# Intraindividual cognitive variability in aging adults with Down syndrome: associations with Alzheimer's disease plasma biomarkers, neuropathology and clinical dementia

> **NIH NIH K99** · WASHINGTON STATE UNIVERSITY · 2024 · $128,589

## Abstract

PROJECT SUMMARY/ABSTRACT
Individuals with Down syndrome (DS) are at higher risk for developing Alzheimer’s disease (AD) compared to
the general population. As such, they are considered an ideal target population for anti-AD therapy trials;
however, there is no reliable measure for predicting dementia onset in this population. Intraindividual cognitive
variability (IICV), a measure of variability in neuropsychological test performance within a person at a single
timepoint, is a novel, low-cost, non-invasive biomarker of neurodegeneration and early dementia for the general
population. However, IICV has not been investigated in adults with DS. Therefore, the current proposal will fill
this knowledge gap by characterizing the associations between IICV, AD biomarkers, and dementia in adults
with DS. Aims 1 and 2 of this proposal use data from the Alzheimer’s Biomarker Consortium-Down Syndrome
(ABC-DS) study, which is currently composed of cognitive and biomarker data collected at two different
timepoints (baseline and 18 months), to calculate IICV measures for memory, executive function and processing
speed, visuospatial construction, and multidomain cognition in 300 adults with DS. Using the longitudinal ABC-
DS data, we will first examine whether IICV is associated with AD plasma biomarkers (β-amyloid 42/40, p-
tau217, and NfL) and/or AD-related pathology (Aβ-PET and tau-PET) (K99, Aim 1). We will also examine
whether IICV is associated with the clinical presentation of dementia and cognitive decline (K99, Aim 2).
We expect our analyses to show that IICV is positively associated with AD-related biomarkers and pathology,
and that IICV at baseline is associated with a follow-up diagnosis of dementia as well as cognitive decline from
baseline to follow-up. These data will be critical for optimizing the design of a new cohort study of adults with DS
that will test the outcome measures from Aims 1 and 2 in a new, more diverse, cross-cultural cohort of
adults with DS from Washington State and São Paulo, Brazil, and include comparisons with a control
group of individuals with autosomal dominant AD, due to its similarity with DS in early striatal amyloid-
β deposition (R00, Aim 3). To complete these aims, we have developed a comprehensive, mentored training
plan for me to (1) gain expertise in the relationship between neuropsychology, plasma biomarkers and
neuroimaging; (2) broaden my knowledge of the similarities and differences between autosomal dominant AD
and AD in DS; (3) explore cross-cultural similarities and differences in AD risk; and (4) develop advanced
statistical skills. The data and training obtained in the K99 phase will lead to the successful implementation of a
high-quality, international research program focused on IICV and AD biomarkers in DS. Findings have great
potential to be used with the DS population worldwide, increasing the chances of early interventions and inclusion
in anti-AD trials. The intense training in the K99 and the supp...

## Key facts

- **NIH application ID:** 10900616
- **Project number:** 5K99AG082864-02
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Luciana Fonseca
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $128,589
- **Award type:** 5
- **Project period:** 2023-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900616

## Citation

> US National Institutes of Health, RePORTER application 10900616, Intraindividual cognitive variability in aging adults with Down syndrome: associations with Alzheimer's disease plasma biomarkers, neuropathology and clinical dementia (5K99AG082864-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10900616. Licensed CC0.

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