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Randomized Controlled Trial
. 2022;88(1):75-95.
doi: 10.3233/JAD-220148.

Effect of Probiotic Bifidobacterium breve in Improving Cognitive Function and Preventing Brain Atrophy in Older Patients with Suspected Mild Cognitive Impairment: Results of a 24-Week Randomized, Double-Blind, Placebo-Controlled Trial

Daisuke Asaoka  1 , Jinzhong Xiao  2   3 , Tsutomu Takeda  1 , Naotake Yanagisawa  4 , Takahiro Yamazaki  5 , Yoichiro Matsubara  5 , Hideki Sugiyama  5 , Noemi Endo  5 , Motoyuki Higa  5 , Koji Kasanuki  5 , Yosuke Ichimiya  5 , Shigeo Koido  6 , Kazuya Ohno  3 , Francois Bernier  3 , Noriko Katsumata  2   3 , Akihito Nagahara  7 , Heii Arai  8 , Toshifumi Ohkusa  2   6 , Nobuhiro Sato  2
Affiliations
Randomized Controlled Trial

Effect of Probiotic Bifidobacterium breve in Improving Cognitive Function and Preventing Brain Atrophy in Older Patients with Suspected Mild Cognitive Impairment: Results of a 24-Week Randomized, Double-Blind, Placebo-Controlled Trial

Daisuke Asaoka et al. J Alzheimers Dis. 2022.

Abstract

Background: Probiotics have been reported to ameliorate cognitive impairment.

Objective: We investigated the effect of the probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI).

Methods: In this RCT, 130 patients aged from 65 to 88 years old with suspected MCI received once daily either probiotic (B. breve MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog and MMSE tests. Participants underwent MRI to determine brain atrophy changes using Voxel-based Specific Regional Analysis System for Alzheimer's disease (VSRAD). Fecal samples were collected for the analysis of gut microbiota composition.

Results: Analysis was performed on 115 participants as the full analysis set (probiotic 55, placebo 60). ADAS-Jcog subscale "orientation" was significantly improved compared to placebo at 24 weeks. MMSE subscales "orientation in time" and "writing" were significantly improved compared to placebo in the lower baseline MMSE (< 25) subgroup at 24 weeks. VSRAD scores worsened in the placebo group; probiotic supplementation tended to suppress the progression, in particular among those subjects with progressed brain atrophy (VOI Z-score ≥1.0). There were no marked changes in the overall composition of the gut microbiota by the probiotic supplementation.

Conclusion: Improvement of cognitive function was observed on some subscales scores only likely due to the lower sensitiveness of these tests for MCI subjects. Probiotics consumption for 24 weeks suppressed brain atrophy progression, suggesting that B. breve MCC1274 helps prevent cognitive impairment of MCI subjects.

Keywords: Bifidobacterium; brain atrophy; cognitive function; mild cognitive impairment; probiotics.

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Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/22-0148r1).

Figures

Fig. 1
Fig. 1
Trial profile.
Fig. 2
Fig. 2
Change of MMSE (A to C) and change of mMMSE (D to E) from 0 to 24 weeks. A and D show data from the full analysis set. B and E for participants with baseline MMSE < 25, and C and F for participants with baseline MMSE≥25. Modified MMSE (mMMSE) are calculated by abstracting Serial-7 from the eleven items of MMSE. Filled circle (MCC1274), open circle (placebo). †p < 0.1, *p < 0.05, significant difference from Placebo group (Wilcoxon rank-sum test).
Fig. 3
Fig. 3
Subgroup analysis of gut microbiota composition by baseline MMSE scores.
Fig. 4
Fig. 4
Gut microbiota profiles by Bray-Curtis PCoA based on the genus level composition between groups and before and after the sample intake of Bifidobacterium breve MCC1274 or placebo. Open triangle: Placebo group at baseline; Open circle: Probiotic group at baseline; Filled triangle: Placebo group after intervention; Filled circle: Probiotic group after intervention.
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