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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, 2024, in press.  DOI:10.1002/alz.13778

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

Journal article

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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




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

Early-onset dementia in autism spectrum disorder

Journal article

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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

This Australian document provides guidance for clinicians in their role of assisting residential aged care facility staff, community care staff and family members caring for persons living with dementia, who present with behavioral and psychological symptoms of dementia (BPSD). A comprehensive evidence and practice-based overview of BPSD management principles provides practical strategies and interventions for assisting care staff and family carers to manage behaviors in dementia.

Behaviour Management - A Guide to Good Practice: Managing Behavioural and Psychological Symptoms of Dementia

Behavior Guidelines

This viewpoint reports on the results of the Clarity AD trial, a phase 3 randomized clinical trial of lecanemab for patients with early Alzheimer disease, in which lecanemab’s clinical efficacy was demonstrated using well-established outcome measures. Authors discuss the implications of the findings and the reported risks.  From a clinician's perspective, they comment that persons diagnosed with Alzheimer's disease should have access to this drug, although no mention is made of its safety or applicability to adults with intellectual disability. The authors note the work that still remains to be undertaken, lecanemab's success represents a major milestone for the field, and what they consider as a moment of great hope for patients and families living with Alzheimer's disease.

Source: Wolk DA, Rabinovici GD, Dickerson BC. A Step Forward in the Fight Against Dementia-Are We There Yet? JAMA Neurol. 2023 Mar 13. doi: 10.1001/jamaneurol.2023.0123. Epub ahead of print. PMID: 36912845.

A Step Forward in the Fight Against Dementia -- Are We There Yet?

Journal article

Lecanemab (Leqembi®) is a therapeutic approved in the United States for the treatment of Alzheimer’s disease (AD) to be initiated in early AD (mild cognitive impairment [MCI] due to AD or mild AD dementia) with confirmed brain amyloid pathology. Appropriate Use Recommendations (AURs) are intended to help guide the introduction of new therapies into real-world clinical practice. Adverse events may occur with lecanemab including amyloid related imaging abnormalities (ARIA) and infusion reactions. Monitoring guidelines for these events are detailed in this AUR. Most ARIA with lecanemab is asymptomatic, but a few cases are serious or, very rarely, fatal. Microhemorrhages and rare macrohemorrhages may occur in patients receiving lecanemab. Anticoagulation increases the risk of hemorrhage, and the AUR recommends that patients requiring anticoagulants not receive lecanemab until more data regarding this interaction are available. Patients who are apolipoprotein E ε4 (APOE4) gene carriers, especially APOE4 homozygotes, are at higher risk for ARIA, and the AUR recommends APOE genotyping to better inform risk discussions with patients who are lecanemab candidates. Patients and their care partners must understand the potential benefits, the potential harms, and the monitoring requirements for treatment with this agent.

“Persons with Down syndrome develop AOAD and are amyloid positive. There is an increased occurrence of CAA in patients with Down syndrome and they should be excluded from treatment with lecanemab. Clinical trials for patients with Down syndrome are under consideration and additional data including information that may guide the use of lecanemab in this population are expected.” [p. 13]

Source: Cummings, J., Apostolova, L., Rabinovici, G.D. et al. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis (2023). https://doi.org/10.14283/jpad.2023.30

Lecanemab: Appropriate Use Recommendations

Journal article

This guidebook provides guidance for the crossroads and decisions that arise in later life and at the end of life. The information covered  aims to be practical and supportive, with guidance and resources to help families, caregivers, care partners, and others. The intent is to help readers recognize and understand the 
reasons that planning for your own future and having a backup plan for care of an adult Down syndrome at the end of life, including where dementia is present.

End-of-life and Down syndrome: A companion guidebook to aging and down syndrome: A health and well-being guidebook

Resource guide

This Down Syndrome Medical Interest Group-USA updated summary covers what is known about this phenomenon and provides sections on 'what is regression?", 'what are some some of the symptoms associated with Down syndrome regression?", "How to get evaluated", "What are other causes of regression", "what test are available?", and is there a treatment?".

