk of AD compared with age-matched women, independent of APOE-ε4 status, ethnicity, and level of ID. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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32 pages, 6925 KiB

Open AccessArticle

Impaired Iron Homeostasis and Haematopoiesis Impacts Inflammation in the Ageing Process in Down Syndrome Dementia

by Ruma Raha-Chowdhury, Animesh Alexander Raha, James Henderson, Seyedeh Deniz Ghaffari, Monika Grigorova, Jessica Beresford-Webb, Kieren Allinson, Subhojit Chakraborty, Anthony Holland and Shahid H. Zaman

J. Clin. Med. 2021, 10(13), 2909; https://doi.org/10.3390/jcm10132909 - 29 Jun 2021

Cited by 4 | Viewed by 3356

Abstract

Down syndrome (DS) subjects are more likely to develop the clinical features of Alzheimer’s disease (AD) very early in the disease process due to the additional impact of neuroinflammation and because of activation of innate immunity. Many factors involved in the neuropathology of [...] Read more.

Down syndrome (DS) subjects are more likely to develop the clinical features of Alzheimer’s disease (AD) very early in the disease process due to the additional impact of neuroinflammation and because of activation of innate immunity. Many factors involved in the neuropathology of AD in DS, including epigenetic factors, innate immunity and impaired haematopoiesis, contribute significantly towards the pathophysiology and the enhanced ageing processes seen in DS and as a consequence of the triplication of genes RUNX1, S100β and OLIG2, together with the influence of proteins that collectively protect from cellular defects and inflammation, which include hepcidin, ferritin, IL-6 and TREM2. This study is aimed at determining whether genetic variants and inflammatory proteins are involved in haematopoiesis and cellular processes in DS compared with age-matched control participants, particularly with respect to neuroinflammation and accelerated ageing. Serum protein levels from DS, AD and control participants were measured by enzyme-linked immunosorbent assay (ELISA). Blood smears and post-mortem brain samples from AD and DS subjects were analysed by immunohistochemistry. RUNX1 mRNA expression was analysed by RT-PCR and in situ hybridisation in mouse tissues. Our results suggest that hepcidin, S100β and TREM2 play a critical role in survival and proliferation of glial cells through a common shared pathway. Blood smear analysis showed the presence of RUNX1 in megakaryocytes and platelets, implying participation in myeloid cell development. In contrast, hepcidin was expressed in erythrocytes and in platelets, suggesting a means of possible entry into the brain parenchyma via the choroid plexus (CP). The gene product of RUNX1 and hepcidin both play a critical role in haematopoiesis in DS. We propose that soluble TREM2, S100β and hepcidin can migrate from the periphery via the CP, modulate the blood–brain immune axis in DS and could form an important and hitherto neglected avenue for possible therapeutic interventions to reduce plaque formation. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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11 pages, 580 KiB

Open AccessArticle

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer’s Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

by James A. Hendrix, David C. Airey, Angela Britton, Anna D. Burke, George T. Capone, Ronelyn Chavez, Jacqueline Chen, Brian Chicoine, Alberto C. S. Costa, Jeffrey L. Dage, Eric Doran, Anna Esbensen, Casey L. Evans, Kelley M. Faber, Tatiana M. Foroud, Sarah Hart, Kelsey Haugen, Elizabeth Head, Suzanne Hendrix, Hampus Hillerstrom, Priya S. Kishnani, Kavita Krell, Duvia Lara Ledesma, Florence Lai, Ira Lott, Cesar Ochoa-Lubinoff, Jennifer Mason, Jessie Nicodemus-Johnson, Nicholas Kyle Proctor, Margaret B. Pulsifer, Carolyn Revta, H. Diana Rosas, Tracie C. Rosser, Stephanie Santoro, Kim Schafer, Thomas Scheidemantel, Frederick Schmitt, Brian G. Skotko, Melissa R. Stasko, Amy Talboy, Amy Torres, Kristi Wilmes, Jason Woodward, Jennifer A. Zimmer, Howard H. Feldman and William Mobley Show full author list Hide full author list

J. Clin. Med. 2021, 10(9), 1907; https://doi.org/10.3390/jcm10091907 - 28 Apr 2021

Cited by 15 | Viewed by 6180

Abstract

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the [...] Read more.

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ_1-40, Aβ_1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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12 pages, 284 KiB

Open AccessArticle

The Association between Physical Activity and CAMDEX-DS Changes Prior to the Onset of Alzheimer’s Disease in Down Syndrome

by Sarah E. Pape, R. Asaad Baksh, Carla Startin, Sarah Hamburg, Rosalyn Hithersay and Andre Strydom

J. Clin. Med. 2021, 10(9), 1882; https://doi.org/10.3390/jcm10091882 - 27 Apr 2021

Cited by 16 | Viewed by 4016

Abstract

Background: People with Down syndrome are at ultra-high risk of developing Alzheimer’s dementia. At present, there are no preventative or curative treatments. Evidence from sporadic Alzheimer’s disease literature suggests that lifestyle factors including physical activity may help maintain cognitive and functional skills and [...] Read more.

