INS NYC 2024 Program

Poster	Poster Session 04 Program Schedule 02/15/2024 12:00 pm - 01:15 pm Room: Majestic Complex (Posters 61-120) Poster Session 04: Neuroimaging \| Neurostimulation/Neuromodulation \| Teleneuropsychology/Technology Final Abstract #115 Neuroimaging Predictors of Cognitive Resilience in the Presence of Alzheimer’s Disease Pathology McKenna Williams, SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, United States Jeremy Elman, University of California San Diego, La Jolla, United States Christine Fennema-Notestine, University of California San Diego, La Jolla, United States Tyler Bell, University of California San Diego, La Jolla, United States Shu-Ju Lin, University of California San Diego, La Jolla, United States William Kremen, University of California San Diego, La Jolla, United States Stephen Glatt, SUNY Upstate Medical University, Syracuse, United States Category: Dementia (Alzheimer's Disease) Keyword 1: cognitive reserve Keyword 2: dementia - Alzheimer's disease Keyword 3: neuroimaging: structural Objective: Structural brain measures derived from magnetic resonance imaging (MRI) are commonly used to quantify Alzheimer’s disease (AD) progression and predict future cognitive decline; however, relationships between these MRI-based measures of disease progression and cognitive performance are highly heterogeneous. Some individuals demonstrate greater cognitive resilience—the ability to maintain cognitive performance in the face of adverse brain-related changes—though the mechanisms underlying cognitive resilience remain unclear. Here, we examined whether structural characteristics of specific brain regions confer resilience cross-sectionally and/or longitudinally by moderating the relationships between established markers of AD risk (AD neuroimaging signatures, cerebrospinal fluid biomarkers) and cognitive performance. Participants and Methods: Amyloid-positive participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) GO/2/3 cohorts with relevant imaging data were included in analyses (n=160, observations=473). Imaging measures included a validated cortical thickness/hippocampal volume AD risk signature (weighted average of cortical thickness from 7 regions plus hippocampal volume) and bilateral cortical thickness in 34 regions of interest (ROIs). Linear mixed effects models tested whether each ROI moderated the relationship between markers of AD risk (AD risk signature, cerebrospinal fluid p-tau) and memory or executive functioning composite scores. Analyses controlled for age and AD signatures, in some cases, cerebrospinal fluid p-tau, to adjust for disease staging. Results: Cross-sectionally, among amyloid-positive individuals at a given level of risk, cortical thickness in 8 ROIs significantly moderated associations between the AD signature and executive function performance (ROIs: lateral occipital, inferior parietal, banks of superior temporal sulcus, isthmus cingulate, inferior and middle temporal, precuneus, posterior cingulate). Thicker cortex in these regions minimized the negative impact of thinner cortex in AD signature regions on executive function performance. No cross-sectional moderation effects were found for memory. We then created a resilience composite (average cortical thickness in the 8 ROIs) for use in longitudinal analyses. Higher baseline resilience composite scores (indicating higher cortical thickness in these regions) were associated with less decline in memory over time (p=0.029), independent of the effects of other markers of AD risk (AD signature, p-tau, age) on decline. Moreover, baseline resilience composite scores moderated the relationship between baseline p-tau and memory over time (p=0.005), such that higher baseline resilience composite scores weakened the negative longitudinal effects of p-tau, independent of the longitudinal effects of AD signatures and age. No longitudinal effects were found for executive functioning as an outcome. Conclusions: We identified 8 brain regions that appear to confer cognitive resilience both cross-sectionally and longitudinally in the face of multiple indicators of AD pathology. Among individuals at elevated risk for AD dementia (amyloid-positive individuals), thicker cortex in resilience regions may allow individuals to maintain executive function performance despite thinner cortex in AD signature regions, predicted slower decline in memory over time, and weakened the negative effects of p-tau on memory over time. Preserved executive functioning associated with cortical thickness in these ROIs may enable compensation in subsequent memory performance over time. Collectively, these findings provide insight into possible mechanisms of cognitive resilience and individual variability in cognitive trajectories associated with AD.

