Generational effects in Down syndrome: Enriched environment enhances functionality without reducing Alzheimer's disease risk

Abstract

Introduction: Down syndrome (DS) is the leading cause of intellectual disability (ID) and a genetic form of Alzheimer's disease (AD). We wanted to assess whether generational changes have induced (1) milder ID with greater independence and (2) delayed AD diagnosis.

Methods: We analyzed 681 asymptomatic DS to test generational effects on ID, functionality, and cognition. In 353 DS individuals with AD, we compared clinical diagnosis age by ID using analysis of variance. In addition, dementia diagnosis age was examined through a published meta-analysis.

Results: Our results indicate a generational shift toward a higher proportion of individuals with mild/moderate ID, greater intelligence, and autonomy. However, it was not paralleled by an ID-related delay in the age at AD onset in our cohort, or by generational delays reported over the past 35 years.

Discussion: The findings highlight notable generational improvements in DS, but no effects on the age at AD dementia diagnosis.

Highlights: A generational effect has reduced the severity of intellectual disability in Down syndrome (DS). Individuals with DS have increased autonomy and improved intellectual milestones. The enriched environment has not delayed the age at Alzheimer's disease (AD) dementia in DS. Further studies should confirm if cognitive reserve might delay AD in DS.

Keywords: Alzheimer's disease (AD); Down syndrome (DS); functionality; intellectual disability (ID); intelligence.