Autism, aging, and dementia: A consensus report of the Autism/Dementia Work Group of the 2nd International Summit on Intellectual Disabilities and Dementia
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
Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment
Use of antipsychotics, benzodiazepine derivatives, and dementia medication among older people with intellectual disability and/or autism spectrum disorder and dementia
Adapting Eligibility Criteria for Prescribing FDA Approved Anti-Amyloid Immunotherapeutics for Adults with Down Syndrome with Early-Stage Alzheimer’s Dementia (Statement)
Dementia in people with severe/profound intellectual (and multiple) disabilities: applicability of items in dementia screening instruments for people with intellectual disabilities
![People with Down syndrome (DS) are at high risk of developing Alzheimer dementia (DS-AD) due to a triplication of the amyloid precursor protein gene. While several tools to diagnose and screen for DS-AD, such as the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID), are available in English, validated German versions of such instruments are scarce. A German version of the DSQIID questionnaire (DSQIID-G) was completed by caregivers before attending our specialist outpatient department for DS-AD. All participants were assessed blind to DSQIID-G scoring using clinical and neuropsychological examinations, including the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). ICD-10 and amyloid/tau/ neurodegeneration (A/T/N) criteria were applied to detect and categorise cognitive decline. Of 86 participants, 43 (50%) showed evidence of cognitive decline. A definite diagnosis of DS-AD was reached in 17 (19.8%) and mild cognitive impairment in seven (8.3%) participants. Secondary causes of cognitive decline were determined among 13 (15.1%) participants, and in six (7%) cases, the diagnosis remained unclassifiable due to co-morbidities. Compared with cognitively stable individuals, participants with cognitive decline (n = 43) displayed higher DSQIID-G total scores [median (range): 3 (0-21) vs. 19 (0-48), P < 0.001]. A total score of >7 provided a sensitivity of 0.94 against a specificity of 0.76, to discriminate DS-AD and participants without cognitive decline according to ROC analysis. The convergent validity against the CAMDEX-DS interview score was good (r = 0.74), and split-half reliability (r = 0.96), internal consistency (Cronbach's α r = 0.96), test-retest reliability (r = 0.88) (n = 25) and interrater reliability (r = 0.81) (n = 31) were excellent. The DSQIID-G showed excellent psychometric properties, including concurrent and internal validity and reliability. The cut-off value for screening was lower than in the original English validation study. For a screening instrument like DSQIID-G, a lower cut-off is preferable to increase case detection.
Source: Nuebling, G., Wagemann, O., Deb, S., Wlasich, E., Loosli, S. V., Sandkühler, K., Stockbauer, A., Prix, C., & Levin, J. Validation of a German version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID-G) in Down's syndrome. Journal of Intellectual Disability Research, 2024, 68(10), 1146-1155. https://doi.org/10.1111/jir.13144](https://static.wixstatic.com/media/8c1d0a_4bc9c73e3dbe43e6a2142eaea9bdd43d~mv2.jpg/v1/fill/w_93,h_122,al_c,q_80,usm_0.66_1.00_0.01,enc_avif,quality_auto/Image-empty-state.jpg)
![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.](https://static.wixstatic.com/media/8c1d0a_7f4496678d944b8b89719d23b8d18de3~mv2.jpg/v1/fill/w_93,h_122,al_c,q_80,usm_0.66_1.00_0.01,enc_avif,quality_auto/Image-empty-state.jpg)
![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.](https://static.wixstatic.com/media/8c1d0a_d87914019ead46dab195c181dd4747a1~mv2.jpg/v1/fill/w_93,h_122,al_c,q_80,usm_0.66_1.00_0.01,enc_avif,quality_auto/Image-empty-state.jpg)
![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](https://static.wixstatic.com/media/8c1d0a_4e7f192ade5146bd9aedfda212d6aec6~mv2.jpg/v1/fill/w_93,h_122,al_c,q_80,usm_0.66_1.00_0.01,enc_avif,quality_auto/Image-empty-state.jpg)
![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.](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)
![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.](https://static.wixstatic.com/media/8c1d0a_50687e729559414391b305ba49fd7a07~mv2.jpg/v1/fill/w_93,h_122,al_c,q_80,usm_0.66_1.00_0.01,enc_avif,quality_auto/Image-empty-state.jpg)
