Neuropsychiatric Symptom Emergence in Down Syndrome-Associated Alzheimer's Disease is Associated With Tau but not Amyloid Accumulation.

Authors

Jason K Russell, Paul A Newhouse, Michael S Rafii, Jo Ellen Wilson, Alzheimer’s Biomarker Consortium – Down Syndrome

Published in

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. Sep 25, 2026. Epub Sep 25, 2026.

Abstract

To identify the emergence of behavioral symptoms in adults with Down syndrome (DS) in association with Alzheimer's disease (AD) pathology or cognitive performance.
We investigated the prevalence and severity of behavioral symptoms across age, and the longitudinal emergence of positive and negative symptoms in participants who were cognitively stable. We applied linear mixed effects models to assess the relationship between behavioral symptoms and AD pathology or cognitive performance.
Ten University sites in the United States and United Kingdom.
About 336 participants with Down syndrome from the Alzheimer's Biomarker Consortium-Down Syndrome cohort study.
Positive (increased or additional abnormal behaviors) and negative (absence of normal behavior or motivation) symptomatology as composites from subdomain scores on the Reiss Screen for Maladaptive Behavior and the Dementia Questionnaire for People with Learning Disabilities, amyloid accumulation in centiloids, regional tau accumulation, regional cortical thickness, and cognitive performance on the modified Cued Recall Test (mCRT) and Down Syndrome Mental Status Exam.
Individuals with DS display a high prevalence of behavioral symptomatology across adulthood. Individuals who are cognitively stable, with low levels of behavioral symptomatology had increased odds of developing positive (OR = 1.51, CI = 1.30-1.75, p <0.0001) and negative symptoms (OR = 1.42, CI = 1.28-1.58, p <0.0001) yearly. Positive symptom severity associated with tau accumulation in the entorhinal cortex (β = 1.74, p = 0.0227) and lateral occipital cortex (β = 3.15, p <0.0001) and negative symptom severity with mCRT performance (β = -0.192, p = 0.0432).
Measurable changes in behavioral symptomatology emerge in adults with DS with no previous behavioral symptoms as AD pathology develops and cognition declines.

PMID:
42919767
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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