APOE-specific Cognitive Effects of Levetiracetam in Mid-Age Adults
Lancaster, C.; Dowell, N. G.; Tertikas, G.; Bakker, A.; Bird, C. M.; Tabet, N.; Rusted, J.
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Background: Low-dose levetiracetam is under investigation as a potential treatment for slowing Alzheimer's Disease progression. This study tests whether levetiracetam enhances executive function in mid-age adults, and whether drug effects differ by Apolipoprotein e4 (APOE4+) genetic risk status. Methods: Fifty-eight adults (aged 45-65 years; 27 APOE33; 31 APOE4+) participated in a double-blind, placebo-controlled study of low-dose levetiracetam (125mg bidaily for two-weeks). At the end of each treatment phase, participants completed a switch-inhibition task. Results: Mid-age APOE4+ carriers were significantly slower and showed a greater cost of increasing executive demand than APOE33 individuals. Response times were quicker under levetiracetam, with increased benefits reported in APOE33 individuals, at younger ages, and in individuals with reduced levels of plasma-based biomarkers. Levetiracetam selectively benefitted accuracy in APOE33 individuals. Conclusion: Low-dose levetiracetam enhances executive function in midlife, particularly in individuals at lower risk of Alzheimer's Disease based on age, APOE4 genotype, and proxies of neuropathology.
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