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Bibliothèque de publications NTG

People with Down syndrome are living longer and healthier lives than ever before. In Australia most people with Down syndrome can now expect to live on average to 60 years of age, and more than one in ten adults with Down syndrome will live to 70 years. As we get older we are all prone to age related health conditions. Older adults with Down syndrome experience some age-related conditions at a younger age and more often than people in general.  Many people are not aware that there is a link between Down syndrome and dementia. People with Down syndrome are more likely to get dementia and on average at a younger age than other people in the population. While this may be confronting to know, it is also helpful to understand the links between health and lifestyle so that you can take action to reduce the risk of dementia, recognize the signs of dementia, and do what you can to support a person with Down syndrome if they do develop dementia. This 24-page family-friendly guide was issued by Down Syndrome Australia.
Author: Dr. Jennifer Torr (Monash University)

Down Syndrome and Dementia: A Guide for Families

Caregiver resource guide

There is a paucity of research involving older autistic people, as highlighted in a number of systematic reviews. However, it is less clear whether this is changing, and what the trends might be in research on autism in later life.  We conducted a broad review of the literature by examining the number of results from a search in three databases (PubMed, Embase, PsycINFO) across four age groups: childhood, adolescence, adulthood, and older age. We also examined the abstracts of all the included articles for the older age group and categorized them under broad themes. Our database search identified 145 unique articles on autism in older age, with an additional 67 found by the authors (hence, the total number of articles in this review is 212). Since 2012, we found a 392% increase in research with older autistic people, versus 196% increase for childhood/early life, 253% for adolescence, and 264% for adult research. We identify 2012 as a point at which, year-on-year, older age autism research started increasing, with the most commonly researched areas being cognition, the brain, and genetics. However, older adult research only accounted for 0.4% of published autism studies over the past decade. nclusions: This increase reflects a positive change in the research landscape, although research with children continues to dominate. We also note the difficulty of identifying papers relevant to older age autism research, and propose that a new keyword could be created to increase the visibility and accessibility of research in this steadily growing area.

Source:  Mason D, Stewart GR, Capp SJ, Happé F. Older Age Autism Research: A Rapidly Growing Field, but Still a Long Way to Go. Autism Adulthood. 2022 Jun 1;4(2):164-172. doi: 10.1089/aut.2021.0041.

Older Age Autism Research: A Rapidly Growing Field, but Still a Long Way to Go

Journal article

Abstract: Unexplained regression in Down syndrome (URDS) has become a significant issue in clinical practice and research. This report illustrates the case of a patient with URDS treated with psychological treatment using Dohsa-hou, in addition to medication. Dohsa-hou, a form of psychological treatment, used for people with mental disorders in Asian countries. In Dohsa-hou treatment communication using body movement and physical interactions between the patient and therapist is emphasized. The intervention included relaxation procedures and empathic and communicative physical interaction with the therapist in treatment sessions, intended to alleviate the patient's psychological distress and agitation in interactions with others. After seven months, from Dohsa-hou initiation, the patient showed partial-to-moderate improvement in the NPI total symptoms ( 37%) and large improvement in caregiver's distress (59%), although some persistent symptoms remained (agitation and apathy). Although psychological treatment may be helpful, monitoring potential risks of acute aggression is necessary.

Source: Fujino, H., & Moritsugu, A.  Dohsa-hou for unexplained regression in Down syndrome in a 19-year-old man: A case report.  Clinical Case Reports, 2022, 10(5), e05827. https://doi.org/10.1002/ccr3.5827

Dohsa‐hou for unexplained regression in Down syndrome in a 19‐year‐old man: A case report

Journal article

This advisory provides a succinct summary of key elements of the GUIDE program that bear exploration with respect to the inclusion of adults with eligible beneficiaries with intellectual disability, including Down syndrome, living with dementia and their caregivers. Noted are some of the basics and intents of the GUIDE program, a rationale for a focus in creating beneficiaries with Down syndrome (and other intellectual disabilities), commentary on training of navigators, use of instruments for assessing dementia impact and recommendations of locating beneficiaries and creating alignment with GUIDE Participants.

NTG-NDSS Advisory on GUIDE and the Inclusion of Adults with Intellectual Disability & Down Syndrome and Dementia

NTG Advisory

The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step-by-step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science.

Source: Jack CR Jr, Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A, Hansson O, Ho C, Jagust W, McDade E, Molinuevo JL, Okonkwo OC, Pani L, Rafii MS, Scheltens P, Siemers E, Snyder HM, Sperling R, Teunissen CE, Carrillo MC. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Jun 27. doi: 10.1002/alz.13859. Epub ahead of print. PMID: 38934362.

Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup

Journal Article

 Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984, and they needed to be updated and revised, in vue of the scientific knowledge acquired over the last decades. The National Institute on Aging (NIA) and the Alzheimer's Association (AA) sponsored a series of advisory round table meetings to establish a revision of diagnostic and research criteria for AD. The workgroups reviewed the biomarker, epidemiological, and neuropsychological evidence, and proposed conceptual frameworks as well as operational research criteria based on the prevailing scientific evidence to date.  Three preclinical stages of AD were proposed: asymptomatic amyloidosis, asymptomatic amyloidosis+neurodegeneration, amyloidosis+neurodegeneration+subtle cognitive decline. The preclinical workgroup developed recommendations to determine the factors, which best predict the risk of progression from normal cognition to mild cognitive impairment (MCI) and AD dementia. It is necessary to refine these models with longitudinal clinical research studies. The workgroups on MCI and AD dementia sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. The symptomatic predementia phase of AD was referred to as MCI due to AD. Core clinical and cognitive criteria of MCI were proposed, the final set of criteria for MCI due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Criteria for all-cause dementia and for AD dementia were presented. Dementia caused by AD were classified in: probable AD dementia, possible AD dementia, and probable or possible AD dementia with evidence of the AD pathophysiological process, for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis.  In the revised criteria, a conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes. The core clinical criteria of the recommendations regarding MCI due to AD and AD dementia are intended to guide diagnosis in the clinical setting whereas the recommendations of the preclinical AD workgroup are intended purely for research purposes and do not have any clinical implications. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. 

Source:  Croisile B, Auriacombe S, Etcharry-Bouyx F, Vercelletto M; National Institute on Aging (u.s.); Alzheimer Association. Les nouvelles recommandations 2011 du National Institute on Aging et de l'Alzheimer's Association sur le diagnostic de la maladie d'Alzheimer : stades précliniques, mild cognitive impairment et démence [The new 2011 recommendations of the National Institute on Aging and the Alzheimer's Association on diagnostic guidelines for Alzheimer's disease: Preclinal stages, mild cognitive impairment, and dementia]. Rev Neurol (Paris). 2012 Jun;168(6-7):471-82. French. doi: 10.1016/j.neurol.2011.11.007. Epub 2012 May 12. PMID: 22579080.

