Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome

Abstract

This meta-analysis assesses whether the variability in symptom onset of Alzheimer disease in Down syndrome is similar to autosomal dominant Alzheimer disease and its association with mortality.

Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome

“…Our findings have several implications for public health and clinical practice. Although the risk of developing dementia before the age of 40 years is low, 31 cognitive decline (once practice effects are accounted for) starts earlier in individuals with DS (10-15 years before the median diagnosis of prodromal AD), 6 , 7 in agreement with previous work 32 , 33 , 34 showing that longitudinal AD-related cognitive decline starts in the fourth decade in people with DS. This temporality of cognitive decline is similar to that described in ADAD, starting with episodic memory decline in the preclinical stage.…”

“…The risk for progression along the AD continuum is very similar to that described in ADAD, now estimated in both populations to be more than 95% in longitudinal studies. 2 , 5 , 7 Data from general population in sporadic AD are more variable, especially because of the study setting and selection criteria (eg, population-based vs convenience cohorts and different mean ages) and different definitions of progression. Petersen 28 reported an overall annual progression from mild cognitive impairment to AD of 8% to 15% when biomarkers are not evaluated.…”

“… 1 In adults with DS, Alzheimer disease (AD) is the main medical problem and main cause of death. 2 Indeed, the AD pathological hallmarks are universal by age 40 years, 3 and the dementia prevalence increases exponentially thereafter, 4 , 5 , 6 , 7 with a cumulative incidence of more than 95% in the seventh decade. This is mainly owing to the presence of an extra copy of the amyloid-β precursor protein gene, which is coded in chromosome 21.…”

Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease

“…Down syndrome (DS) or trisomy 21 is the most common autosomal aneuploidy in human births, and it is the single most common genetic cause of intellectual disability of ∼50 years, individuals with full triplication of chromosome 21 develop Alzheimer's disease (AD) dementia (Holland et al, 1998;Margallo-Lana et al, 2007;Zigman, 2013;Covelli et al, 2016;Fortea et al, 2021;Iulita et al, 2022) with an incidence of 88-100% in those older than 65 years (McCarron et al, 2017). The development of AD in DS could be associated with an overexpression of several genes located on chromosome 21, including the amyloid precursor protein (APP) gene, which encodes the amyloid-beta precursor protein (AβPP) (Wiseman et al, 2015), leading to an increase in Aβ production.…”

“…In addition to the physiological manifestations of premature aging, people with DS present early cognitive impairment characterized by a decrease in memory skills (Godfrey and Lee, 2018 ), language skills (Vicari et al, 1994 ), social communication, motor skills, personal life, and community life skills (Hawkins et al, 2003 ). By the age of ~50 years, individuals with full triplication of chromosome 21 develop Alzheimer's disease (AD) dementia (Holland et al, 1998 ; Margallo-Lana et al, 2007 ; Zigman, 2013 ; Covelli et al, 2016 ; Fortea et al, 2021 ; Iulita et al, 2022 ) with an incidence of 88–100% in those older than 65 years (McCarron et al, 2017 ). The development of AD in DS could be associated with an overexpression of several genes located on chromosome 21, including the amyloid precursor protein ( APP) gene, which encodes the amyloid-beta precursor protein (AβPP) (Wiseman et al, 2015 ), leading to an increase in Aβ production.…”