Poster

02/15/2024
12:00 pm - 01:15 pm
Room: Majestic Complex (Posters 61-120)

Poster Session 04: Neuroimaging | Neurostimulation/Neuromodulation | Teleneuropsychology/Technology

Final Abstract #115

Neuroimaging Predictors of Cognitive Resilience in the Presence of Alzheimer’s Disease Pathology

McKenna Williams, SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, United States
Jeremy Elman, University of California San Diego, La Jolla, United States
Christine Fennema-Notestine, University of California San Diego, La Jolla, United States
Tyler Bell, University of California San Diego, La Jolla, United States
Shu-Ju Lin, University of California San Diego, La Jolla, United States
William Kremen, University of California San Diego, La Jolla, United States
Stephen Glatt, SUNY Upstate Medical University, Syracuse, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: cognitive reserve
Keyword 2: dementia - Alzheimer's disease
Keyword 3: neuroimaging: structural

Objective:

Structural brain measures derived from magnetic resonance imaging (MRI) are commonly used to quantify Alzheimer’s disease (AD) progression and predict future cognitive decline; however, relationships between these MRI-based measures of disease progression and cognitive performance are highly heterogeneous. Some individuals demonstrate greater cognitive resilience—the ability to maintain cognitive performance in the face of adverse brain-related changes—though the mechanisms underlying cognitive resilience remain unclear. Here, we examined whether structural characteristics of specific brain regions confer resilience cross-sectionally and/or longitudinally by moderating the relationships between established markers of AD risk (AD neuroimaging signatures, cerebrospinal fluid biomarkers) and cognitive performance.

Participants and Methods:

Amyloid-positive participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) GO/2/3 cohorts with relevant imaging data were included in analyses (n=160, observations=473). Imaging measures included a validated cortical thickness/hippocampal volume AD risk signature (weighted average of cortical thickness from 7 regions plus hippocampal volume) and bilateral cortical thickness in 34 regions of interest (ROIs). Linear mixed effects models tested whether each ROI moderated the relationship between markers of AD risk (AD risk signature, cerebrospinal fluid p-tau) and memory or executive functioning composite scores. Analyses controlled for age and AD signatures, in some cases, cerebrospinal fluid p-tau, to adjust for disease staging.

Results:

Cross-sectionally, among amyloid-positive individuals at a given level of risk, cortical thickness in 8 ROIs significantly moderated associations between the AD signature and executive function performance (ROIs: lateral occipital, inferior parietal, banks of superior temporal sulcus, isthmus cingulate, inferior and middle temporal, precuneus, posterior cingulate). Thicker cortex in these regions minimized the negative impact of thinner cortex in AD signature regions on executive function performance. No cross-sectional moderation effects were found for memory. We then created a resilience composite (average cortical thickness in the 8 ROIs) for use in longitudinal analyses. Higher baseline resilience composite scores (indicating higher cortical thickness in these regions) were associated with less decline in memory over time (p=0.029), independent of the effects of other markers of AD risk (AD signature, p-tau, age) on decline. Moreover, baseline resilience composite scores moderated the relationship between baseline p-tau and memory over time (p=0.005), such that higher baseline resilience composite scores weakened the negative longitudinal effects of p-tau, independent of the longitudinal effects of AD signatures and age. No longitudinal effects were found for executive functioning as an outcome.

Conclusions:

We identified 8 brain regions that appear to confer cognitive resilience both cross-sectionally and longitudinally in the face of multiple indicators of AD pathology. Among individuals at elevated risk for AD dementia (amyloid-positive individuals), thicker cortex in resilience regions may allow individuals to maintain executive function performance despite thinner cortex in AD signature regions, predicted slower decline in memory over time, and weakened the negative effects of p-tau on memory over time. Preserved executive functioning associated with cortical thickness in these ROIs may enable compensation in subsequent memory performance over time. Collectively, these findings provide insight into possible mechanisms of cognitive resilience and individual variability in cognitive trajectories associated with AD.