The new 2011 recommendations of the National Institute on Aging and the Alzheimer's Association on diagnostic guidelines for Alzheimer's disease: Preclinal stages, mild cognitive impairment, and dementia

Journal Article

Amyloid-β (Aβ) plaques and aggregated tau are two core mechanisms that contribute to the clinical deterioration of Alzheimer’s disease (AD). Recently, targeted-Aβ plaque reduction immunotherapies have been explored for their efficacy and safety as AD treatment. This systematic review critically reviews the latest evidence of Donanemab, a humanized antibody that targets the reduction in Aβ plaques, in AD patients. Comprehensive systematic search was conducted across PubMed/MEDLINE, CINAHL Plus, Web of Science, Cochrane, and Scopus. This study adhered to PRISMA Statement 2020 guidelines. Adult patients with Alzheimer’s disease being intervened with Donanemab compared to placebo or standard of care in the clinical trial setting were included. A total of 396 patients across four studies received either Donanemab or a placebo (228 and 168 participants, respectively). The Aβ-plaque reduction was found to be dependent upon baseline levels, such that lower baseline levels had complete amyloid clearance (<24.1 Centiloids). There was a slowing of overall tau levels accumulation as well as relatively reduced functional and cognitive decline noted on the Integrated Alzheimer’s Disease Rating Scale by 32% in the Donanemab arm. The safety of Donanemab was established with key adverse events related to Amyloid-Related Imaging Abnormalities (ARIA), ranging between 26.1 and 30.5% across the trials. There is preliminary support for delayed cognitive and functional decline with Donanemab among patients with mild-to-moderate AD. It remains unclear whether Donenameb extends therapeutic benefits that can modify and improve the clinical status of AD patients. Further trials can explore the interplay between Aβ-plaque reduction and toxic tau levels to derive meaningful clinical benefits in AD patients suffering from cognitive impairment.

Source: Rashad, A., Rasool, A., Shaheryar, M., Sarfraz, A., Sarfraz, Z., Robles-Velasco, K., & Cherrez-Ojeda, I. (2022). Donanemab for Alzheimer's Disease: A Systematic Review of Clinical Trials. Healthcare (Basel, Switzerland), 11(1), 32. https://doi.org/10.3390/healthcare11010032

Donanemab for Alzheimer's Disease: A Systematic Review of Clinical Trials.

Journal article

At least 250 000 people in Canada live with mild dementia, and 1.3 million live with mild cognitive impairment. Alzheimer disease is implicated in 60%–70% of cases of dementia and 30%–77% of cases of mild cognitive impairment.4,5 There are no recommended medications for treating people in Canada with mild cognitive impairment or dementia caused by Alzheimer disease.  No disease-modifying medications for the treatment of Alzheimer disease have been approved in Canada. Lecanemab was the first disease-modifying medication for Alzheimer disease to be granted full approval by the US Food and Drug Administration, and a second such medication — donanemab — is under review by the agency; lecanemab is under review by Health Canada.  If disease-modifying medications for Alzheimer disease are approved by Health Canada, substantial planning at the health system level is needed to support their implementation, because of high medication costs, and a clear need for post-marketing surveillance, given limited certainty of effect from existing trial data.  We discuss disease-modifying medications for Alzheimer disease that have recently been brought to market and approved for use in other jurisdictions, as these may become accessible in Canada in due course.

Disease-modifying drugs for Alzheimer disease: implications for people in Canada

Journal article

An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease.  Since 2017, an international consortium of DS clinics assembled a database of patients with unexplained regression and age- and sex-matched controls. Standardized data on clinical symptoms and tiered medical evaluations were collected. Elements of the proposed definition of unexplained regression in DS were analyzed by paired comparisons between regression cases and matched controls.  We identified 35 patients with DS and unexplained regression, with a mean age at regression of 17.5 years. Diagnostic features differed substantially between regression cases and matched controls (p < 0.001 for all but externalizing behaviors). Patients with regression had four times as many mental health concerns (p < 0.001), six times as many stressors (p < 0.001), and seven times as many depressive symptoms (p < 0.001). Tiered medical evaluation most often identified abnormalities in vitamin D 25-OH levels, polysomnograms, thyroid peroxidase antibodies, and celiac screens. Analysis of the subset of patients with nondiagnostic medical evaluations reinforced the proposed definition.  Our case-control evidence supports a proposed definition of unexplained regression in Down syndrome. Establishing this clinical definition supports future research and investigation of an underlying mechanism. 

Source: Santoro SL, Cannon S, Capone G, Franklin C, Hart SJ, Hobensack V, Kishnani PS, Macklin EA, Manickam K, McCormick A, Nash P, Oreskovic NM, Patsiogiannis V, Steingass K, Torres A, Valentini D, Vellody K, Skotko BG. Unexplained regression in Down syndrome: 35 cases from an international Down syndrome database. Genet Med. 2020 Apr;22(4):767-776. doi: 10.1038/s41436-019-0706-8. Epub 2019 Nov 26.

Unexplained regression in Down syndrome: 35 cases from an international Down syndrome database

Journal article

Down syndrome (DS) is one of the most frequent genetic disorders and represents the first cause of intellectual disability of genetic origin. While the majority of patients with DS follow a harmonious evolution, an unusual neurodevelopmental regression may occur, distinct from that described in the context of autism spectrum disorders, called down syndrome regression disorder (DSRD). Based on four patients, two males and two females, with age range between 20 and 24, treated at the Reference Center for Rare Psychiatric Disorders of the GHU Paris Psychiatry and Neurosciences [Pôle hospitalo-universitaire d’Évaluation Prévention et Innovation Thérapeutique (PEPIT)], we describe this syndrome, discuss its etiologies and propose therapeutic strategies. DSRD often occurs in late adolescence. There is a sudden onset of language disorders, loss of autonomy and daily living skills, as well as behavioral symptoms such as depression, psychosis, or catatonia. These symptoms are non-specific and lead to an overlap with other diagnostic categories, thus complicating diagnosis. The etiologies of the syndrome are not clearly identified but certain predispositions of patients with trisomy 21 have suggested an underlying immune-mediated mechanism. Symptomatic therapeutic approaches (serotonergic antidepressants, atypical antipsychotics, benzodiazepines) were not effective, and generally associated with poor tolerance. Etiological treatments, including anti-inflammatory drugs and corticosteroids, led to partial or good recovery in the four cases. Early recognition of regressive symptoms and rapid implementation of adapted treatments are required to improve the quality of life of patients and their families.

Source: Bonne S, Iftimovici A, Mircher C, Conte M, Louveau C, Legrand A, Danset-Alexandre C, Cannarsa C, Debril A, Consoli A, Krebs MO, Ellul P, Chaumette B. Down syndrome regression disorder, a case series: Clinical characterization and therapeutic approaches. Front Neurosci. 2023 Feb 23;17:1126973. doi: 10.3389/fnins.2023.1126973.

Down syndrome regression disorder, a case series: Clinical characterization and therapeutic approaches

Journal article

To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome. There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area.  The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome.  During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on "other" studies) as were diagnostic criteria (96% agreement).  The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.

Source: Santoro JD, Patel L, Kammeyer R, Filipink RA, Gombolay GY, Cardinale KM, Real de Asua D, Zaman S, Santoro SL, Marzouk SM, Khoshnood M, Vogel BN, Tanna R, Pagarkar D, Dhanani S, Ortega MDC, Partridge R, Stanley MA, Sanders JS, Christy A, Sannar EM, Brown R, McCormick AA, Van Mater H, Franklin C, Worley G, Quinn EA, Capone GT, Chicoine B, Skotko BG, Rafii MS. Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus. Front Neurol. 2022 Jul 15;13:940175. doi: 10.3389/fneur.2022.940175.

