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 18F-FDG and the amyloid- β (Aβ) tracer 11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents.MethodsFDG− 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).ResultsAmong 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.ConclusionsAutomated 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 precede major aggregated Aβ burden in young NL FH+. Longitudinal follow-up is required to determine if the observed abnormalities predict future AD.
Highlights
Alzheimer’s disease (AD), the leading cause of dementia in the elderly, is a neurodegenerative disorder with insidious onset and progressive cognitive declines
Among individuals of age
Observer-independent Z scoring software, the present study shows that FDG− and PiB-PET abnormalities are detectable on an individual basis in NL individuals at known increased risk for AD, years prior to possible symptoms onset
Summary
Alzheimer’s disease (AD), the leading cause of dementia in the elderly, is a neurodegenerative disorder with insidious onset and progressive cognitive declines. Many clinical studies indicate that by the time patients come in for diagnosis, too much irreversible brain damage may have already occurred for treatments to be effective. Preventive interventions, once they are developed, ideally would be implemented long before symptoms occur. Of relevance to the early detection of AD, characteristic abnormalities of both biomarkers have been observed years prior to clinical decline in asymptomatic, cognitively normal (NL) individuals [9]-[12]. Examination of at-risk individuals represents an ideal way to explore the value of these two imaging modalities in the early detection of AD-typical pathology, prior to cognitive decline
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