White matter hyperintensity volume modifies the association between CSF vascular inflammatory biomarkers and regional FDG-PET along the Alzheimer’s disease continuum

• Published in: Neurobiology of aging Vol. 132; pp. 1 - 12
• Main Authors: Tubi, Meral A., Wheeler, Koral, Matsiyevskiy, Elizabeth, Hapenney, Matthew, Mack, Wendy J., Chui, Helena C., King, Kevin, Thompson, Paul M., Braskie, Meredith N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2023
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Biomarkers - cerebrospinal fluid; Brain - metabolism; C-Reactive Protein; Cognitive Dysfunction - metabolism; CRP; Fluorodeoxyglucose F18 - metabolism; Glucose metabolism; Humans; Inflammation - metabolism; Magnetic Resonance Imaging; Positron-Emission Tomography - methods; Vascular Endothelial Growth Factor A - metabolism; Vascular territories; VEGF; White Matter - pathology; White matter hyperintensities; CRP; FDG-PET; White matter hyperintensities; AD; vWF; CI; VEGF; MNI; MCA; ROI; PCA; CDR; Aβ; VCAM; Glucose metabolism; MCI; WMH; FDR; CSF; SUVR; APOE; ACA; Vascular territories
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2023.08.002

In older adults with abnormal levels of Alzheimer’s disease neuropathology, lower cerebrospinal fluid (CSF) vascular endothelial growth factor (VEGF) levels are associated with lower [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) signal, but whether this association is (1) specific to VEGF or broadly driven by vascular inflammation, or (2) modified by vascular risk (e.g., white matter hyperintensities [WMHs]) remains unknown. To address this and build upon our past work, we evaluated whether 5 CSF vascular inflammation biomarkers (vascular cell adhesion molecule 1, VEGF, C-reactive protein, fibrinogen, and von Willebrand factor)—previously associated with CSF amyloid levels—were related to FDG-PET signal and whether WMH volume modified these associations in 158 Alzheimer’s Disease Neuroimaging Initiative participants (55–90 years old, 39 cognitively normal, 80 mild cognitive impairment, 39 Alzheimer’s disease). We defined regions both by cortical boundary and by the 3 major vascular territories: anterior, middle, and posterior cerebral arteries. We found that WMH volume had interactive effects with CSF biomarkers (VEGF and C-reactive protein) on FDG-PET throughout the cortex in both vascular territories and conventionally defined regions of interest.