Assessment and diagnosis of Down syndrome regression disorder: International expert consensus

Journal article

 Down Syndrome Regression Disorder (DSRD) is a diagnosis of exclusion. Psychiatric and neuroimmunologic etiologies have been proposed although the exact etiology remains unknown. This study sought to review non-DSRD diagnoses at a large quaternary medical center specializing in the diagnosis of DSRD and compare clinical characteristics between those diagnosed with DSRD and those with non-DSRD diagnoses.  The authors performed a single-center retrospective, chart-based, review of referrals for developmental regression in individuals with Down syndrome.  Two hundred and sixty-six individuals were evaluated for DSRD and of these, 54 (20%) ultimately had alternative diagnoses. Individuals with DSRD were more likely to have shorter nadir to clinical symptoms (p = 0.01, 95% CI: 0.36-0.47) and have preceding triggers (p < 0.001, 95% CI: 1.13-1.43) compared to those with alternative diagnoses. Individuals with non-DSRD diagnoses were more likely to be born premature (p = 0.01, 95% CI: 0.51-0.87) and have a history of epilepsy (p = 0.01, 95% CI: 0.23-0.77) but were also less likely to have a history of cytokine abnormalities on bloodwork (p < 0.001, 95% CI: 1.19-1.43) and have catatonia (p < 0.001, 95% CI: 1.54-2.17). The majority of alternative diagnoses (41/54, 76%) were autism spectrum disorder. In these cases, symptoms were more likely to be longstanding (symptoms > 12 months) and earlier onset (median 8 years, IQR: 6-11). Other diagnoses included epilepsy (5/54, 9%), celiac disease (5/54, 9%), cerebrovascular disease (3/54, 6%).  This study identifies that 20% of individuals referred with concerns for DSRD have alternative diagnoses. The majority of these diagnoses were autism, but rare treatable conditions were also identified, highlighting the importance of a thorough neurodiagnostic assessment.

Source:  Santoro JD, Khoshnood MM, Nguyen L, Vogel BN, Boyd NK, Paulsen KC, Rafii MS. Alternative Diagnoses in the Work Up of Down Syndrome Regression Disorder. J Autism Dev Disord. 2023 Aug 16. doi: 10.1007/s10803-023-06057-9. Epub ahead of print.

Alternative diagnoses in the work up of Down syndrome regression disorder

Journal article

The accuracy of the National Task Group-Early Detection Screen for Dementia (NTG-EDSD) was evaluated in a sample of 185 adults with Down syndrome (DS), emphasizing 'mild cognitive impairment (MCI-DS)'.  Knowledgeable informants were interviewed with the NTG-EDSD, and findings were compared to an independent dementia status rating based on consensus review of detailed assessments of cognition,  functional abilities and health status (including physician examination).  Results indicated that sections of the NTG-EDSD were sensitive to MCI-DS, with one or more concerns within the 'Memory' or 'Language and Communication' domains being most informative. The NTG-EDSD is a useful tool for evaluating dementia status, including MCI-DS. However, estimates of sensitivity and specificity, even for detecting frank dementia, indicated that NTG-EDSD findings need to be supplemented by additional sources of relevant information to achieve an acceptable level of diagnostic/screening accuracy. 

Source: Silverman W, Krinsky-McHale SJ, Lai F, Diana Rosas H, Hom C, Doran E, Pulsifer M, Lott I, Schupf N; Alzheimer’s Disease in Down Syndrome (ADDS) Consortium. Evaluation of the National Task Group-Early Detection Screen for Dementia: Sensitivity to 'mild cognitive impairment' in adults with Down syndrome. J Appl Res Intellect Disabil. 2021 May;34(3):905-915. doi: 10.1111/jar.12849. Epub 2020 Dec 13.

Evaluation of National Task Group-Early Detection Screen for Dementia: Sensitivity to 'mild cognitive impairment' in Adults with Down Syndrome

Journal Article

By age 60, 60% of adults with Down syndrome (DS) have dementia. Detecting dementia in persons with intellectual disability (ID) can be challenging because their underlying cognitive impairment can confound presentation of dementia symptoms and because adults with ID may have difficulty reporting symptoms. The National Task Group Early Detection Screen for Dementia (NTG‐EDSD) was developed to aid detection of report of cognitive impairment in adults with ID. We implemented an educational curriculum using the NTG‐EDSD and evaluated the impact of the intervention on professional caregivers’ self‐assessed capacity to identify persons with ID and dementia. We held five in‐person training sessions for professional caregivers of persons with ID, partnering with various managed care organizations and social services agencies. We assessed knowledge and attitudes at baseline; immediately after training; and 1 week, 1 month, and 6 months after training. A total of 154 direct care workers, case managers, health‐care providers, and other social services staff attended the trainings. Satisfaction with the NTG‐EDSD training was high; 94% of attendees agreed or strongly agreed that they could use the NTG‐EDSD with their clients. After training, attendees reported a marked increase in confidence in their ability to track various health circumstances and detect functional decline in their clients, although some gains were not sustained over time. As a result of the training, one managed care organization made the NTG‐EDSD a standard part of its assessment of adults with DS starting at age 40. Social services and health‐care professionals can learn to document signs of cognitive decline in adults with ID using the NTG‐EDSD. Attendees were highly satisfied with the training, experienced an increase in confidence in their care of persons with ID, and found the NTG‐ EDSD feasible to use. Because not all gains were sustained over time, booster trainings may be necessary.

Source: Walaszek A, Albrecht T, LeCaire T, et al. Training professional caregivers to screen for report of cognitive changes in persons with intellectual disability. Alzheimer's Dement. 2022;8:e12345. 10.1002/trc2.12345

Training professional caregivers to screen for report of cognitive changes in persons with intellectual disability

Journal Article

Dementia in people with intellectual disability (ID) is frequent but hard to recognise. Evidence-based recommendations for suitable instruments are lacking. The present study set out to evaluate informant-based dementia assessment instruments and to provide evidence-based recommendations for instruments most suitable in clinical practice and research. A systematic review was conducted across ten international electronic databases. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, including a risk of bias assessment, was applied to extract information and to evaluate measurement properties and the quality of available evidence.  In total, 42 studies evaluating 18 informant-based assessment instruments were analysed. For screening purposes, we recommend the Behavioral and Psychological Symptoms of Dementia in Down Syndrome Scale (BPSD-DS), the Cognitive Scale for Down Syndrome (CS-DS), the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID), and provisionally the NTG-EDSD. For a more thorough dementia assessment, we recommend the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). Our study informs clinicians and researchers about adequate, well-evaluated dementia assessment instruments for people with ID, and highlights the need for high quality studies, especially regarding content validity.

Informant-based Assessment Instruments for Dementia in People with Intellectual Disability: A Systematic Review and Standardised Evaluation

Journal Article

This resource guidebook, developed by the New York State Office for the Aging for older adults caring for an individual with an intellectual disability, offers information to help connecting them with information and resources to begin the process of long-term planning, including financial and legal tools as well as supportive programs and services. It also covers the use of the NTG-EDSD for screening and aiding in care planning.

Future Planning Guidebook for Older Caregivers of Adults with Intellectual and Developmental Disabilities

Resource Booklet

Abstract: Prior authorization criteria for FDA-approved immunotherapeutics, among the class of anti-amyloid monoclonal antibodies (mAbs), established by state drug formulary committees, are tailored for adults with late-onset Alzheimer's disease. This overlooks adults with Down syndrome (DS), who often experience dementia at a younger age and with different diagnostic assessment outcomes. This exclusion may deny DS adults access to potential disease-modifying treatments.  To address this issue, an international expert panel convened to establish adaptations of prescribing criteria suitable for DS patients and parameters for access to CMS registries. The panel proposed mitigating disparities by modifying CMS and payer criteria to account for younger onset age, using alternative language and assessment instruments validated for cognitive decline in the DS population. The panel also recommended enhancing prescribing clinicians' diagnostic capabilities for DS and initiated awareness-raising activities within healthcare organizations. These efforts facilitated discussions with federal officials aimed at achieving equity in access to anti-amyloid immunotherapeutics, with implications for national authorities worldwide evaluating these and other new AD disease-modifying therapeutics.

Source: Hillerstrom, H., Fisher, R., Janicki, M.P. et al.  Adapting prescribing criteria for amyloid-targeted antibodies for adults with Down syndrome. Alzheimer’s & Dementia, e-Pub: 13 March 2024.
https://doi.org/10.1002/alz.13778

Adapting prescribing criteria for amyloid-targeted antibodies for adults with Down syndrome.