Regression in Persons with Down Syndrome: Current Consensus Update for Families

Resource document

This NINDS booklet is designed to help people with frontotemporal disorders and their families learn more about these conditions and resources for coping. The publication provides detailed information about the three major types of frontotemporal disorders: progressive behavior/personality decline (such as Pick's disease), progressive language decline (including primary progressive aphasia), and progressive motor decline. Common symptoms, causes, and diagnosis are discussed. Information about the treatment and management of these disorders, with practical advice for both people with frontotemporal disorders and their caregivers, is provided.

Source: Pub ID: NINDS-19-AG-6361.  NINDS. (2018). https://catalog.ninds.nih.gov/sites/default/files/publications/frontotemporal-disorders-information-patients-families-caregivers.pdf

Frontotemporal Disorders: Information for Patients, Families, and Caregivers

Resource publication

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This NINDS publication is meant to help people with Lewy body dementia, their families, and professionals learn about this disease and resources for coping. It explains what is known about the different types of Lewy body dementia and how they are diagnosed. Information about the treatment and management of this disease, with practical advice for both people with Lewy body dementia and their caregivers is provided.

Source: Pub ID: NINDS-18-AG-7907.  https://catalog.ninds.nih.gov/publications/lewy-body-dementia-information-patients-families-and-professionals

Lewy Body Dementia: Information for Patients, Families, and Professionals

Resource publication

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Adults with intellectual disability are affected by dementia at equivalent and elevated rates, many surviving into advanced age. End of life care and support considerations come into play among these individuals when most are in the advanced stage of dementia.  A preliminary report summarizing available literature and making initial recommendations was developed by a workgroup, reviewed by all conference participants and then was finalized by the workgroup. The International Summit on Intellectual Disability and Dementia produced a report on End of life care in advanced dementia that provides a synthesis statement which encompasses defining the state of advanced dementia, proposes use of palliative care services (including hospice) and recommends special efforts for enabling advanced directives and advance care planning prior to the extensive progression of dementia. The Summit further recommended that when aiding adults with advanced dementia, the following be undertaken: integrative efforts between intellectual disability and palliative care providers, specialized training for carers on end of life care and supports, and involvement of adults with intellectual disability early on in their advance care planning. The Consensus recommendations will ensure greater and more appropriate support at end of life for persons with intellectual disabilities and advanced dementia. 

Source: McCallion P, Hogan M, Santos FH, McCarron M, Service K, Stemp S, Keller S, Fortea J, Bishop K, Watchman K, Janicki MP; Working Group of the International Summit on Intellectual Disability and Dementia. Consensus statement of the International Summit on Intellectual Disability and Dementia related to end-of-life care in advanced dementia. J Appl Res Intellect Disabil. 2017 Nov;30(6):1160-1164. doi: 10.1111/jar.12349. Epub 2017 May 9.

Consensus Statement of the International Summit on Intellectual Disability and Dementia Related to End-of-life Care in Advanced Dementia

Journal article

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The International Summit on Intellectual Disability and Dementia (Glasgow, Scotland; October 2016) noted that advanced dementia can be categorized as that stage of dementia progression characterized by significant losses in cognitive and physical function, including a high probability of further deterioration and leading to death. The question before the Summit was whether there were similarities and differences in expressions of advanced dementia between adults with intellectual disability (ID) and adults in the general population. The Summit noted challenges in the staging of advanced dementia in people with ID with the criteria in measures designed to stage dementia in the general population heavily weighted on notable impairment in activities of daily living. For many people with an ID, there is already dependence in these domains generally related to the individuals pre-existing level of intellectual impairment, that is, totally unrelated to dementia. Hence, the Summit agreed that as was true in achieving diagnosis, it is also imperative in determining advanced dementia that change is measured from the person's prior functioning in combination with clinical impressions of continuing and marked decline and of increasing co-morbidity, including particular attention to late-onset epilepsy in people with Down syndrome. It was further noted that quality care planning must recognize the greater likelihood of physical symptoms, co-morbidities, immobility and neuropathological deterioration.  The Summit recommended an investment in research to more clearly identify measures of person-specific additional decline for ascertaining advanced dementia, inform practice guidelines to aid clinicians and service providers and identify specific markers that signal such additional decline and progression into advanced dementia among people with various levels of pre-existing intellectual impairment. 

