Table 5.
Methodological issues of randomized controlled trials (RCT) studies about probiotic, prebiotic, and synbiotic intervention on cognition function.
| Intervention | Cognitive Impairment |
Control Group | Study Group | Cognitive Function Assessment/Diagnosis |
Microbiome Assessment | Other Assessed Parameters | Country [References] |
||
|---|---|---|---|---|---|---|---|---|---|
| N | Age | N | Age | ||||||
| PROBIOTICS | |||||||||
|
L. casei Shirota 65 mL milk drink 6.5 × 109 CFU 3 wk. |
healthy | 66 | 61.8 | 66 | 61.8 | Memory (Wechsler Memory Scale) Retrieval from long-term memory Verbal fluency |
no | eating-associated behaviour NART |
UK [91] |
|
L. helveticus-fermented milk drink 190 g/day 8 wk. |
healthy | 29 | 57.8 ± 5.9 | 31 | 58.5 ± 6.5 | RBANS | no | POMS | Japan [92] |
|
L. helveticus-fermented milk 500 mg, 1000 mg, 200 mg 12 wk. |
healthy | 10 | 64.5 ±4.8 | 10 7 9 |
64.5 ± 2.2 64.4 ± 4.5 66.6 ± 5.0 |
neuropsychological test battery (DST, VLT, SRT) | no | cognitive fatigue PSS GDS-SF BDNF WBV |
Korea [93] |
|
B. bifidum, B. longum 1 × 109 CFU 12 wk. |
healthy | 26 | 72.0 | 27 | 71.1 | CERAD-K | yes | BDNF | Korea [94] |
|
B. longum, B. infantis, B. breve, B. breve 1.25 × 1010 CFU 12 wk. |
healthy | 18 | 70.9 ± 3.2 | 20 | 69.9 ± 3.0 | MoCA-J Flanker task |
no | PHQ-9, GAD-7, MNA, energy intake, BMI, height, weight, blood pressure, bowel movement characteristics |
Japan [95] |
|
L. plantarum ≥ 1.25 × 1010 CFU/day fermented soybean 2 capsules, once a day 12 wk. |
MCI | 50 | 69.2 ± 7.0 | 50 | 68.0 ± 5.1 | CNT VLT ACPT DST |
yes | BDNF, height, weight, blood pressure and pulse rate, complete blood cell count and blood parameters | South Korea [98] |
|
B. breve > 1.0 × 1010 CFU/day 2 capsules 12 wk. |
MCI | 60 | 61.6 ± 6.4 | 61 | 61.5 ± 6.8 | MMSE RBANS |
no | hs-CRP haematological and biological blood parameters |
Japan [99] |
|
L. fermentum, L. plantarum, L. acidophilus, B. lactis, B. longum, B. bifidum 3 × 109 CFU/g of each 2 capsules, once a day 12 wk. |
AD | 23 | 80.6 ± 1.8 | 25 | 79.7 ± 1.7 | TYM | no | TAC, GSH, MDA, Il-6, Il-10, TNF-a, NO, 8-OHdG, weight, BMI | Iran [100] |
|
L. acidophilus, L. casei, L. fermentum B. bifidum, 2 × 109 CFU/g of each 200 mL probiotic milk/day 12 wk. |
AD | 30 | 82 ± 1.7 | 30 | 77.7 ± 2.6 | MMSE | no | TAC, GSH, hs-CRP, MDA, NO, HOMA-B, HOMA-IR, QUICK, FPG, TG, TC, LDL, HDL, VLDL, TC/HDL, insulin, weight, BMI dietary intakes (3-day food records) |
Iran [101] |
|
L. acidophilus, B. bifidum, B. longum 2 × 109 CFU/g each for probiotic capsule + selenium 200 ng/day 12 wk. |
AD | 52 | 78.8 ± 10.2 | 27 | 76.2 ± 8.1 | MMSE | no | TAC, GSH, hsCRP, insulin, HOMA-IR, QUICKI, TG, NO, FPG, MDA, TC, LDL, VLDL, HDL, TC/HDL, Gene expression related to inflammation, insulin and lipid metabolism BMI, weight, dietary intakes (3-day food records) |
Iran [102] |
| PREBIOTICS | |||||||||
|
Darmocare Pre® (inulin + fructooligosaccharides) 13 wk. |
non-demented | 22 | 73.4 ± 1.8 | 28 | 74.2 ± 1.6 | MMSE | no | Frailty Functional Impairment Sleep quality Blood analysis and haemogram |
Spain [103] |
| SYNBIOTIC | |||||||||
|
L. paracasei, L. ramnosus, L. acidophilus, B. lactis (108–109 CFU of each) + fructooligosaccharide twice a day 24 wk. |
apparently healthy | 24 | 77.0 ± 1.3 | 25 | 67.9 ± 4.5 | MMSE | no | GDS-15, % of body fat, IL-6, TNF-α, IL-10, DAO, IFABP, LPS | Brazil [104] |
Abbreviations: 8-OHdG, serum high sensitivity 8-hydroxy-2′-deoxyguanosine; ACPT, auditory continuous performance test; AD, Alzheimer’s Disease; BDNF, Brain-derived neurotrophic factor; CERAD-K, Consortium to Establish a Registry for Alzheimer’s Disease, The Korean version; CFU, colony-forming units; DAO, serum diamine-oxidase; DST, digit span test; DW2009, Lactobacillus plantarum C29-fermented soybean; FPG, fasting plasma glucose; GAD-7, Generalized Anxiety Disorder-7; GDS-SF, Geriatric Depression Scale, short form; GSH, total glutathione; HOMA-B, homeostatic model assessment for B-cell function; HOMA-IR, homeostasis model of assessment-insulin resistance; hs-CRP, high-sensitivity C-reactive protein; IFABP, intestinal fatty acid binding protein; IL-10, interleukin 10; LPS, lipopolysaccharide; MCI, Mild Cognitive Impairment; MDA, malondialdehyde; MMSE, Mini-Mental State Examination; MNA, Mini Nutritional Assessment; MoCA-J, Japanese version of the Montreal Cognitive Assessment instrument; NART, National Adult Reading Test; NO, nitric oxide; PHQ-9, Patient Health Questionnaire-9; POMS, The Short Form Of The Profile Of Mood States; PSS, perceived stress scale; QUICKI, quantitative insulin sensitivity check index; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; SRT, story recall test; TAC, total antioxidant capacity; TC, total cholesterol; TG, triglycerides; TNF-α, tumor necrosis factor α; VLT, verbal learning test; WBV, frictional force of blood flow in vessels.