Journal article

Approximately 40–80% of persons with Down syndrome (DS) develop Alzheimer’s disease (AD)-like dementia by the fifth to sixth decade of life [1], a much younger age than is typically seen in sporadic AD. The onset of dementia symptoms in DS parallels the development of classic brain neuropathological lesions (i.e., amyloid plaques) similar to that evident in AD. Both disorders appears to have a similar genetic linkage, which is supported by the triplication of the gene that codes for amyloid beta (A4) precursor protein (APP) in persons with DS and an extra copy of the APP gene causes familial AD in persons without DS. Despite an overlap in the genetics of these disorders, the clinical presentation of dementia differs between persons with DS and AD. Whereas ‘forgetfulness’ is a typical symptom of early-phase dementia for persons in the general population, behavioral problems and personality changes are early signs of dementia for persons with DS. There are indications that amyloid burden begins in the frontal cortex before spreading to other brain regions in those with DS-AD, something that is not always the case in sporadic AD suggesting pathological variances between these disorders. These differences beg the question: Are the genetic and neuropathological commonalities found in DS- and AD-related dementia an associated similarity or do these disorders share a common pathogenesis? To address this query, the authors briefly review the clinical, histopathological, and genetic research supporting a putative link between dementia in DS and AD.

Source: Salehi, A., Ashford, J. W., & Mufson, E. J. (2016). The Link between Alzheimer's Disease and Down Syndrome. A Historical Perspective. Current Alzheimer research, 13(1), 2–6. https://doi.org/10.2174/1567205012999151021102914

The Link between Alzheimer’s Disease and Down Syndrome. A Historical Perspective

Journal article

Acute regression has been reported in some individuals with Down syndrome (DS), typically occurring between the teenage years and mid to late 20s. Characterized by sudden, and often unexplained, reductions in language skills, functional living skills and reduced psychomotor activity, some individuals have been incorrectly diagnosed with Alzheimer's disease (AD). This paper compares five individuals with DS who previously experienced acute regression with a matched group of 15 unaffected individuals with DS using a set of AD biomarkers. Results: While the sample was too small to conduct statistical analyses, findings suggest there are possible meaningful differences between the groups on proteomics biomarkers (e.g., NfL, total tau). Hippocampal, caudate and putamen volumes were slightly larger in the regression group, the opposite of what was hypothesized. A slightly lower amyloid load was found on the PET scans for the regression group, but no differences were noted on tau PET.  Some proteomics biomarker findings suggest that individuals with DS who experience acute regression may be at increased risk for AD at an earlier age in comparison to unaffected adults with DS. However, due to the age of the group (mean 38 years), it may be too early to observe meaningful group differences on image-based biomarkers.

Source: Handen, B., Clare, I., Laymon, C., Petersen, M.., Zaman, S.., O'Bryant, S., Minhas, D., Tudorascu, D., Brown, S., Christian, B., on behalf of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS). 
Acute regression in Down syndrome.  Brain Science, 2021, 11, 1109. https://doi.org/10.3390/brainsci11081109

Acute regression in Down syndrome

Journal article

This Viewpoint explains the genetic association between Alzheimer disease and Down syndrome and the negative impact of excluding people with Down syndrome from clinical trials on treatment for Alzheimer disease.
Source:  Rafii MS, Fortea J. Down Syndrome in a New Era for Alzheimer Disease. JAMA. 2023 Dec 12;330(22):2157-2158. doi: 10.1001/jama.2023.22924. PMID: 37991807.

Down syndrome in a new era for Alzheimer Disease

Journal article

Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline.

Objectives: Primary objective • To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives • To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. • To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling • To compare results according to differing anticholinergic scales used in medication reduction intervention trials • To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes.

Search methods: We searched CENTRAL on 22 December 2022, and we searched MEDLINE, Embase, and three other databases from inception to 1 November 2022.

Selection criteria: We included randomised controlled trials (RCTs) of interventions that aimed to reduce anticholinergic burden in older people and that investigated cognitive outcomes.

Data collection and analysis: Two review authors independently assessed studies for inclusion, extracted data, and assessed the risk of bias of included studies. The data were not suitable for meta-analysis, so we summarised them narratively. We used GRADE methods to rate our confidence in the review results.

Main results: We included three trials with a total of 299 participants. All three trials were conducted in a cognitively mixed population (some cognitively healthy participants, some participants with dementia). Outcomes were assessed after one to three months. One trial reported significantly improved performance on the Digit Symbol Substitution Test (DSST) in the intervention group (treatment difference 0.70, 95% confidence interval (CI) 0.11 to 1.30), although there was no difference between the groups in the proportion of participants with reduced anticholinergic burden. Two trials successfully reduced anticholinergic burden in the intervention group. Of these, one reported no significant difference between the intervention versus control in terms of their effect on cognitive performance measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) immediate recall (mean between-group difference 0.54, 95% CI -0.91 to 2.05), CERAD delayed recall (mean between-group difference -0.23, 95% CI-0.85 to 0.38), CERAD recognition (mean between-group difference 0.77, 95% CI -0.39 to 1.94), and Mini-Mental State Examination (mean between-group difference 0.39, 95% CI -0.96 to 1.75). The other trial reported a significant correlation between anticholinergic burden and a test of working memory after the intervention (which suggested reducing the burden improved performance), but reported no effect on multiple other cognitive measures. In GRADE terms, the results were of very low certainty. There were no reported between-group differences for any other clinical outcome we investigated. It was not possible to investigate differences according to type of reduction intervention or type of anticholinergic scale, to measure the sustainability of interventions, or to establish lessons learnt for upscaling. No trials investigated safety outcomes.

Authors' conclusions: There is insufficient evidence to reach any conclusions on the effects of anticholinergic burden reduction interventions on cognitive outcomes in older adults with or without prior cognitive impairment. The evidence from RCTs was of very low certainty so cannot support or refute the hypothesis that actively reducing or stopping prescription of medications with anticholinergic properties can improve cognitive outcomes in older people. There is no evidence from RCTs that anticholinergic burden reduction interventions improve other clinical outcomes such as mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, or neurobehavioral outcomes. Larger RCTs investigating long-term outcomes are needed. Future RCTs should also investigate potential benefits of anticholinergic reduction interventions in cognitively healthy populations and cognitively impaired populations separately.

Source: Taylor-Rowan M, Alharthi AA, Noel-Storr AH, Myint PK, Stewart C, McCleery J, Quinn TJ. Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment. Cochrane Database Syst Rev. 2023 Dec 8;12(12):CD015405. doi: 10.1002/14651858.CD015405.pub2.

Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment

Journal article

A detailed instructional on how to use simple household objects and interactions  to show proficiency in some tasks that reflect capability and neurological function. The protocol was developed for use by families or staff to record 'personal best' and for use overtime to assess continued or diminishing functional abilities.

Dalton Protocol for Recording Baseline Information

Instrument guide

Older adults engaging in regular physical activity can help create a buffer toward cognitive decline. The main aim of this study was to assess the effects of physical activity and cognitive functioning on a sample of young-old and old-old physically active adults and young-old and old-old sedentary adults. Cognitive functioning was examined using the digit span test, Wisconsin card sorting task. The National Task Group-Early Detection Screen for Dementia measure was used explore the relationship between scores and physical activity and sedentary adults. Findings from the study showed partial support for physical activity has a positive relationship with cognitive functioning. The results found Young-old adults did better on the DST than all other groups regardless of being sedentary or physically active. Young-old physically active adults, however, did better on the DST latency measure than sedentary adults while old-old physically active adults did worse on the DST latency measure compared with old-old sedentary adults. The results also found that Physically active adults had a better score on the NTG-EDSD measure compared to the sedentary adults. Findings showed no significant differences for the WCST. Future research exploring the relationship between physical activity and cognitive functioning should do so by having more control over the extraneous variables.

