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O2‐13‐03: REGIONAL DISTRIBUTION OF WHITE MATTER HYPERINTENSITIES RELATED TO ALZHEIMER'S DISEASE RISK FACTORS IN THE ALFA COHORT
Author(s) -
Salvadó Gemma,
Brugulat-Serrat Anna,
Sudre Carole H.,
Grau Oriol,
Falcon Carles,
Cardoso M. Jorge,
Barkhof Frederik,
Molinuevo José Luis,
Gispert Juan Domingo
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2714
Subject(s) - hyperintensity , cardiology , medicine , depression (economics) , apolipoprotein e , cohort , family history , white matter , risk factor , psychology , disease , magnetic resonance imaging , radiology , economics , macroeconomics
Background: Vascular endothelial growth factor (VEGF), the primary regulator of angiogenesis, is upregulated to enhance oxygen and glucose delivery to nutrient-deficient tissue. Amyloid disrupts VEGF signaling and may result in VEGF upregulation. This effect may explain why human studies invivo have found discrepant relationships between VEGF levels and Alzheimer’s Disease (AD) diagnosis. We hypothesize that in individuals with high amyloid (Ab+), higher CSF VEGF levels will partially compensate for Ab effects on the brain, and therefore be associated with better aging outcomes: 1) a thicker cortex, 2) greater regional FDG-PET signal, and 3) better cognitive function. Methods:We evaluated 310 participants (92 cognitively intact, 149 mild cognitive impairment, 69 AD) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Separately in Ab+ (CSF Ab 192 pg/ ml) and Abparticipants, we used multiple linear regression (controlling for age, sex, education, APOE4 carrier status, CSF T-tau, and diagnosis) to relate CSF VEGF levels to: 1) MRIderived cortical thickness in mean bilateral AD-relevant regions-of-interest (ROIs), grouping regions by their shared variances (Figure 1); 2) mean bilateral temporal lobe glucose metabolism (FDG-PET); and 3) established neuropsychological composite measures (executive function including language measures, and memory). False discovery rate (FDR) was applied to correct for multiple comparisons. We evaluated the direct and indirect effect of VEGF on executive function and memory through causal mediation analysis using the package mediation 4.4.6 in R (percentile bootstrap, B1⁄41000). Results:In Ab+ participants only, higher CSF VEGF levels were significantly associated with a thicker temporal cortex (FDR-adjusted VEGF partial p1⁄40.009, omnibus p<0.001), higher temporal lobe FDG-PET signal (VEGF partial p1⁄40.007, omnibus p<0.001), and better executive function, driven largely by category naming