Cognitive decline and dementia in Down syndrome

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Abstract

Purpose of review

Alzheimer's disease is most likely universal in older individuals with Down syndrome, due to having three copies of the amyloid precursor protein gene, resulting in amyloid-beta plaque deposition. Down syndrome is an important population in which to consider clinical trials of treatments to prevent or delay the development of dementia. However, assessment of subtler cognitive changes is challenging due to the presence of intellectual disability.

Recent findings

Recent research confirmed that older adults with Down syndrome often present with cognitive decline: more than 80% may experience dementia by age 65 years. Efforts have been made to improve and validate neuropsychological assessment and to describe the relationship with comorbidities such as epilepsy and haemorrhagic stroke. There have also been advances in biomarkers such as neuroimaging using amyloid PET.

Summary

Clinical trials of treatments, particularly in the presymptomatic phase of Alzheimer's disease, are important to consider in individuals with Down syndrome given their high dementia burden, and may also serve as proof of concept for other forms of Alzheimer's disease. However, further work is required to improve outcome measures and better understand the biomarkers of progression of disorder and their relationship with symptom development during the presymptomatic period.

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