Source: Younan B. Cognitive Functioning Differences Between Physically Active and Sedentary Older Adults. J Alzheimers Dis Rep. 2018 May 26;2(1):93-101. doi: 10.3233/ADR-180053.

Cognitive Functioning Differences Between Physically Active and Sedentary Older Adults

Journal article

Adults with Down syndrome (DS) are at exceptionally high risk for Alzheimer’s disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments.  The article describes the development of a multi-center, longitudinal study of
biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid-based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16-month intervals), as well as genetic modifiers of AD risk and progression. Approximately 400 individuals will be enrolled in the study (more than 370 to date). The methodological approach from the administrative, clinical, neuroimaging, omics, neuropathology, and statistical cores is provided.  This represents the largest U.S.-based, multi-site, biomarker initiative of AD in DS. Findings can inform other multidisciplinary networks studying AD in the general population.  The NTG-EDSD is included among the instruments in this study.

Source:  Handen BL, Lott IT, Christian BT, Schupf N, OBryant S, Mapstone M, Fagan AM, Lee JH, Tudorascu D, Wang MC, Head E, Klunk W, Ances B, Lai F, Zaman S, Krinsky-McHale S, Brickman AM, Rosas HD, Cohen A, Andrews H, Hartley S, Silverman W; Alzheimer's Biomarker Consortium‐Down Syndrome (ABC‐DS). The Alzheimer's Biomarker Consortium-Down Syndrome: Rationale and methodology. Alzheimers Dement (Amst). 2020 Aug 3;12(1):e12065. doi: 10.1002/dad2.12065.

The Alzheimer's Biomarker Consortium‐Down Syndrome: Rationale and methodology

Journal article

Research of health outcomes in older autistic adults (≥45 years) is concerningly scarce, and little is known about whether intellectual disability and sex affect the health outcomes of this population. The aim of this study was to investigate the association between autism and physical health conditions in older adults and to examine these associations by intellectual disability and sex. Authors conducted a longitudinal, retrospective, population-based cohort study of the Swedish population born between Jan 1, 1932, and Dec 31, 1967, using linked data from the nationwide Total Population Register and the National Patient Register. They excluded individuals who died or emigrated before the age of 45 years, or with any chromosomal abnormalities. Follow-up started at age 45 years for all individuals, and ended at emigration, death, or Dec 31, 2013 (the latest date of available follow-up), whichever was soonest. Diagnoses of autism, intellectual disability, 39 age-related physical conditions, and five types of injury (outcomes) were obtained from the National Patient Register. For each outcome, they calculated 25-year cumulative incidence and used Cox models to estimate hazard ratios (HRs). All analyses were repeated separately by intellectual disability and sex. Findings Of 4200887 older adults (2063718 women [49·1%] and 2137169 men [50·9%]) in the study cohort, 5291 (0·1%) had a diagnosis of autism recorded in the National Patient Register. Older autistic adults (median follow-up 8·4 years [IQR 4·2–14·6]) had higher cumulative incidence and HRs of various physical conditions and injuries than their non-autistic counterparts (median follow-up 16·4 years [8·2–24·4]). In autistic individuals, the highest cumulative incidence was observed for bodily injuries (50·0% [95% CI 47·6–52·4]). Conditions that autistic adults were at higher risk of than were non-autistic adults included heart failure (HR 1·89 [95% CI 1·61–2·22]), cystitis (2·03 [1·66–2·49]), glucose dysregulation (2·96 [2·04–4·29]), iron deficiency anemia (3·12 [2·65–3·68]), poisoning (4·63 [4·13–5·18]), and self-harm (7·08 [6·24–8·03]). These increased risks mainly persisted regardless of intellectual disability or sex. Their data indicate that older autistic adults are at substantially increased risk of age-related physical conditions and injuries compared with non-autistic adults. These findings highlight the need for collaborative efforts from researchers, health services, and policy makers to provide older autistic individuals with the necessary support to attain healthy longevity and a high quality of life.

Source: Liu S, Larsson H, Kuja-Halkola R, Lichtenstein P, Butwicka A, Taylor MJ. Age-related physical health of older autistic adults in Sweden: a longitudinal, retrospective, population-based cohort study. Lancet Healthy Longev. 2023 Jul;4(7):e307-e315. doi: 10.1016/S2666-7568(23)00067-3. Epub 2023 Jun 6. PMID: 37295448.

Age-related physical health of older autistic adults in Sweden: a longitudinal, retrospective, population-based cohort study

Journal Article

Popular family magazine article about use of the NTG-EDSD and its applications to assessing aging adults with intellectual disability.

Dementia and Intellectual Disabilities

Magazine article

This document describes the dementia diagnosis and healthcare pathway for people with an intellectual disability in the NHS Hertfordshire area of England. The pathway aims to support a standard approach to referrals for people with an intellectual disability where symptoms indicate or there may be a concern that the individual may be affected by dementia. The pathway guides the multi-disciplinary team around the individual through the sequence of events from referral to screening and diagnosis, and post-diagnosis. The aim is to ensure that a coordinated approach is taken by the multi-disciplinary team and the individual provided with the most suitable person-centered care with respect to diagnosis and healthcare provision.  The guideline also provides information on using the NTG-EDSD for screening and assessment.

Dementia Diagnosis and Healthcare Pathway for People with a Learning Disability

Guideline document

There is a paucity of research involving older autistic people, as highlighted in a number of systematic reviews. However, it is less clear whether this is changing, and what the trends might be in research on
autism in later life. Authors conducted a broad review of the literature by examining the number of results from a search in three databases (PubMed, Embase, PsycINFO) across four age groups: childhood, adolescence, adulthood, and older age.  They also examined the abstracts of all the included articles for the older age group and categorized them under broad themes.  Their database search identified 145 unique articles on autism in older age, with an additional 67 found by the authors (hence, the total number of articles in this review is 212). Since 2012, we found a 392% increase in research with older autistic people, versus 196% increase for childhood/early life, 253% for adolescence, and 264% for adult research. They identified 2012 as a point at which, year-on-year, older age autism research started increasing, with the most commonly researched areas being cognition, the brain, and genetics. However, older adult research only accounted for 0.4% of published autism studies over the past decade. This increase reflects a positive change in the research landscape, although research with children continues to dominate. We also note the difficulty of identifying papers relevant to older age autism research, and propose that a new keyword could be created to increase the visibility and accessibility of research in this steadily growing area.

Source: Mason D, Stewart GR, Capp SJ, Happé F. Older Age Autism Research: A Rapidly Growing Field, but Still a Long Way to Go. Autism Adulthood. 2022 Jun 1;4(2):164-172. doi: 10.1089/aut.2021.0041. Epub 2022 Jun 9. PMID: 36605971; PMCID: PMC9645679.

Older Age Autism Research: A Rapidly Growing Field, but Still a Long Way to Go

Journal article

Abstract:  Autism spectrum disorder (ASD) is associated with an increased risk of early-onset dementia, new research has shown. Vivanti et al. used US medical insurance records for >1.2 million individuals aged 30–64 years to examine the prevalence of dementia over 5 years among people with a diagnosis of ASD, ASD with intellectual disability, intellectual disability alone or neither. The prevalence was highest among people with intellectual disability alone (7.10%), but was also considerably higher among people with ASD (4.04%) and people with ASD and intellectual disability (5.22%) than among the healthy population (0.97%). More research will be needed to understand the mechanisms that underlie this association.

