Longitudinal associations of intra-individual cognitive variability with dementia, cognitive change and PET amyloid-ß in adults with Down syndrome - poster presentation

Sep 30, 2026

Uploaded by Damian

Background: Individuals with Down syndrome (DS) are an important target for anti-amyloid therapy because Alzheimer’s disease amyloid-β pathology is common, yet not all develop dementia. Intra-individual cognitive variability (IICV) may signal pre-clinical change, but evidence in DS is limited. Using ABC-DS data, relationships were assessed between baseline IICV and dementia status, cognitive decline, and brain amyloid-β measured by PET. Methods: 460 adults (25–81 years) with baseline and ~40-month follow-up received complete neuropsychological testing and consensus dementia diagnosis, with centiloid PET measures. IICV for memory, executive function, and combined domains was computed, and regression models evaluated baseline IICV associations with dementia, clinical worsening, cognitive decline, and PET amyloid-β, adjusting for covariates and using Bonferroni correction.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Background

Methods

Results

Conclusion

DOI: 10. 1002/alz70856_107396 BIOMARKERS POSTER PRESENTATION BIOMARKERS (NON-NEUROIMAGING) Longitudinal associations of intra-individual cognitive variability with dementia, cognitive change and PET amyloid-ß in adults with Down syndrome: data from the Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS) Luciana Mascarenhas Fonseca1 Naomi Sage Chaytor2 Michal S Beeri3 Eardi Lila4 Ali Shojaie4 Jasmeer P. Chhatwal5, 6 Orestes Vicente Forlenza7 Elizabeth Head8 Mark Mapstone8 Ann D Cohen9 Bradley T Christian 10 Benjamin L Handen 11 Beau Ances 12 Thomas J Grabowski4 Shahid Zaman 13 1Washington State University, Spokane, WA, USA 2 Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA 3 Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center at Rutgers Brain Health Institute, New Brunswick, NJ, USA 4 University of Washington, Seattle, WA, USA 5 Brigham and Women’s Hospital, Boston, MA, USA 6 Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 7 University of Sao Paulo, Sao Paulo, SP, Brazil 8 University of California, Irvine, Irvine, CA, USA 9 Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA 10Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA 11 University of Pittsburgh, Pittsburgh, PA, USA 12Washington University in St. Louis School of Medicine, St. Louis, MO, USA 13 University of Cambridge, Cambridge, United Kingdom Correspondence Luciana Mascarenhas Fonseca, Washington State University, Spokane, WA, USA. Email: [luciana.fonseca@wsu.edu](luciana.fonseca@wsu.edu) Abstract Background: Because of the high incidence of Alzheimer’s disease (AD) amyloid-b pathology in individuals with Down syndrome (DS), they are considered an ideal target population for anti-amyloid therapy trials. However, not all individuals with DS develop dementia. Intra-individual cognitive variability (IICV) is proposed to be a sensitive marker for pre-clinical changes in AD, but has not yet been tested in individuals with DS. Using the ABC-DS (Alzheimer’s Biomarker Consortium-DS) data, we characterize the relationships between baseline IICV with dementia status, cognitive decline and brain amyloid-b (using positron emission tomography (PET)) in adults with DS. Methods: Data from the ABC-DS study, includes 460 adults with DS ranging from 25 to 81 years of age (mean age 43.27, 45.7% female) at baseline and mean followup of 40 months (standard deviation of 7.8 months). All participants had complete neuropsychological evaluations at baseline and follow up, and consensus dementia diagnosis and brain PET amyloid-b measures in centiloids. IICV measures for memory, executive function and combined memory and executive functions were calculated. Regression models were used to examine the associations between baseline IICV scores with dementia at follow up, clinical presentation worsening from baseline to follow up, more than one standard deviation below the mean change in general cognition considering the level of intellectual disability, as well as PET amyloid-b at baseline and follow up, adjusting for age, sex, intellectual disability, site, presence of This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e107396. [https://doi.org/10.1002/alz70856_107396](https://doi.org/10.1002/alz70856_107396) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of2 BIOMARKERS APOEe4 and time latency between baseline and follow up. We adjusted for multiple comparisons using Bonferroni correction. Results: IICV for memory

FAQs

What is the main goal of this poster?

To determine whether baseline intra-individual cognitive variability (IICV) predicts dementia status, cognitive decline, and PET amyloid-β outcomes in adults with Down syndrome using ABC-DS data.

How many participants and what follow-up period were used?

The analysis included 460 adults with Down syndrome aged 25–81 years at baseline, with a mean follow-up of 40 months.

What were the key findings about IICV and dementia-related outcomes?

IICV for memory and executive functions was associated with all tested outcomes, except PET amyloid-β at follow-up, and the associations with dementia at follow-up remained after additional adjustment for cognitive performance.

Sep 30, 2026

Uploaded by Damian