Background: People with Down syndrome are at ultra-high risk of developing Alzheimer’s dementia. At present, there are no preventative or curative treatments. Evidence from sporadic Alzheimer’s disease literature suggests that lifestyle factors including physical activity may help maintain cognitive and functional skills and reduce dementia risk. Our study aimed to explore the association between regular exercise undertaken by participants with Down syndrome and changes in dementia-related domains of cognition and function. This was to consider whether physical activity may be a protective measure to delay cognitive decline and dementia in Down syndrome. Methods: Demographic, lifestyle, and health information was collected at baseline and at a two year follow up from 214 adults with Down syndrome without dementia, who also underwent assessment using the Cambridge Examination for Mental Disorders of Older People with Down Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) and genetic analysis. Logistic regression models were used to examine the potential associations between decline in CAMDEX-DS domains and exercise whilst controlling for key variables. Results: At baseline, engaging in moderate intensity exercise was associated with a 47% reduced risk of everyday skills decline and engaging in high intensity exercise was associated with a 62% reduced risk of decline in personality and behaviour. At follow-up, high levels of exercise were associated with an 87% reduced risk of decline in personality and behaviour. Moderate intensity exercise at baseline was associated with a 62% reduction in risk of decline during the follow-up period in memory and orientation. Discussion: Based on our data it appears that regular moderate and high intensity exercise could reduce the risk of clinically detectable decline in a Down syndrome population with possible long-term benefits. People with Down syndrome may engage in less physical activity than their peers, and barriers remain which can prevent people with Down syndrome engaging in exercise. Our work highlights how important it is that people with Down syndrome are supported to be physically active, and to promote exercise as part of a healthy ageing plan. Clinical trials in this area would be justified to determine if engaging in exercise can lead to realistic improvements in maintaining functioning and delaying dementia onset in Down syndrome and to help develop guidance in this area. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

Review

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16 pages, 1010 KiB

Open AccessReview

Aging with Down Syndrome—Where Are We Now and Where Are We Going?

by Melissa J. Alldred, Alessandra C. Martini, David Patterson, James Hendrix and Ann-Charlotte Granholm

J. Clin. Med. 2021, 10(20), 4687; https://doi.org/10.3390/jcm10204687 - 13 Oct 2021

Cited by 18 | Viewed by 6401

Abstract

Down syndrome (DS) is a form of accelerated aging, and people with DS are highly prone to aging-related conditions that include vascular and neurological disorders. Due to the overexpression of several genes on Chromosome 21, for example genes encoding amyloid precursor protein ( [...] Read more.

Down syndrome (DS) is a form of accelerated aging, and people with DS are highly prone to aging-related conditions that include vascular and neurological disorders. Due to the overexpression of several genes on Chromosome 21, for example genes encoding amyloid precursor protein (APP), superoxide dismutase (SOD), and some of the interferon receptors, those with DS exhibit significant accumulation of amyloid, phospho-tau, oxidative stress, neuronal loss, and neuroinflammation in the brain as they age. In this review, we will summarize the major strides in this research field that have been made in the last few decades, as well as discuss where we are now, and which research areas are considered essential for the field in the future. We examine the scientific history of DS bridging these milestones in research to current efforts in the field. We extrapolate on comorbidities associated with this phenotype and highlight clinical networks in the USA and Europe pursuing clinical research, concluding with funding efforts and recent recommendations to the NIH regarding DS research. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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28 pages, 1988 KiB

Open AccessReview

The Clinical and Neuropathological Features of Sporadic (Late-Onset) and Genetic Forms of Alzheimer’s Disease

by Tanzil Rujeedawa, Eva Carrillo Félez, Isabel C. H. Clare, Juan Fortea, Andre Strydom, Anne-Sophie Rebillat, Antonia Coppus, Johannes Levin and Shahid H. Zaman

J. Clin. Med. 2021, 10(19), 4582; https://doi.org/10.3390/jcm10194582 - 3 Oct 2021

Cited by 12 | Viewed by 4819

Abstract

The purpose of this review is to compare and highlight the clinical and pathological aspects of genetic versus acquired Alzheimer’s disease: Down syndrome-associated Alzheimer’s disease in (DSAD) and Autosomal Dominant Alzheimer’s disease (ADAD) are compared with the late-onset form of the disease (LOAD). [...] Read more.

