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
Supporting Advanced Dementia in People with Down Syndrome and Other Intellectual Disability: Consensus Statement of the International Summit on Intellectual Disability and Dementia
![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_90,h_122,al_c,q_80,usm_0.66_1.00_0.01,blur_3,enc_auto/Image-empty-state.jpg)
![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.](https://static.wixstatic.com/media/8c1d0a_e31a11296bbe44e2974b99e148cbdc66~mv2.jpg/v1/fill/w_90,h_122,al_c,q_80,usm_0.66_1.00_0.01,blur_3,enc_auto/Image-empty-state.jpg)
![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,blur_3,enc_auto/Image-empty-state.jpg)
![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](https://static.wixstatic.com/media/8c1d0a_581e504da09a4bb3b3483ca2b4086a41~mv2.jpg/v1/fill/w_93,h_121,al_c,q_80,usm_0.66_1.00_0.01,blur_3,enc_auto/Image-empty-state.jpg)
![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.](https://static.wixstatic.com/media/8c1d0a_dfb62b22ac4f404a90870992612c9de7~mv2.jpg/v1/fill/w_93,h_112,al_c,q_80,usm_0.66_1.00_0.01,blur_3,enc_auto/Image-empty-state.jpg)