Source:  Fyfe, I. Early-onset dementia in autism spectrum disorder. Nat Rev Neu 17, 595 (2021). https://doi.org/10.1038/s41582-021-00564-y

Early-onset dementia in autism spectrum disorder

Journal article

Autism spectrum disorder (ASD) is a lifelong disorder that requires intervention and support services for a growing geriatric population. The purpose of this paper is to examine the mean age at death of individuals with ASD and subsequent comorbidity with Alzheimer’s disease, and any form of dementia, as a whole and according to sex.  Data consisted of 1,754 individuals who had an ASD listed as one of the causes of deaths from the National Vital Statistics System with data from 1999 to 2015. In the current study, the authors present contradictory results with a mean age at death for individuals with ASD was 68 years by adjusting for changing prevalence rates. Females with ASD had a higher mean age at death than males with ASD; consistent with the trend in the sex differences in the general population. The results of the current study also indicate that individuals with ASD were, in fact, less likely than the general population to have Alzheimer’s disease or a form of dementia. However, males with ASD were significantly more likely to have acquired Alzheimer’s disease or a form of dementia as compared to females with ASD.  Guan and Li (2017) reported a mean age at death of 36 years old for individuals with ASD, which was subsequently reported in the mass media, most notably CNN. The authors contend that this study provides a more accurate estimate mean age at death.

Source:  Barnard-Brak, L., Richman, D. and Yang, Z. (2019), "Age at death and comorbidity of dementia-related disorders among individuals with autism spectrum disorder", Advances in Autism, 5(4), 293-302. https://doi.org/10.1108/AIA-11-2018-0045

Age at death and comorbidity of dementia-related disorders among individuals with autism spectrum disorder

Journal article

Autism spectrum disorder (ASD) represents a heterogeneous cluster of clinical phenotypes that are classically diagnosed by the time of adolescence. The possibility of late-life emergence of ASD has been poorly explored.  In order to more fully characterize the possibility of late-life emergence of behaviors characteristic of ASD in MCI and AD, we surveyed caregivers of 142 older persons with cognitive impairment from the University of Kentucky Alzheimer’s Disease Center Longitudinal Cohort using the Gilliam Autism Rating Scale-2.  Participants with high autism index ratings (Autism ‘Possible/Very Likely’, n=23) reported significantly (statistically and clinically) younger age at onset of cognitive impairment than those who scored in the Autism ‘Unlikely’ range (n=119): 71.14±10.9 vs. 76.65±8.25 (p = 0.034). Additionally, those in Autism ‘Possible/Very Likely’ group demonstrated advanced severity of cognitive impairment, indicated by Clinical Dementia Rating Scale Sum of Boxes scores.  Data demonstrate that ASD behaviors may appear de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies.

Source: Rhodus EK, Barber J, Abner EL, Duff DMC, Bardach SH, Caban-Holt A, Lightner D, Rowles GD, Schmitt FA, Jicha GA. Behaviors Characteristic of Autism Spectrum Disorder in a Geriatric Cohort With Mild Cognitive Impairment or Early Dementia. Alzheimer Dis Assoc Disord. 2020 Jan-Mar;34(1):66-71. doi: 10.1097/WAD.0000000000000345. PMID: 31517641; PMCID: PMC7047536.

Behaviors characteristic of Autism spectrum disorder in a geriatric cohort with mild cognitive impairment or early dementia

Journal article

Although people with intellectual disability (ID) and people with dementia have high drug prescription rates, there is a lack of studies investigating drug use among those with concurrent diagnoses of ID and dementia.  To investigate the use of antipsychotics, benzodiazepine derivatives, and drugs recommended for dementia treatment (anticholinesterases [AChEIs] and memantine) among people with ID and dementia.  Having received support available for people with ID and/or autism spectrum disorder (ASD) was used as a proxy for ID. The ID cohort consisted of 7936 individuals, aged at least 55 years in 2012, and the referent cohort of age- and sex-matched people from the general population (gPop). People with a specialists’ diagnosis of dementia during 2002–2012 were identified (ID, n = 180; gPop, n = 67), and data on prescription of the investigated drugs during the period 2006–2012 were collected.  People with ID/ASD and dementia were more likely than people with ID/ASD but without dementia to be prescribed antipsychotics (50% vs 39% over the study period; odds ratio (OR) 1.85, 95% confidence interval 1.13–30.3) and benzodiazepine derivatives (55% vs 36%; OR 2.42, 1.48–3.98). They were also more likely than people with dementia from the general population to be prescribed antipsychotics (50% vs 25%; OR 3.18, 1.59–6.34), but less likely to be prescribed AChEIs (28% vs 45%; OR 0.32, 0.16–0.64).

Source:  Axmon A, Kristensson J, Ahlström G, Midlöv P. Use of antipsychotics, benzodiazepine derivatives, and dementia medication among older people with intellectual disability and/or autism spectrum disorder and dementia. Res Dev Disabil. 2017 Mar;62:50-57. doi: 10.1016/j.ridd.2017.01.001. Epub 2017 Jan 18. PMID: 28110116.

Use of antipsychotics, benzodiazepine derivatives, and dementia medication among older people with intellectual disability and/or autism spectrum disorder and dementia

Journal article

The Food and Drug Administration on July 6, 2023 gave full approval to the Alzheimer’s drug Leqembi, and Medicare said it would cover much of its high cost, laying the foundation for widespread use of a medication that can modestly slow cognitive decline in the early stages of the disease but also carries significant safety risks.  Leqembi will be available for people with mild dementia or a pre-Alzheimer’s condition called mild cognitive impairment. The F.D.A. label instructs doctors not to treat patients without testing to confirm they have an accumulation of the protein amyloid, a hallmark of Alzheimer’s that Leqembi attacks.  The F.D.A. decision granting full approval to Leqembi means that Medicare will cover it for eligible patients.  Some patients will be unable to afford the 20 percent Medicare does not cover, possibly about $6,600 a year. Including costs of medical visits and required regular brain scans, some of which will receive Medicare reimbursement, the treatment could run to about $90,000 a year.  Doctors prescribing Leqembi will be required to submit medical information about each patient before and while they are being treated with the drug. The information will be kept in patient registries and evaluated to learn more about Leqembi’s benefits or harms.

F.D.A Widens Access to Leqembi Drug for Alzheimer's

Newspaper article

An Advisory and Consensus Statement of the Working Group on Criteria for Access to Alzheimer’s Therapeutics for Adults with Down Syndrome; experts were convened to determine prescribing criteria equivalences that would be inclusionary of adults with Down syndrome. This advisory and consensus statement is the result of the experts’ deliberations and recommendations for addressing this inequity to treatment access and includes alternative inclusionary language and modified criteria, as well as providing a roadmap for prescribers when determining eligibility for adults with Down syndrome.

Adapting Eligibility Criteria for Prescribing FDA Approved Anti-Amyloid Immunotherapeutics for Adults with Down Syndrome with Early-Stage Alzheimer’s Dementia (Statement)

Statement

A severe impairment of cognitive function characterizes dementia. Mild cognitive impairment represents a transition between normal cognition and dementia. The frequency of cognitive changes is higher in women than in men. Based on this fact, hormonal factors likely contribute to cognitive decline. In this sense, cognitive complaints are more common near menopause, a phase marked by a decrease in hormone levels, especially estrogen. Additionally, a tendency toward worsened cognitive performance has been reported in women during menopause. Vasomotor symptoms (hot flashes, sweating, and dizziness), vaginal dryness, irritability and forgetfulness are common and associated with a progressive decrease in ovarian function and a subsequent reduction in the serum estrogen concentration. Hormone therapy (HT), based on estrogen with or without progestogen, is the treatment of choice to relieve menopausal symptoms. The studies conducted to date have reported conflicting results regarding the effects of HT on cognition. This article reviews the main aspects of menopause and cognition, including the neuroprotective role of estrogen and the relationship between menopausal symptoms and cognitive function. We present and discuss the findings of the central observational and interventional studies on HT and cognition.

