Alex Casem
Research Mentor: Alexandru Iordan
Mentor Department: Research Program on Cognition and Neuromodulation Based Interventions, Medicine
Author(s): Alex Casem, Quentin Devignes, Patrick Pruitt, Alexandru Iordan, Benjamin Hempstead
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Oral Presentation
Abstract
Introduction: White matter (WM) lesions are common findings in aging and Alzheimer’s disease (AD) and are thought to reflect underlying vascular dysfunction and damage to white matter pathways. Vascular stress biomarkers such as placental growth factor (PlGF) may indicate endothelial dysfunction and vascular pathology that contribute to these brain changes. Elevated levels of PIGF have been reported in AD, vascular dementia, and other neurodegenerative disorders, which suggests a potential role as a biomarker of vascular-related brain pathology. WM lesion burden has been associated with cognitive decline, particularly in memory, in older adults. However, few studies have examined how vascular stress biomarkers, WM lesions, and memory relate to one another within the same sample, a gap that is addressed in the present study. Methods: We enrolled 180 older adults (mean age: 72.2 ± 7.0 years; 45.6% female) with amnestic mild cognitive impairment (aMCI; N = 111) and mild-to-moderate dementia of Alzheimer’s type (DAT; N = 69). Participants completed neuropsychological testing and 3T MRI scanning, including high-resolution T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences used to estimate white matter hyperintensities (WMH) volume. WMH volume was divided by the total WM volume to adjust for interindividual differences in brain size. Blood samples were also collected to measure plasma placental growth factor (PlGF), a biomarker associated with vascular stress. To adjust for skewness, both WMH volume and PlGF levels were log10-transformed. Memory performance was assessed using two cognitive tests, namely the Benson Complex Figure test and the Craft Story 21 test. We created a delayed memory composite score by averaging z-scores from each test. We used linear regression models to investigate the relationships between (1) WMH volume and levels of plasma PlGF, (2) WMH volume and delayed memory composite score, and (3) levels of plasma PlGF and delayed memory composite score. All analyses controlled for age, sex, and education. Significance threshold was set at p < .05. Results: There was no significant association between WMH volume and levels of plasma PlGF (b = -0.060; t = -0.159; p =0 .874). There was also no significant association between WMH volume and delayed memory composite score (b = -0.006; t = -0.374; p = .709).. Finally, we did not find a significant association between levels of plasma PlGF and delayed memory composite score(b = -0.137; t = -0.208; p = .836). Conclusions: Our findings show that plasma PlGF levels were not significantly associated with WMH volume or delayed memory performance, and WMH burden was also not significantly related to memory in this sample. Although previous studies have linked WMH and vascular biomarkers to cognitive decline, our results suggest that these relationships may not always be directly observable in individuals who already have memory impairment. For future work, we may explore other vascular stress biomarkers and methods for measuring and quantifying WM integrity to better understand how vascular changes in the brain relate to cognitive performance.
