| dc.description.abstract | Enlarged perivascular spaces (ePVS) are a marker of small vessel disease that have not been well studied. The etiologies and clinical consequences of ePVS are not well studied. The objective of this project was to identify potential drivers of ePVS formation and if ePVS are predictive of worse cognition and cognitive decline.
Data comes from the Vanderbilt Memory & Aging Project (n=327, 73±7 years, 59% male), a longitudinal study of older adults undergoing serial evaluations over a 7-year period, including cardiac MRI to quantify aortic stiffening, brain MRI to quantify ePVS burden, neuropsychological assessment, and lumbar puncture to quantify markers of microglial activation and basement membrane degradation. We used a deep learning U-net to quantify basal ganglia ePVS volumes and counts at baseline and longitudinally.
Basal ganglia volumes ranged 43-1177 mm3 (237±172). Mean follow-up time was 5.2±1.7 years. Increased aortic stiffening was associated with increased baseline basal ganglia ePVS volume (b=7x10-5, p=0.04) and count (b=0.02, p=0.03). Hypertension was associated with increased baseline basal ganglia ePVS volume (b=0.0004, p=0.04) and count (b=0.14, p=0.01). Greater cerebrospinal fluid levels of sTREM2 (b=1.83x10-8, p=0.01), MMP2 (b=1.77x10-9, p=0.03), and MMP3 (b=1.81x10-7, p=0.03) were associated with longitudinal increase in basal ganglia ePVS volume. Greater ePVS volume at baseline was associated with longitudinal decline in information processing speed (b=-147, p=0.03), executive function (b=-10.9, p=0.03), and episodic memory (b=-10.6, p=0.02) performances.
We found that aortic stiffness and hypertension are predictive of worse ePVS burden at baseline. sTREM2, a marker of microglia activation, as well as MMP2 and MMP3, markers of change in the blood-brain barrier, are predictive of longitudinal increase in ePVS burden. Worse vascular health contributes to ePVS burden and outcomes appear to be worse among individuals with high levels of microglial activation and basement membrane breakdown. Worse ePVS burden was predictive of cognitive decline in domains of information processing, executive function, and episodic memory. ePVS appear to be clinically significant and should be evaluated when considering a patient’s clinical picture. ePVS highlight another avenue by which worse cardiovascular health can contribute to cognitive decline and why therapies targeting vascular health can be beneficial for the brain. | |
