Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study

Abstract

Cholinesterase inhibitors appear to offer benefit for people with Down syndrome and Alzheimer's disease that is comparable with sporadic Alzheimer's disease; a trial to test the effect of earlier treatment (prodromal Alzheimer's disease) in Down syndrome may be indicated. Declaration of interest A.S. has undertaken consulting for Ono Pharmaceuticals, outside the submitted work. Z.W. has received a consultancy fee and grant from GE Healthcare, outside the submitted work.

Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years

“… 27 , 28 Our data confirm some of the other associations with mortality previously observed, including the deleterious effect of epilepsy and the potentially beneficial effect of currently available medication such as acetyl-choline esterase inhibitors. 29 However, other associations were not observed: antipsychotics have been found to double mortality risk in people with dementia in the non-DS population, 30 yet in our sample we did not find a statistically significant association between antipsychotic use and death in those with or without dementia. Similarly, obesity had no discernible association with death or dementia onset in this study.…”

New approaches to studying early brain development in Down syndrome

“…Current clinical trials in adolescents and adults with Down syndrome are aimed at improving cognition and delaying progression into Alzheimer disease. Two groups of common medications used to treat the symptoms of Alzheimer disease, acetylcholinesterase inhibitors (Aricept/Donepezil, Rivastigmine) and N‐methyl‐D‐aspartate receptor antagonists (Memantine), are currently undergoing clinical trials in patients with Down syndrome . With the ultimate aim of reducing amyloid toxicity and regulating myo‐inositol levels, s cyllo ‐Inositol (ELND005) has recently also been shown to be well tolerated in a Phase II clinical trial in young adults with Down syndrome without dementia .…”

“…Two groups of common medications used to treat the symptoms of Alzheimer disease, acetylcholinesterase inhibitors (Aricept/ Donepezil, Rivastigmine) and N-methyl-D-aspartate receptor antagonists (Memantine), are currently undergoing clinical trials in patients with Down syndrome. 56,75 With the ultimate aim of reducing amyloid toxicity and regulating myo-inositol levels, scyllo-Inositol (ELND005) has recently also been shown to be well tolerated in a Phase II clinical trial in young adults with Down syndrome without dementia. 76 In addition, further novel pharmacological interventions have also been developed based on the improved knowledge of the genes located on Hsa21 and their specific pathways, including DYRK1a inhibitors (Epigallocatechin gallate), a selective gamma-Aminobutyric acid-A a5 receptor negative allosteric modulator (Basmisanil/RG1662; CLEMATIS Study), and antioxidant vitamin E. 56…”

Author's reply

“…These therapies are recommended by the National Institute for Health and Clinical Excellence for dementia treatment and the guideline includes people with Down syndrome. 1 Although subject to limitations given the observational rather than randomised design (discussed in more detail in the paper) our results support the use of antidementia drugs for people with Down syndrome who develop Alzheimer's disease. We welcome Professor Buckley's interest in our work, and she is right to highlight the complexities of medication decision-making.…”

“…As practising clinicians who provide care to adults with Down syndrome, we appreciate Eady and colleagues' attempt to address a real concern in this patient population. 1 However, we have significant concerns about clinicians potentially using in their practice the conclusions drawn by the authors. The study conclusions offer false hope and may result in wasted resources.…”