Exploration of Neuroprotective Therapy

Table 2. Key clinical studies investigating the cognitive and biological effects of probiotics in Alzheimer’s disease and mild cognitive impairment.

Study (author, year)	Study design	Population	Probiotic intervention	Duration	Key cognitive outcomes	Biomarker/other outcomes
Akbari et al. [3], 2016	RCT	60 AD patients	Lactobacillus acidophilus, L. casei, Bifidobacterium bifidum, L. fermentum (2 × 10⁹ CFU each)	12 weeks	MMSE ↑ 27.9% vs. ↓ 5.03% in controls	hs-CRP ↓ 17.6%, MDA ↓ 22%
Akhgarjand et al. [40], 2022	RCT	70 mild-to-moderate AD patients	L. rhamnosus HA-114 or B. longum R0175 (10¹⁵ CFU)	12 weeks	MMSE ↑ by 4.86 points, IADLs improved	No significant change in basic ADLs
Hsu et al. [41], 2024	RCT	Number not specified (AD patients)	Multi-strain probiotics including Lactobacillus and Bifidobacterium species (5 × 10⁷–1 × 10¹⁰ CFU)	12 weeks	Trend toward reduced cognitive decline	IL-1β ↓, SOD ↑, BDNF ↑ by 36%
Den et al. [42], 2020	Systematic review and meta-analysis	297 AD/MCI patients	Various probiotic interventions across studies	Varied	Significant cognitive improvement (SMD = 0.37, p = 0.002)	Reduction in inflammation (SMD = –0.57)
Liu et al. [56], 2020	Systematic review and meta-analysis	386 AD patients	Various probiotic formulations	Varied	Improved cognitive function, memory, daily functioning	Not specified

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RCT: randomized controlled trial; AD: Alzheimer’s disease; CFU: colony-forming units; MMSE: mini-mental state examination; hs-CRP: high-sensitivity C-reactive protein; MDA: malondialdehyde; IADLs: instrumental activities of daily living; IL-1β: interleukin-1 beta; SOD: superoxide dismutase; BDNF: brain-derived neurotrophic factor; MCI: mild cognitive impairment; SMD: standardized mean difference.

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AAS: Conceptualization, Investigation, Data curation, Writing—original draft. HSW: Conceptualization, Supervision, Writing—review & editing, Methodology. AP: Investigation, Writing—original draft, Writing—review & editing. ST: Data curation, Writing—review & editing. BS: Data curation, Writing—review & editing. NN: Investigation, Writing—review & editing. All authors read and approved the submitted version.

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The authors declare that they have no conflicts of interest.

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