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IC‐P‐118: Validated Dementia Risk Measure is Associated With Regional Brain Volumes: The ANU Alzheimer’s Disease Risk Index (ANU‐ADRI)
Author(s) -
Cherbuin Nicolas,
Shaw Marnie,
Sachdev Perminder S.,
Anstey Kaarin J.
Publication year - 2016
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.2016.06.148
Subject(s) - dementia , neuroimaging , medicine , psychology , disease , neuroscience
10 years before any symptoms develop. A new marker of neurodegeneration, increased CSF visinin-like protein 1 (VILIP-1), may predict cognitive decline and has been shown to be increased in carriers of an ADAD mutation. We wanted to further characterize in ADAD this new marker of neurodegeneration by evaluating its relationship with well-known AD biomarkers, in particular FDG hypometabolism, which is believed to reflect neuronal dysfunction and injury. Methods:Participants from the Dominantly Inherited Alzheimer Network (DIAN) study (n1⁄4202, including 124 mutation carriers [MC], 43 of whom were symptomatic) underwent MRI, PiB and FDG PET scans and CSF VILIP-1 measurement. Dementia severity was defined by the Clinical Dementia Rating (CDR). The cohort was divided by mutation status (non-carriers [NC] vs. MC) and b-amyloid status (PiB-negative vs. PiB-positive) for group comparisons. The standardized uptake value ratio (SUVR) of PiB and FDG, obtained from an MRI-based PET processing method, were corrected and normalized to the brainstem. Partial correlations between PET SUVR data and CSF-VILIP-1 levels controlling for age and family history were performed. Results: This study confirmed increased CSF VILIP-1 levels and decreased FDG SUVR values inMC compared to NC. Among carriers, PiB-positive participants had higher VILIP-1 levels compared to PiB-negative (p<0.005). VILIP-1 trended higher in PiB-positive asymptomatic participants compared to PiB-negative (p1⁄40.07). A positive correlation between mean cortical PiB SUVR and VILIP-1 (r1⁄40.36, p<0.0001) and a negative correlation between FDG PET in the precuneus and VILIP-1 in all participants (r1⁄4-0.33, p<0.0001) were observed. The negative correlation between CSF-VILIP-1 and FDG PET was driven by the PiB-positve MC participants. Conclusions: These preliminary results show that increased CSF VILIP-1, a marker of neuronal injury, is associated with both abnormal amyloid deposition and cerebral glucose hypometabolism in the DIAN population. Longitudinal investigation and evaluation of other AD features are still needed. Support: NIH/NIA U01AG032438.