Title | FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Murray J, Tsui WH, Li Y, McHugh P, Williams S, Cummings M, Pirraglia E, Solnes L, Osorio R, Glodzik L, Vallabhajosula S, Drzezga A, Minoshima S, de Leon MJ, Mosconi L |
Journal | Adv J Mol Imaging |
Volume | 4 |
Issue | 2 |
Pagination | 15-26 |
Date Published | 2014 Apr |
ISSN | 2161-6728 |
Abstract | 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 F-FDG and the amyloid- (A) tracer C-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 A pathology in the younger cohort, suggesting that neuronal dysfunction may precede major aggregated A burden in young NL FH+. Longitudinal follow-up is required to determine if the observed abnormalities predict future AD. |
DOI | 10.4236/ami.2014.42003 |
Alternate Journal | Adv J Mol Imaging |
PubMed ID | 25530915 |
PubMed Central ID | PMC4270202 |
Grant List | R01 AG022374 / AG / NIA NIH HHS / United States R01 AG035137 / AG / NIA NIH HHS / United States R21 AG032554 / AG / NIA NIH HHS / United States R01 AG013616 / AG / NIA NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States |
Related Institute:
Brain Health Imaging Institute (BHII)