Table 1. Main characteristics of the included studies.
| Study | Study design | Participants | Intervention | Outcome assessments | Main findings | ||||||||
| Sample size | Type (diagnostic criteria) | Age (M±SD) | Sex ratio (M/F) | Type of strains | Duration (weeks) | Dosage | Cognitive outcomes | Inflammatory/ oxidative biomarkers | |||||
| PRO | CON | PRO | CON | ||||||||||
| Elmira Akbari (2016) | Randomized, double-blind, controlled trial | 60 | AD (NINCDS- ADRDA criteria) | 77.67 ± 2.62 | 82.00 ± 1.69 | 6/24 | 6/24 | Multiple (Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum) | 12 | 8×109 (CFU/ g) | MMSE | TAC GSH MDA hs-CRP NO | Probiotic consumption for 12 weeks positively affected cognitive function and some metabolic statuses in the AD patients |
| Omid Reza Tamtaji (2018) | Randomized, double-blind, controlled trial | 90 | AD (NINCDS- ADRDA criteria) | 76.2 ± 8.1 | 78.8 ± 10.2 | Multiple (Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium longum) | 12 | 6×109 (CFU/ day) | MMSE | TAC GSH MDA hs-CRP NO | Probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. | ||
| Azadeh Agahi (2018) | Randomized, double-blind, controlled trial | 48 | AD (NINCDS- ADRDA criteria) | 79.70 ± 1.72 | 80.57 ± 1.79 | 7/18 | 10/13 | Multiple (Lactobacillus fermentum, Lactobacillus plantarum, Bifidobacterium lactis Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium longum) | 12 | 3×109 (CFU/ day) | TYM | TAC GSH MDA NO | Cognitive and biochemical indications in the patients with severe AD were insensitive to the probiotic supplementation. |
| Y. Kobayashi (2019) | Randomized, double-blind, controlled trial | 121 | Subjective memory complaints (MMSE, 22-27) | 61.5 ± 6.83 | 61.6 ± 6.37 | 30/31 | 30/30 | Sole (Bifidobacterium breve A1) | 12 | >2.0×1010 (CFU/ day) | MMSE | hs-CRP | No significant intergroup difference was observed in terms of changes in scores from the baseline scores |
| 44 | MCI (RBANS <41) | Sole (Bifidobacterium breve A1) | 12 | >2.0×1010 (CFU/ day) | MMSE | Significant difference between B. breve A1 and placebo groups in terms of MMSE total score in the subjects with MCI | |||||||
| Yun-Ha Hwang (2019) | Multi-center, randomized, double-blind, controlled trial | 100 | MCI (DSM-5) | 68.0 ± 5.12 | 69.2 ± 7.00 | 20/30 | 14/36 | Sole (Lactobacillus plantarum C29) | 12 | >1.0 × 1010 (CFU/ day) | VLT ACPT DST | DW2009 can be safely administered to enhance cognitive function in individuals with MCI. | |
Abbreviations: PRO, probiotics group; CON, control group; CFU, colony-forming units; AD, Alzheimer’s disease; MCI, mild cognitive impairment; NINCDS-ADRDA criteria, National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (ADRDA); MMSE, Mini-Mental State Examination; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; TAC, total anti-oxidant capacity; GSH, total glutathione; MDA, malondialdehyde; hs-CRP, high-sensitivity C-reactive protein; NO, nitric oxide; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, 5th edition; VLT, verbal learning test; ACPT, auditory continuous performance test; DST, digit span test; DW2009, Lactobacillus plantarum C29-fermented soybean.