The purpose of this review is to compare and highlight the clinical and pathological aspects of genetic versus acquired Alzheimer’s disease: Down syndrome-associated Alzheimer’s disease in (DSAD) and Autosomal Dominant Alzheimer’s disease (ADAD) are compared with the late-onset form of the disease (LOAD). DSAD and ADAD present in a younger population and are more likely to manifest with non-amnestic (such as dysexecutive function features) in the prodromal phase or neurological features (such as seizures and paralysis) especially in ADAD. The very large variety of mutations associated with ADAD explains the wider range of phenotypes. In the LOAD, age-associated comorbidities explain many of the phenotypic differences. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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21 pages, 1307 KiB

Open AccessReview

Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

by Laia Montoliu-Gaya, Andre Strydom, Kaj Blennow, Henrik Zetterberg and Nicholas James Ashton

J. Clin. Med. 2021, 10(16), 3639; https://doi.org/10.3390/jcm10163639 - 17 Aug 2021

Cited by 15 | Viewed by 4660

Abstract

Epidemiological evidence suggests that by the age of 40 years, all individuals with Down syndrome (DS) have Alzheimer’s disease (AD) neuropathology. Clinical diagnosis of dementia by cognitive assessment is complex in these patients due to the pre-existing and varying intellectual disability, which may [...] Read more.

Epidemiological evidence suggests that by the age of 40 years, all individuals with Down syndrome (DS) have Alzheimer’s disease (AD) neuropathology. Clinical diagnosis of dementia by cognitive assessment is complex in these patients due to the pre-existing and varying intellectual disability, which may mask subtle declines in cognitive functioning. Cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, although accurate, are expensive, invasive, and particularly challenging in such a vulnerable population. The advances in ultra-sensitive detection methods have highlighted blood biomarkers as a valuable and realistic tool for AD diagnosis. Studies with DS patients have proven the potential blood-based biomarkers for sporadic AD (amyloid-β, tau, phosphorylated tau, and neurofilament light chain) to be useful in this population. In addition, biomarkers related to other pathologies that could aggravate dementia progression—such as inflammatory dysregulation, energetic imbalance, or oxidative stress—have been explored. This review serves to provide a brief overview of the main findings from the limited neuroimaging and CSF studies, outline the current state of blood biomarkers to diagnose AD in patients with DS, discuss possible past limitations of the research, and suggest considerations for developing and validating blood-based biomarkers in the future. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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16 pages, 1695 KiB

Open AccessReview

Sleep Disorders in Adults with Down Syndrome

by Sandra Giménez, Miren Altuna, Esther Blessing, Ricardo M. Osorio and Juan Fortea

J. Clin. Med. 2021, 10(14), 3012; https://doi.org/10.3390/jcm10143012 - 6 Jul 2021

Cited by 15 | Viewed by 4131

Abstract

Sleep disorders, despite being very frequent in adults with Down syndrome (DS), are often overlooked due to a lack of awareness by families and physicians and the absence of specific clinical sleep guidelines. Untreated sleep disorders have a negative impact on physical and [...] Read more.

Sleep disorders, despite being very frequent in adults with Down syndrome (DS), are often overlooked due to a lack of awareness by families and physicians and the absence of specific clinical sleep guidelines. Untreated sleep disorders have a negative impact on physical and mental health, behavior, and cognitive performance. Growing evidence suggests that sleep disruption may also accelerate the progression to symptomatic Alzheimer’s disease (AD) in this population. It is therefore imperative to have a better understanding of the sleep disorders associated with DS in order to treat them, and in doing so, improve cognition and quality of life, and prevent related comorbidities. This paper reviews the current knowledge of the main sleep disorders in adults with DS, including evaluation and management. It highlights the existing gaps in knowledge and discusses future directions to achieve earlier diagnosis and better treatment of sleep disorders most frequently found in this population. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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17 pages, 4247 KiB

Open AccessReview

Epilepsy in Down Syndrome: A Highly Prevalent Comorbidity

by Miren Altuna, Sandra Giménez and Juan Fortea

J. Clin. Med. 2021, 10(13), 2776; https://doi.org/10.3390/jcm10132776 - 24 Jun 2021

Cited by 44 | Viewed by 7149

Abstract

Individuals with Down syndrome (DS) have an increased risk for epilepsy during the whole lifespan, but especially after age 40 years. The increase in the number of individuals with DS living into late middle age due to improved health care is resulting in [...] Read more.

Individuals with Down syndrome (DS) have an increased risk for epilepsy during the whole lifespan, but especially after age 40 years. The increase in the number of individuals with DS living into late middle age due to improved health care is resulting in an increase in epilepsy prevalence in this population. However, these epileptic seizures are probably underdiagnosed and inadequately treated. This late onset epilepsy is linked to the development of symptomatic Alzheimer’s disease (AD), which is the main comorbidity in adults with DS with a cumulative incidence of more than 90% of adults by the seventh decade. More than 50% of patients with DS and AD dementia will most likely develop epilepsy, which in this context has a specific clinical presentation in the form of generalized myoclonic epilepsy. This epilepsy, named late onset myoclonic epilepsy (LOMEDS) affects the quality of life, might be associated with worse cognitive and functional outcomes in patients with AD dementia and has an impact on mortality. This review aims to summarize the current knowledge about the clinical and electrophysiological characteristics, diagnosis and treatment of epileptic seizures in the DS population, with a special emphasis on LOMEDS. Raised awareness and a better understanding of epilepsy in DS from families, caregivers and clinicians could enable earlier diagnoses and better treatments for individuals with DS. Full article

(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)

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