Annika Nissen
Research Mentor: Alexandru Iordan
Mentor Department: Research Program on Cognition and Neuromodulation Based Interventions, Medicine
Author(s): Annika Nissen, Quentin Devignes, Patrick Pruitt, Benjamin Hampstead , Alexandru Iordan
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 129
Abstract
Background: Alzheimer’s disease (AD) pathological processes include amyloid-beta (Aß) plaque buildup, neurofibrillary tangles of hyperphosphorylated tau proteins, and neurodegeneration, especially in the medial temporal lobe (MTL). Clinically, AD is characterized by progressive memory loss. This study examined whether regional Aß and tau burden are differentially associated with MTL structural integrity and delayed memory performance in older adults on the symptomatic AD spectrum. Methods: 203 older adults on the symptomatic AD spectrum (amnestic MCI and mild AD dementia) enrolled in the STIM study (PI: Hampstead) completed neuropsychological assessments, Aß and tau PET scans, and a 3T MRI scan. We used the high-resolution T1-weighted MRI sequence to segment MTL regions, namely the hippocampus, amygdala, parahippocampal cortex (PHC), and entorhinal cortex (ERC). Mean Aß and tau DVR values were extracted for the same anatomically defined MTL regions of interest, yielding region-matched PET and MRI measures for each participant. We created an episodic memory composite score derived from standardized delayed recall measures for verbal (Craft Story 21 test) and visuospatial (Benson Complex Figure test) memory tests. For each bilateral MTL region, we used multiple linear regression to test associations among regional volume, regional Aß and tau DVR, and delayed memory performance, adjusting for age, sex, and education. Models including regional volumes also controlled for total intracranial volume. Regional Aß and tau DVRs were entered simultaneously in the regression models to estimate their independent associations. We used a significance threshold adjusted using the Bonferroni method of 0.004 (0.05/12 models). Results: Higher regional tau DVR, but not Aß DVR, was significantly associated with smaller volume for all examined MTL regions (all p-values<0.001). Lower volumes of hippocampus, amygdala, and ERC were significantly associated with lower episodic memory composite score (all p-values<0.001). Greater regional tau DVR in all MTL regions were significantly associated with lower episodic memory composite score (all p-values<0.002), while greater regional Aß DVR in the PHC only was associated with lower episodic memory composite score (p-value<0.001). Conclusions: Regional tau burden showed stronger independent associations than Aß burden with MTL atrophy and memory performance. Regional volume of all MTL regions was also associated with worse memory performance. These findings are consistent with the view that tau is more proximally related than Aß to structural degeneration and memory impairment in symptomatic AD.
