. Amyloid-s burden and neuropsychological test performance in cognitively normal first-degree relatives at varying genetic risk for Alzheimer's disease. Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;


In Alzheimer's disease (AD) there is strong evidence that brain amyloid deposition precedes the emergence of dementia by many years. In addition, a greater accumulation of amyloid in the postmortem brain has been demonstrated in people who carry the major genetic risk factor for AD.APOE-e4. This study investigated the relationship between APOE-e4 genotype, amyloid deposition, and neuropsychological test performance in presymptomatic individuals at varying genetic risk for AD.

Methods: Cognitively normal subjects aged 50-69 with a first-degree family history for AD were genetically screened to select three groups: APOE genotype e4e4 (n = 14), e3e4 (n = 14), and e3e3 (n = 14), matched for age and sex. Subjects were then studied with ([11C]PiB) PET, MRI, and neuropsychological testing. PET and MR images were co-registered for application of an ROI template (AAL for SPM2) to generate regional time-activity curves with cerebellum as reference region. Parametric BPND images were then generated using SRTM2 such that BPND = 0 reflected no specific binding. BPND was computed for a mean cortical ROI consisting of frontal, posterior cingulateprecuneus, lateral parietal, and lateral temporal ROIs.

Results: APOE-e4 carriers demonstrated significantly greater BPND (0.17}0.19) in comparison to non-carriers (0.04}0.09; F = 6.35, p = 0.016, ANCOVA controlling for age and sex), with no dosage effect between e4e4 (0.19}0.13) and e3e4 (0.15}0.23) groups. There was no significant effect of APOE genotype on neuropsychological test performance. There were also no significant associations between mean cortical [11C]PiB BPND and neuropsychological test performance in the overall sample, although some tendency was observed for an association with performance on the Boston Naming Test (r = -0.34, p = 0.03).

Conclusions: These results corroborate and extend observations by Reiman et al (2009) but with a somewhat reduced APOE-e4 effect in a younger sample (mean age 59 vs 65). Neuropsychological test results confirm the full cognitive gnormalityh of many at risk subjects with considerable fibrillar amyloid burden.


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  1. Miami: HAI Amyloid Imaging Conference Abstracts