Source:  Conde DM, Verdade RC, Valadares ALR, Mella LFB, Pedro AO, Costa-Paiva L. Menopause and cognitive impairment: A narrative review of current knowledge. World J Psychiatry. 2021 Aug 19;11(8):412-428. doi: 10.5498/wjp.v11.i8.412.

Menopause and cognitive impairment: A narrative review of current knowledge

Journal article

There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD.

Source:  Compton, J., Van Amelsvoort, T., Murphy, D.  HRT and its effect on normal ageing of the brain and dementia. British Journal of Clinical Pharmacology, 2001, Dec., 52(6), 647-653.

HRT and its effect on normal ageing of the brain and dementia

Journal article

This NTG advisory addresses an issue that many community-based organizations may encounter when state officials must attest as to whether "heightened scrutiny" is needed to determine whether small dementia-capable group homes should be included in their HCBS waivers.  The NTG contends that supporting specialized services for adults with intellectual disability living with dementia in group homes is in the spirit of both the Americans with Disabilities Act, as amended, and the Olmstead Decision, as it provides for safe housing in a least restrictive setting in the community, with specialized services that are appropriate to meet the needs of individuals with progressively diminishing cognitive and functional abilities.  The NTG believes that recognition should be given to small dementia-capable group home settings as a proven best practice support model, which upholds the rights of adults with dementia to live in the community under HCBS waivers funded by the health and social service systems in each state. When properly funded, these settings can provide personalized care, promote well-being and safety from harm, give attention to changing nutritional and dietary needs, and engage residents in activities that mitigate memory loss and cognitive decline.  The NTG also believes that recognition should be given to the advantages of small dementia-capable group homes when compared to the costs and outcomes of services that are provided in nursing facilities, because dementia-capable group homes are both less expensive on a per deim basis and more effective in enhancing the quality of life for individuals living with dementia.

Advisory on the CMS ‘Settings Rule’ and Applications for Housing Adults with Intellectual Disability Living with Dementia (Statement)

Guidelines

Menstrual status and the age of menopause were investigated in 143 Irish females with Down syndrome (DS). The average age of menopause in 42 subjects (44.7 years) was younger than in the general population. The age at onset of dementia correlated with the age of menopause. This finding may be a manifestation of accelerated aging in DS or point to estrogen deficiency being an independent risk factor for the development of Alzheimer’s dementia in DS. There are implications of this finding for possible treatments.

Source:  M. P. Cosgrave, J. Tyrrell, M. McCarron, M. Gill, B. A. Lawlor.  Age at onset of dementia and age of menopause in women with Down’s syndrome. Journal of  Intellectual Disability Research, 1999, 43(6), 461-465.

Age at onset of dementia and age of menopause in women with Down’s syndrome

Article journal

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.

Source: Schupf N, Pang D, Patel BN, Silverman W, Schubert R, Lai F, Kline JK, Stern Y, Ferin M, Tycko B, Mayeux R. Onset of dementia is associated with age at menopause in women with Down's syndrome. Ann Neurol. 2003 Oct;54(4):433-8. doi: 10.1002/ana.10677.

Onset of dementia is associated with age at menopause in women with Down's syndrome

Journal article

Diagnosing dementia in people with severe/profound intellectual (and multiple) disabilities (SPI(M)D) is complex. Whereas existing dementia screening instruments as a whole are unsuitable for this population, a number of individual items may apply. Therefore, this study aimed to identify applicable items in existing dementia screening instruments. Informant interviews about 40 people with SPI(M)D were conducted to identify applicable items in the Dementia Scale for Down Syndrome, Behavioral and Psychological Symptoms of Dementia in Down Syndrome II scale, Dementia Questionnaire for persons with Mental Retardation and Social competence Rating scale for people with Intellectual Disabilities. Among 193 items, 101 items were found applicable, categorized in β5 domains: behavioral and psychological functioning (60 items), cognitive functioning (25), motor functioning (6), activities of daily living (5) and medical comorbidities (5).  Identifying applicable items for people with SPI(M)D is an essential step in developing a dedicated dementia screening instrument for this population.

Source: Wissing, M.B.G., Dijkstra, R., van der Wal, I.A., Grootendorst, E.S.,  Hobbelen, J.S.M., van der Putten, A.A.J., De Deyn, P.P., Waninge, A., Dekker, A.D. Dementia in people with severe/profound intellectual (and multiple) disabilities: applicability of items in dementia screening instruments for people with intellectual disabilities. Journal of Mental Health Research in Intellectual Disabilities, 2022, 15(4), 322-363. https://doi.org/10.1080/19315864.2022.2111737

Dementia in people with severe/profound intellectual (and multiple) disabilities: applicability of items in dementia screening instruments for people with intellectual disabilities

Journal article

Differentiating dementia from baseline level of functioning is difficult among people with severe/profound intellectual (and multiple) disabilities. Moreover, studies on observable dementia symptoms are scarce. This study examined (a) the relevance of dementia diagnosis, (b) observable symptoms and (c) training/ information needs.  Four explorative focus groups were held with care professionals and family members who have experience with people with severe/profound intellectual (and multiple) disabilities (≥40 years) and decline/dementia. Thematic analysis showed that participants wanted to know about a dementia diagnosis for a better understanding and to be able to make informed choices (question 1). Using a categorization matrix, cognitive and behavioral changes were shown to be most prominent (question 2). Participants indicated that they needed enhanced training, more knowledge development and translation, and supportive organizational choices/policies (question 3). Timely identifying/diagnosing dementia allows for a timely response to changing needs. This requires a better understanding of symptoms.

Source: Dekker, A.D., Wissing, M.B.G., Ulgiati, A.M., Bijl, B., van Gool, G., Groen, M.R., Grootendorst, E.S., van der Wal, I.A., Hobbelen, J.S.M., De Deyn, P.P., & Waninge, A. Dementia in people with severe or profound intellectual (and multiple) disabilities: Focus group research into relevance, symptoms and training needs. Journal of Applied Research in Intellectual Disability, 2021 Nov, 34(6), 1602-1617. https://doi.org/10.1111/jar.12912

Dementia in people with severe or profound intellectual (and multiple) disabilities: Focus group research into relevance, symptoms and training needs.

Journal article

Observable dementia symptoms are hardly studied in people with severe/profound intellectual (and multiple) disabilities (SPI(M)D). Insight in symptomatology is needed for timely signaling/diagnosis. This study aimed to identify practice-based observations of dementia symptoms in this population.
Care professionals and family members were invited to complete a survey about symptoms. Quantitatively analyzed survey data were further deepened through semi-structured interviews with care professionals having vast experience in signaling/diagnosing dementia in this population. Symptoms were categorized using a symptom matrix.  Survey respondents and interviewees frequently observed a decline in activities of daily living (ADL) functioning and behavioral and psychological changes, like increased irritability, anxiety, apathy, and decreased eating/drinking behavior. Cognitive symptoms were particularly recognized in persons with verbal communication and/or walking skills. To a lesser extent motor changes and medical comorbidities were reported. Increased insight in dementia symptoms contributes to developing a dedicated screening instrument for dementia in people with SPI(M)D.