Source: McCarron M, McCallion P, Coppus A, Fortea J, Stemp S, Janicki M, Wtachman K. Supporting advanced dementia in people with Down syndrome and other intellectual disability: consensus statement of the International Summit on Intellectual Disability and Dementia. J Intellect Disabil Res. 2018 Jul;62(7):617-624. doi: 10.1111/jir.12500. Epub 2018 May 20.

Supporting Advanced Dementia in People with Down Syndrome and Other Intellectual Disability: Consensus Statement of the International Summit on Intellectual Disability and Dementia

Journal article

Post diagnostic support (PDS) has varied definitions within mainstream dementia services and different health and social care organizations, encompassing a range of supports that are offered to adults once diagnosed with dementia until death. An international summit on intellectual disability and dementia held in Glasgow, Scotland in 2016 identified how PDS applies to adults with an intellectual disability and dementia. The Summit proposed a model that encompassed seven focal areas: post-diagnostic counseling; psychological and medical surveillance; periodic reviews and adjustments to the dementia care plan; early identification of behaviour and psychological symptoms; reviews of care practices and supports for advanced dementia and end of life; supports to carers/ support staff; and evaluation of quality of life. It also explored current practices in providing PDS in intellectual disability services. The Summit concluded that although there is limited research evidence for pharmacological or non-pharmacological interventions for people with intellectual disability and dementia, viable resources and guidelines describe practical approaches drawn from clinical practice. Post diagnostic support is essential, and the model components in place for the general population, and proposed here for use within the intellectual disability field, need to be individualized and adapted to the person's needs as dementia progresses. Recommendations for future research include examining the prevalence and nature of behavioral and psychological symptoms (BPSD) in adults with an intellectual disability who develop dementia, the effectiveness of different non-pharmacological interventions, the interaction between pharmacological and non-pharmacological interventions, and the utility of different models of support. 

Source: Dodd K, Watchman K, Janicki MP, Coppus A, Gaertner C, Fortea J, Santos FH, Keller SM, Strydom A. Consensus statement of the international summit on intellectual disability and Dementia related to post-diagnostic support. Aging Ment Health. 2018 Nov;22(11):1406-1415. doi: 10.1080/13607863.2017.1373065. Epub 2017 Sep 7.

Consensus Statement of the International Summit on Intellectual Disability and Dementia Related to Post-Diagnostic Support

Journal article

Biogen's notice on 8/4/21 offered as an educational resource for healthcare providers in response to an unsolicited request by Dr. Seth Keller, co-President of the NTG. The notice indicated that aducanumab-avwa has not been studied in persons with Down Syndrome associated Alzheimer’s disease (DS AD), and there there are no data on the efficacy and safety in this population. The notice cites the work of Cummings et al (2021) which acknowledges as that there are many differences between Down syndrome and late onset AD and as such, it is recommended against treating persons with Down syndrome with aducanumab-avwa until more data are available. According to Cummings et al., persons with Down syndrome may eventually become eligible for treatment after additional studies have been conducted and additional data are accrued for this group of individuals. It also cites various sources, including the NTG, recommending the generation of more applicability and use protocols.

Biogen commentary on Aduhelm and Down syndrome

Report

Aducanumab is an amyloid-targeting monoclonal antibody delivered by monthly intravenous infusions. The pivotal trials included patients with early AD (mild cognitive impairment due to AD and mild AD dementia) who had confirmed brain amyloid using amyloid positron tomography. As clinicians require guidance on the appropriate use of this new therapy, an Expert Panel was assembled to construct Appropriate Use Recommendations based on the participant populations, conduct of the pivotal trials of aducanumab, updated Prescribing Information, and expert consensus. 

