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

Abstract

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.

Aging related cognitive changes associated with Alzheimer's disease in Down syndrome

“…[2][3][4] AD neuropathology is universally present in adults with DS from their fourth decade, 5,6 driving an elevated risk for dementia due to AD that is estimated to reach 80% by age 65, 7 though the age of clinical dementia onset shows large variability. 8 The age of onset for dementia in DS is similar to that in familial AD due to mutations in the known AD causing genes -APP, presenilin 1 (PSEN1) and presenilin 2 (PSEN2), 9 with mean age of diagnosis around 55, and an interquartile range of approximately 50-59 years of age. 8 However, unlike familial AD, the sequence and course of dementia in DS is less well-described, despite this population currently accounting for the majority of genetic AD cases.…”

“…8 The age of onset for dementia in DS is similar to that in familial AD due to mutations in the known AD causing genes -APP, presenilin 1 (PSEN1) and presenilin 2 (PSEN2), 9 with mean age of diagnosis around 55, and an interquartile range of approximately 50-59 years of age. 8 However, unlike familial AD, the sequence and course of dementia in DS is less well-described, despite this population currently accounting for the majority of genetic AD cases.…”

Self‐inflicted human bite followed by hand necrotizing fasciitis in an adult with Down syndrome

“…Alzheimer's disease has prevalence rates of 0%‐10%, 10%‐25%, 28%‐55%, and 30%‐75% in Down syndrome patients in their thirties, forties, fifties, and sixties, respectively . The duration of survival in these patients is reportedly affected by factors including the age at diagnosis of the mental illness, level of severity of the intellectual disability, living status, use of antidementia medication, and history of epilepsy . Moreover, Down syndrome is known to be associated with defective neutrophil chemotaxis, low humoral immune responses, zinc deficiency, and accelerated immunosenescence .…”

“…2 The duration of survival in these patients is reportedly affected by factors including the age at diagnosis of the mental illness, level of severity of the intellectual disability, living status, use of antidementia medication, and history of epilepsy. 5 Moreover, Down syndrome is known to be associated with defective neutrophil chemotaxis, low humoral immune responses, zinc deficiency, and accelerated immunosenescence. 6 These physiological and psychological disorders, along with intrinsic defects of the immune system, can result in various wound-related complications, such as a late recognition of newly sustained injuries, prolonged wound-healing, and chronic wound infections, in adults with Down syndrome.…”

Cognitive Changes associated with Alzheimer’s disease in Down syndrome

“…DS is also a genetic cause of Alzheimer's disease (AD), largely due to triplication of the amyloid precursor protein (APP) gene at 21q21.3 2 . AD neuropathology is universally present in adults with DS from their fourth decade 3,4 , driving an elevated risk for dementia due to AD that is estimated to reach 80% by age 65 5 , though the age of clinical dementia onset shows large variability 6 . The age of onset for dementia in DS is similar to that in familial AD due to mutations in the known AD causing genes -APP, presenilin 1 (PSEN1) and presenilin 2 (PSEN2) 7 , with mean age of diagnosis around 55, and an interquartile range of approximately 50 -59 years of age 6 .…”