Source:  Wissing, M.B.G., Fokkens, A.S., Dijkstra, R., Hobbelen, J.S. M.,  van der Putten, A.A.J., De Deyn, P.P., Waninge, A., & Dekker, A.D.  Dementia in people with severe/profound intellectual (and multiple) disabilities: practice-based observations of symptoms. Journal of Mental Health Research in Intellectual Disabilities, 2022, 15(4), 364-393. https://doi.org/10.1080/19315864.2022.2061092

Dementia in people with severe/profound intellectual (and multiple) disabilities: practice-based observations of symptoms

Journal article

Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Authors shrived to characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). Methods: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). Results showed that symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2 = 0.627, F(15,76) = 8.510, p < 0.001). Authors note that NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

Source:  Fonseca, L.M., Mattar, G.P., Haddad, G.G., Burduli, E., McPherson, S.M., Guilhoto, L.M., Yassuda, M.S., Busatto, G.F., Bottino, C.M., Hoexter, M.Q., & Chaytor, N.S. (2021). Neuropsychiatric Symptoms of Alzheimer’s Disease in Down Syndrome and Its Impact on Caregiver Distress. Journal of Alzheimer's Disease, 81, 137 - 154.  https://www.semanticscholar.org/paper/Neuropsychiatric-Symptoms-of-Alzheimer%E2%80%99s-Disease-in-Fonseca-Mattar/710494ac155566d9b861825cff9e8b0104b6d6a0

Neuropsychiatric symptoms of Alzheimer’s disease in Down syndrome and its impact on caregiver distress

Journal article

In people with severe or profound intellectual disabilities, it is difficult to diagnose dementia. As timely identification and diagnosis of dementia allows for a timely response to changing client wishes and needs, this study examined symptoms, and diagnosis of dementia in practice. Family members and professionals were invited to fill out  survey about symptoms and diagnosis of dementia in people with severe or profound intellectual disabilities. Results of the survey were further explored within semi-structured interviews with professionals having experience with signaling and diagnosing dementia in these people. Symptoms found in the survey and transcripts of the interviews were qualitatively analyzed, using thematic analyses based on a developed symptom-matrix. The survey was filled out completely by 14 family members and 90 professionals with different backgrounds. Results showed that behavioral changes were recognized more frequently than cognitive decline. Compared to those without dementia, epilepsy and motor decline were more present in case of dementia. Fifteen interviews (until saturation) with professionals provided an in-depth view into the symptoms, and how to identify them, again stressing behavioral alterations and to a lesser extent cognitive symptoms.

Source: Waninge, A., Wissing, M., Hobbelen, H., Fokkens, A., Dekker, A., & De Deyn, P.  Dementia in people with severe/profound intellectual disabilities. Journal of Applied Research in Intellectual Disabilities, 2021, 34(5), 1214-1215.  https://doi.org/10.1111/jar.12917

Dementia in people with severe/profound intellectual disabilities

Journal article

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The information contained in this Guide is a summary of the document Behaviour Management - A Guide to Good Practice, Managing Behavioural and Psychological Symptoms of Dementia (2012) and directed toward family caregivers.  

Source: Dementia Support Australia. https://www.dementia.com.au/resource-hub/a-guide-for-family-carers-dealing-with-behaviours-in-people-with-dementia

A Guide for Family Carer - Dealing with Behaviours in People with Dementia

Behavior guidleines

This Australian practical handbook is a reference for health staff working in settings where they will care for people with dementia and BPSD. The handbook presupposes that a person with dementia and behavioral disturbance may be viewed as ‘a difficult or disruptive person’, particularly if the clinician has little experience in this area. Although the behavior may be challenging, the person is unwell and 
requires care. The key principles for providing care are: 1. Person-centered care (emphasizing understanding the person, not the behavior or disease to be ‘‘managed’’); Multidisciplinary and multi-team care (clinical challenges requiring expertise from different health professions); and 3. Legal and ethical responsibilities (diminished capacity for consent forces health professionals to consider ethical and legal challenges).

Source: NSW Ministry of Health and the Royal Australian and New Zealand College of Psychiatrists. (May 2013). Assessment and Management of People with Behavioural and Psychological Symptoms of Dementia (BPSD).  https://www.ranzcp.org/files/resources/reports/a-handbook-for-nsw-health-clinicians-bpsd_june13_w.aspx

Assessment and Management of People with Behavioural and Psychological Symptoms of Dementia (BPSD)

Behavior guidelines

Dementia is increasingly prevalent in people with severe/profound intellectual disabilities. However, early detection and diagnosis of dementia is complex in this population. This study aimed to identify observable dementia symptoms in adults with severe/profound intellectual disabilities in available literature.
A systematic literature search was conducted in PubMed, PsycINFO and Web of Science with an exhaustive search string using a combination of search terms for severe/profound intellectual disabilities and dementia/ageing. Eleven studies met inclusion criteria. Cognitive decline, behavioral and psychological alterations, decline in activities of daily living as well as neurological and physical changes were found.  Only a very limited number of studies reported symptoms ascribed to dementia in adults with severe/profound intellectual disabilities. Given the complexity of signalling and diagnosing dementia, dedicated studies are required to unravel the natural history of dementia in this population.

Source: Wissing MBG, Ulgiati AM, Hobbelen JSM, De Deyn PP, Waninge A, Dekker AD. The neglected puzzle of dementia in people with severe/profound intellectual disabilities: A systematic literature review of observable symptoms. J Appl Res Intellect Disabil. 2022 Jan;35(1):24-45. doi: 10.1111/jar.12920. Epub 2021 Jul 4. PMID: 34219327; PMCID: PMC9292142.

The neglected puzzle of dementia in people with severe/profound intellectual disabilities: A systematic literature review of observable symptoms

Journal article

The information contained in this Australian guide is a modified summary of the document Behaviour Management - A Guide to Good Practice, Managing Behavioural and Psychological Symptoms of Dementia (2012).  This field guide provides casual points for consideration for clinicians in their role of assisting residential care staff, community care staff, and family members caring for persons living with dementia, who present with behavioral and psychological symptoms of dementia (BPSD). 

Source: Dementia Collaborative Research Centre – Assessment and Better Care (DCRC-ABC) at UNSW Australia (The University of New South Wales) 2014.  https://dementiaresearch.org.au/resources/bpsdguide/

A Clinician’s Field Guide to Good Practice Managing Behavioural and Psychological Symptoms of Dementia

Behavioral guideline

Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Objective: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). Methods: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). Results: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p  = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2  = 0.627, F(15,76) = 8.510, p  < 0.001). Conclusion: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

Source: Fonseca, L.M., Mattar, G.P., Haddad, G.G., Burduli, E., McPherson, S.M., Guilhoto, L.M., Yassuda, M.S., Busatto, G.F., Bottino, C.M., Hoexter, M.Q., Chaytor, N.S. (2021). Neuropsychiatric Symptoms of Alzheimer’s Disease in Down Syndrome and Its Impact on Caregiver Distress, Journal of Alzheimer's Disease, 81(1), 137-154 .DOI: 10.3233/JAD-201009

Neuropsychiatric symptoms of Alzheimer’s disease in Down syndrome and its impact on caregiver distress

Journal article

A review of 23 studies investigating the prevalence of behavioral and psychological symptoms of dementia (BPSD) in the general and intellectual disability population and measures used to assess BPSD was carried out. BPSD are non-cognitive symptoms, which constitute as a major component of dementia regardless of its subtype. Research has indicated that there is a high prevalence of BPSD in the general dementia population. There are limited studies, which investigate the prevalence of BPSD within individuals who have intellectual disabilities and dementia. Findings suggest BPSDs are present within individuals with intellectual disabilities and dementia. Future research should use updated tools for investigating the prevalence of BPSD within individuals with intellectual disabilities and dementia.

Source:  Devshi, R., Shaw, S., Elliott-King, J., Hogervorst, E., Hiremath, A., Velayudhan, L., Kumar, S., Baillon, S., & Bandelow, S. (2015). Prevalence of Behavioural and Psychological Symptoms of Dementia in Individuals with Learning Disabilities. Diagnostics (Basel, Switzerland), 5(4), 564–576. https://doi.org/10.3390/diagnostics5040564

Prevalence of behavioural and psychological symptoms of dementia in individuals with learning disabilities

Journal article

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