<b><i>Background:</i></b> Rifampicin was reported to inhibit amyloid-β oligomerization and tau hyperphosphorylation in mouse models and could serve as a promising available medicine for the prevention of Alzheimer disease (AD). To examine whether rifampicin has such preventive effects in humans, we retrospectively reviewed ¹⁸F-FDG-PET findings of elderly patients with mycobacterium infection treated with rifampicin. <b><i>Methods:</i></b> Forty nondemented elderly patients treated with rifampicin for mycobacterium infections who showed AD-type hypometabolism were enrolled. The hypometabolic patterns were evaluated with stereotaxic statistical analysis and region of interest analysis. <b><i>Results:</i></b> Before treatment, AD-type hypometa bolism was observed in 12 patients. The FDG uptake in the posterior cingulate cortex (PCC) was improved or stabilized in 6 patients after 12-month therapy (450 mg/day), whereas another 6 patients with 6-month therapy showed a decreased FDG uptake in the PCC. In patients who underwent FDG-PET only after treatment, the metabolic decline in the PCC was significantly milder in patients with ≥12 months of rifampicin treatment than in those with 6 months of treatment. Multiple regression analysis revealed that the dose of rifampicin and treatment duration significantly influenced FDG uptake in the PCC. <b><i>Conclusion:</i></b> The preventive effect of rifampicin depended on the dose and the treatment duration, and the effect needs at least 450 mg daily for 1 year.