[18F]Fluorodeoxyglucose (FDG) Imaging of Pre-Manifest Huntington’s Disease:Analysis by CAP Score

419 Objectives: Huntington’s Disease (HD) is an autosomal-dominant neurodegenerative disease characterized by progressive movement and cognitive abnormalities. The underlying genetic mutation is an unstable expanded DNA trinucleotide (cytosine-adenosine-guanine [CAG]) repeat within the coding region for the protein huntingtin on chromosome 4. The number of CAG repeats has been found to be inversely related to the age of onset of motor symptoms and therefore, clinical diagnosis. The cumulative toxicity of the abnormal huntingtin protein has been estimated by the CAG-Age Product (CAP score = Age x (CAG - 33.66)). Objectives: To examine relationships between regional glucose metabolic rates (SUV) and genetic risk (CAP score) in a sample of pre-manifest HD participants. Methods: Thirty-nine (13 M, 26 F, 19 - 81 years of age (43.0 ± 12.9 years)) premanifest HD participants (CAG repeat length 38 - 52 (mean = 42.7 ± 3.2) were imaged with FDG. Participants had a CAP score = 359 ± 77 (range: 220 - 542, low = 7, medium = 14, high = 18) at the time of imaging. Co-registered FDG and T1-weighted images were processed (NEURO tool, PMOD, v. 3.7) to generate cortical and subcortical volumes-of-interest (VOI, N = 78 regions) specific for the individual participant. SUVs were generated for each VOI as well as partial-volume-corrected (PVC) values based on the geometric transfer matrix (GTM) method. Volume-weighted global SUVs were calculated. Analyses employed VOI parameterized in SUV units and as globally-normalized and globally-normalized partial-volume-corrected (PVC) SUV values (i.e., SUVVOI/SUVglobal). Results: Hypometabolism was evident in the caudate and/or putamen in 25/39 pre-manifest HD participants (low = 2/7, medium = 8/14, high = 15/18). Metabolism in the bilateral caudates and putamen (SUV, normalized SUV, PVC normalized SUV) were negatively correlated (Pearson’s and Spearman’s) with the CAP score at the time of imaging. No other regions were consistently related to the CAP score across parameterizations. Conclusions: Pre-manifest HD patients show reduced FDG uptake in bilateral caudate and putamen that correlates with the cumulative toxicity estimated by the CAP score.