A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease

To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD).

Randomized, triple-blind, controlled trial.

Three tertiary care and two community geriatric clinics in Canada.

One hundred one patients with probable AD and mild to moderate dementia.

Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months.

The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status.

There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups.

Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.