The Expert Panel recommended that use of aducanumab be restricted to this population in which efficacy and safety have been studied. As aducanumab is titrated to a dose of 10 mg/kg over a 6-month period, the Expert Panel recommended that the aducanumab be titrated to the highest dose to maximize the opportunity for efficacy. Given that aducanumab can substantially increase the incidence of amyloid-related imaging abnormalities (ARIA) with brain effusion or hemorrhage, dose interruption or treatment discontinuation is recommended for symptomatic ARIA and for moderate-severe ARIA. The Expert Panel recommended the use of MRIs prior to initiating therapy, during the titration of the drug, and at any time the patient has symptoms suggestive of ARIA. The Expert Panel also recommended that measures less cumbersome than those used in trials be used for the assessment of effectiveness in the practice setting.
 
The Expert Panel emphasized the critical importance of engaging in a process of patient-centered informed decision-making that includes comprehensive discussions and clear communication with the patient and care partner regarding the requirements for therapy, the expected outcome of therapy, potential risks and side effects, and the required safety monitoring, as well as uncertainties regarding individual responses and benefits.

Source: Cummings J, Aisen P, Apostolova LG, Atri A, Salloway S, Weiner M. Aducanumab: Appropriate Use Recommendations. J Prev Alzheimers Dis. 2021;8(4):398-410. doi: 10.14283/jpad.2021.41.

Aducanumab: Appropriate Use Recommendations

Journal article

This recently updated second edition of Mental Wellness in Adults with Down Syndrome reflects both the breadth of the authors' knowledge - acquired as co-founders of the first medical clinic dedicated solely to the care of adults with Down syndrome - and the number of psychosocial issues and mental disorders that can affect people with Down syndrome. It is a 'go-to' guide for parents, health practitioners, and caregivers who support teens and adults with Down syndrome.  Its focus is on mental wellness and the understanding and appreciation that both the strengths and challenges of people with Down syndrome are the key to promoting good mental health.  Readers will learn to distinguish between bona fide mental health issues and common characteristics of Down syndrome  and whether these are quirks or coping strategies. For example, although talking to oneself can be a sign of psychosis, many adults with Down syndrome use self-talk as an effective problem-solving strategy.  The second edition includes new chapters on sensory issues and regression, chapters on communication, concrete thinking, and visual memory, and an extensively updated chapter on Alzheimer's disease citing new research. Other chapters cover a range of conditions and assessment and treatment options.  
Source: Dennis McGuire, PhD & Brian Chicoine, MD, (2021), Woodbine House Publishing (with 2nd Ed. rights for self-publish reverted to the authors), 588pp.

Mental Wellness in Adults with Down Syndrome: A Guide to Emotional and Behavioral Strengths and Challenges (2nd Ed.)

Book

Book chapter from McGuire & Chicoine [Mental Wellness in Adults with Down Syndrome: A Guide to Emotional and Behavioral Strengths and Challenges (2nd Edition), 2021] addressing a phenomenon where teens or young adults with Down syndrome experienced a puzzling decline in abilities. These individuals, usually in their twenties or younger, suddenly lost speech, cognitive, and daily living skills and often had 
behavioral or psychological changes. This “regression” has people with Down syndrome experiencing a puzzling decline in abilities and is reported to occur following a period of stable functional skill acquisition in young adolescents or adults as described by their families.

Regression (Down Syndrome)

Book chapter

Abstract:  Down syndrome (DS) lacks a suitable outcome measure for prevention trials targeting pre-dementia stages.  Authors used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time and then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria and the panel found that there were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted of memory, language/executive functioning, selective attention, orientation, and praxis tests.  The authors have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer’s disease

Journal Article

This document, released on February 21, 2023, was issued jointly by the NTG and the Health Matters Program as part of an advisory series on risk reduction in adults with intellectual disability and promoting healthy brain outcomes. The advisory recognizes that in some instances overmedicating can have negative effects on physical and brain health, as well as potentially increase the risk for mild cognitive impairment or dementia. The intent of the advisory is that the information provided will lead to constructive scrutiny of medication use, avoid “medication harm’, and result in positive health outcomes.

Over-Medication and Older Adults with Intellectual Disability: Risks for Brain Health (Statement)

NTG Statement

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