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FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer’s Disease

Advances in Molecular Imaging 2014年第2期4卷 15-26页

作者： John Murray Wai H. Tsui Yi Li Pauline McHugh Schantel Williams Megan Cummings elizabeth pirraglia Lilja Solnes Ricardo Osorio Lidia Glodzik Shankar Vallabhajosula Alexander Drzezga Satoshi Minoshima Mony J. de Leon Lisa Mosconi New York University School of Medicine New York USA University of Cologne Cologne Germany University of Washington Seattle USA Weill Cornell Medical College New York USA

Having a parent affected by late-onset Alzheimer’s disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with 18F-FDG and the amyloid-β (Aβ) tracer 11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents. Methods: FDG- and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD (FH+) and 39 NL with negative family history of any dementia (FH-). The FH+ group included 50 subjects with maternal (FHm) and 30 with paternal family history (FHp). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative (+/-) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y). Results: Among individuals of age >60 y, as compared to controls, NL FH+ showed a higher frequency of FDG+ scans vs. FH- (53% vs. 6% p < 0.003), and a trend for PiB+ scans (27% vs. 11%;p = 0.19). This effect was observed for both FHm and FHp groups. Among individuals of age ≤60 y, NL FHm showed a higher frequency of FDG+ scans (29%) compared to FH- (5%, p = 0.04) and a trend compared to FHp (11%) (p = 0.07), while the distribution of PiB+ scans was not different between groups. In both age cohorts, FDG+ scans were more frequent than PiB+ scans among NL FH+, especially FHm (p < 0.03). FDG-PET was a significant predictor of FH+ status. Classification according to PiB status was significantly less successful. Conclusions: Automated analysis of FDG- and PiB-PET demonstrates higher rates of abnormalities in at-risk FH+ vs FH-subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of Aβ pathology in the younger cohort, suggesting that neuronal dysfunction may

关键词： Alzheimer’s Disease Early Detection Positron Emission Tomography Amyloid Imaging Glucose Metabolism Normal Aging

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