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

Abstract

Probiotics have been suggested as an effective adjuvant treatment for Alzheimer’s disease (AD) due to their modulating effect on the gut microbiota, which may affect the gut-brain axis. Therefore, we aimed to evaluate the effects of two different single-strain probiotics on cognition, physical activity, and anxiety in subjects with mild and moderate AD. Eligible patients (n = 90) with AD were randomly assigned to either of two interventions [Lactobacillus rhamnosus HA-114 (1015 CFU) or Bifidobacterium longum R0175 (1015 CFU)] or placebo group, receiving probiotic supplement twice daily for 12 weeks. The primary outcome of the study was cognitive function measured by using the two tests, namely, the Mini-Mental State Examination (MMSE) and the categorical verbal fluency test (CFT). Secondary outcomes included a performance in Activities of Daily Living (ADL), the Lawton Instrumental Activities of Daily Living (IADL) scale, and the Generalized Anxiety Disorder (GAD-7) scale. Linear mixed-effect models were used to investigate the independent effects of probiotics on clinical outcomes. After 12 weeks, MMSE significantly improved cognition (PInteraction < 0.0001), with post hoc comparisons identifying significantly more improvement in the B. longum intervention group (differences: 4.86, 95% CI: 3.91–5.81; P < 0.0001) compared with both the placebo and L. rhamnosus intervention groups (differences: 4.06, 95% CI: 3.11–5.01; P < 0.0001). There was no significant difference between the two intervention groups (differences: −0.8, 95% CI: −1.74 to 0.14; P = 0.09). In conclusion, this trial demonstrated that 12-week probiotic supplementation compared with placebo had beneficial effects on the cognition status of patients with AD.

Exploring the Influence of Gut–Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics

“…The average follow-up period across these studies was 12 weeks. One study involved patients receiving a probiotic fermented dairy beverage at a dosage of 2 mL/kg/day [ 37 ], while three other studies administered the probiotic in capsule form, with a dosage of twice 10 15 CFU/day [ 37 , 38 , 39 , 40 ]. Additionally, one study included selenium supplementation at a dose of 200 μg/day [ 40 ].…”

“…Ton AMM et al’s study [ 37 ] provided an initial assessment of the positive impacts of kefir supplementation over 90 days on cognitive function, along with the biomarkers associated with systemic oxidative stress, inflammation, and cell damage in elderly individuals with Alzheimer’s disease. Akhgarjand et al’s trial [ 38 ], focusing on probiotic supplementation’s influence on cognitive status in patients with mild and moderate Alzheimer’s disease, demonstrated a noteworthy enhancement in MMSE total score. Moreover, improvements were observed in the categorical verbal fluency test (CFT), Activities of Daily Living (AD), and Generalized Anxiety Disorder (GAD-7) in response to probiotic supplementation.…”

Mapping new pharmacological interventions for cognitive function in Alzheimer’s disease: a systematic review of randomized clinical trials

“…The response to nutritional interventions is greater in the early stages of AD ( Moreira et al, 2020 ), and this response is linked to the APOE genotype ( Xu et al, 2020 ). The maximum benefit of probiotics has been observed in individuals with early cognitive dysfunction and no effect has been found in those with advanced disease or no apparent disease ( Akhgarjand et al, 2022 ; Sánchez-De-Lara-Sánchez and Sánchez-Pérez, 2022 ). Caprylic acid is a ketone that, when metabolized, produces beta-hydroxybutyrate and acetoacetate ketones, that can cross the blood-brain barrier.…”

Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential

“…This finding aligns with the conclusion reached by Asaoka et al [ 120 ]. The MMSE and categorical verbal fluency test scores were much higher after a 12-week course of treatment with Bifidobacterium longum R0175 and Lactobacillus rhamnosus HA-114, and AD-related symptoms were dramatically reduced in AD patients [ 121 ]. Furthermore, the administration of combined probiotics, namely Bifidobacterium longum BORI BGN4 and Bifidobacterium bifidum , effectively mitigated the psychological stress in elderly individuals and substantially elevated the expression levels of BDNF.…”