Effects of probiotic supplements on cognition, anxiety, and physical activity in subjects with mild and moderate Alzheimer’s disease: A randomized, double-blind, and placebo-controlled study

Randomized, double-blind, placebo-controlled, multicenter trial in Iran. Older adults with mild to moderate Alzheimer's disease were assigned in a 1:1:1 ratio to Lactobacillus rhamnosus HA-114, Bifidobacterium longum R0175, or placebo.

Two oral probiotic regimens were tested for 12 weeks: Lactobacillus rhamnosus HA-114 or Bifidobacterium longum R0175. Participants took two capsules daily, one after lunch and one after dinner; each capsule was reported to contain 10^15 CFU, and the active regimens were compared with placebo.

Both probiotic strains improved cognition and anxiety over 12 weeks, with better MMSE, CFT, and IADL outcomes than placebo, but no significant benefit for basic ADL. MMSE and CFT showed significant time-by-group effects (both P < 0.0001); post hoc MMSE differences versus placebo were 4.86 for B. longum and 4.06 for L. rhamnosus, and CFT favored both active arms versus placebo (P < 0.0001). IADL also improved versus placebo for L. rhamnosus (difference 1.05, 95% CI 0.49-1.61; P < 0.0001) and B. longum (difference 1.50, 95% CI 0.93-2.06; P < 0.0001), while ADL was not significant (P = 0.24). GAD-7 decreased substantially in both groups (L. rhamnosus -6.44, 95% CI -7.77 to -5.12; B. longum -6.26, 95% CI -7.59 to -4.93; both P < 0.0001), and no serious side effects were reported.

Per-active-arm sample size was modest (n = 30 each), and follow-up was short at 12 weeks. The trial was conducted in one country and some functional outcomes did not improve, which limits certainty and generalizability.