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
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