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

BACKGROUND: There is little evidence to guide pharmacological treatment in adults with Down syndrome and Alzheimer's disease. Aims To investigate the effect of cholinesterase inhibitors or memantine on survival and function in adults with Down syndrome and Alzheimer's disease. METHOD: This was a naturalistic longitudinal follow-up of a clinical cohort of 310 people with Down syndrome diagnosed with Alzheimer's disease collected from specialist community services in England. RESULTS: Median survival time (5.59 years, 95% CI 4.67-6.67) for those on medication (n = 145, mainly cholinesterase inhibitors) was significantly greater than for those not prescribed medication (n = 165) (3.45 years, 95% CI 2.91-4.13, log-rank test P<0.001). Sequential assessments demonstrated an early effect in maintaining cognitive function. CONCLUSIONS: 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.

Predictors of Age of Diagnosis and Survival of Alzheimer's Disease in Down Syndrome.

BACKGROUND: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer's disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade. OBJECTIVE: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these. METHODS: Data was obtained from the Aging with Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting of data extracted from clinical records of patients seen by Community Intellectual Disability Services (CIDS) in England. Survival times when considering different risk factors were calculated. RESULTS: The mean age of diagnosis was 55.80 years, SD 6.29. Median survival time after diagnosis was 3.78 years, and median age at death was approximately 60 years. Survival time was associated with age of diagnosis, severity of intellectual disability, living status, anti-dementia medication status, and history of epilepsy. Age at diagnosis and treatment status remained predictive of survival time following adjustment. CONCLUSION: This study provides the best estimate of survival in dementia within the DS population to date, and is in keeping with previous estimates from smaller studies in the DS population. This study provides important estimates and insights into possible predictors of survival and age of diagnosis of AD in adults with DS, which will inform selection of participants for treatment trials in the future.

Dementia diagnostic criteria in Down syndrome.

OBJECTIVE: Dementia is a common clinical presentation among older adults with Down syndrome. The presentation of dementia in Down syndrome differs compared with typical Alzheimer's disease. The performance of manualised dementia criteria in the International Classification of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) is uncertain in this population.We aimed to determine the concurrent validity and reliability of clinicians' diagnoses of dementia against ICD-10 and DSM-IV-TR diagnoses. Validity of clinical diagnoses were also explored by establishing the stability of diagnoses over time. METHODS: We used clinical data from memory assessments of 85 people with Down syndrome, of whom 64 (75.3%) had a diagnosis of dementia. The cases of dementia were presented to expert raters who rated the case as dementia or no dementia using ICD-10 and DSM-IV-TR criteria and their own clinical judgement. RESULTS: We found that clinician's judgement corresponded best with clinically diagnosed cases of dementia, identifying 84.4% cases of clinically diagnosed dementia at the time of diagnosis. ICD-10 criteria identified 70.3% cases, and DSM-IV-TR criteria identified 56.3% cases at the time of clinically diagnosed dementia. Over time, the proportion of cases meeting ICD-10 or DSM-IV-TR diagnoses increased, suggesting that experienced clinicians used their clinical knowledge of dementia presentation in Down syndrome to diagnose the disorder at an earlier stage than would have been possible had they relied on the classic description contained in the diagnostic systems. CONCLUSIONS: Clinical diagnosis of dementia in Down syndrome is valid and reliable and can be used as the standard against which new criteria such as the DSM-5 are measured.

Older adults with intellectual disability.

PURPOSE OF REVIEW: Improvements in health and social care for people with intellectual disability have led to a dramatic increase in the life expectancy of this population, resulting in a large and growing number of older adults with intellectual disability. They are at risk of age-related mental disorders such as dementia and continue to present with high rates of mental illness. RECENT FINDINGS: Recent research with older adults with intellectual disability has included physical health issues that may affect mental well being, and biological and clinical features of dementia in people with Down syndrome. Two key clinical trials of memantine and antioxidants for dementia in Down syndrome showed that these treatment options were ineffective in the short term. Other research focussed on environmental and psychosocial issues (including carer issues) and end-of-life care. SUMMARY: Improved mental well being requires effective management of mental illness and co-morbid physical health problems as well as consideration of environmental and social issues. Biological research has identified potential treatments for age-related decline, which has led to the development of medication trials. Despite disappointing results, two recent medication trials showed that randomized controlled trials are feasible in older people with intellectual disabilities - a group who are often excluded from trials.