Preventive Effect of Rifampicin on Alzheimer Disease Needs at Least 450 mg Daily for 1 Year: An FDG-PET Follow-Up Study

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Therapeutic role of rifampicin in Alzheimer's disease

“…Furthermore, pilot clinical studies indicate that patients with AD may benefit from rifampicin treatment. Despite these positive study results, clinical confirmatory evidence remains scarce and results are inconsistent . To overcome the above‐mentioned barriers to consistent clinical data, well‐designed randomized clinical research with larger experimental pharmacological combination studies is needed.…”

“…Despite these positive study results, clinical confirmatory evidence remains scarce and results are inconsistent. [61][62][63][64][65][66][67] To overcome the above-mentioned barriers to consistent clinical data, well-designed randomized clinical research with larger experimental pharmacological combination studies is needed. This approach should also be combined with prospective functional neuroimaging data (etc., amyloid-PET) and clinical assessment scores.…”

“…In line with this, Iizuka et al described that preventive effect of rifampicin needs at least 450 mg daily for 1 year even during the pre-dementia stage. 67 In their interesting retrospective FDG-PET study, rifampicin therapy in the predementia stage significantly improved the metabolic (posterior cingulate gyrus) and cognitive decline in the long-term follow up. Rifampicin dose and treatment (450 mg/ day for ≥12 months) significantly improved the FDG uptake in the posterior cingulate gyrus, which was reflected in Mini-Mental State Examination scores.…”

“…In line with this, Iizuka et al . described that preventive effect of rifampicin needs at least 450 mg daily for 1 year even during the pre‐dementia stage . In their interesting retrospective FDG‐PET study, rifampicin therapy in the predementia stage significantly improved the metabolic (posterior cingulate gyrus) and cognitive decline in the long‐term follow up.…”

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

“…Noteworthy is the fact that an anti-mycobacterial antibiotic, rifampicin, inhibits the pathology of AD in an animal model [162]. Moreover, rifampicin was found to have preventative effects on preclinical and prodromal AD patients [163].…”