Cited by 951Probiotics and Fermented FoodsDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index; none of the 44 sources its claims cite is checked for support yet.

Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial

Open access

Akbari, Elmira, Asemi, Zatollah, Daneshvar Kakhaki, Reza, Bahmani, Fereshteh, Kouchaki, Ebrahim, Tamtaji, Omid Reza, Hamidi, Gholam Ali, Salami, Mahmoud·2016·Frontiers in Aging Neuroscience

DOI 10.3389/fnagi.2016.00256PMC PMC5105117

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Abstract

Alzheimer's disease (AD) is associated with severe cognitive impairments as well as some metabolic defects. Scant studies in animal models indicate a link between probiotics and cognitive function. This randomized, double-blind and controlled clinical trial was conducted among 60 AD patients to assess the effects of probiotic supplementation on cognitive function and metabolic status. The patients were randomly divided into two groups (n=30 in each group) treating with either milk (control group) or a mixture of probiotic (probiotic group). The probiotic supplemented group took 200 ml/day probiotic milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum and Lactobacillus fermentum (2×109 CFU/g for each) for 12 weeks. Mini-mental state examination (MMSE) score was recorded in all subjects before and after the treatment. Pre- and post-treatment fasting blood samples were obtained to determine the related markers. After 12 weeks intervention, compared with the control group (-5.03%±3.00), the probiotic treated (+27.90%±8.07) patients showed a significant improvement in the MMSE score (P<0.001). In addition, changes in plasma malondialdehyde (-22.01%±4.84 vs. +2.67%±3.86 µmol/L, P<0.001), serum high-sensitivity C-reactive protein (-17.61%±3.70 vs. +45.26%±3.50 µg/mL, P<0.001), homeostasis model of assessment-estimated insulin resistance (+28.84%±13.34 vs.+76.95%±24.60, P=0.002), Beta cell function (+3.45%±10.91 vs. +75.62%±23.18, P=0.001), serum triglycerides (-20.29%±4.49 vs. -0.16%±5.24 mg/dL, P=0.003) and quantitative insulin sensitivity check index (-1.83±1.26 vs. -4.66±1.70, P=0.006) in the probiotic group were significantly varied compared to the control group. We found that the probiotic treatment had no considerable effect on other biomarkers of oxidative stress and inflammation, fasting plasma glucose and other lipid profiles. Overall, the current study demonstrated that probiotic consumption for 12 weeks positively affects cognitive function and some metabolic statuses in the AD patients.

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Written from the paper’s full text.

TL;DR

In a 12-week randomized, double-blind controlled trial of 60 Alzheimer’s disease patients, probiotic milk supplementation improved MMSE scores and some metabolic/inflammatory markers compared with control milk. The authors conclude probiotics may have favorable effects on cognition and selected metabolic statuses in AD, but not on all oxidative stress, inflammation, glucose, or lipid measures.

Key findings

MMSE score improved in the probiotic group (+27.90% ± 8.07) versus worsening in the control group (−5.03% ± 3.00; P < 0.001).
Probiotic treatment significantly changed plasma MDA (−22.01% ± 4.84 vs. +2.67% ± 3.86 μmol/L, P < 0.001), serum hs-CRP (−17.61% ± 3.70 vs. +45.26% ± 3.50 μg/mL, P < 0.001), HOMA-IR (+28.84% ± 13.34 vs. +76.95% ± 24.60, P = 0.002), HOMA-B (+3.45% ± 10.91 vs. +75.62% ± 23.18, P = 0.001), serum triglycerides (−20.29% ± 4.49 vs. −0.16% ± 5.24 mg/dL, P = 0.003), and QUICKI (−1.83 ± 1.26 vs. −4.66 ± 1.70, P = 0.006).
No considerable effect was found on other oxidative stress and inflammation biomarkers, fasting plasma glucose, or other lipid profiles (LDL, HDL, total cholesterol).
No side effects were reported following probiotic administration.

Methods

Randomized, double-blind, controlled 12-week clinical trial in 60 AD patients aged 60–95 years residing at welfare organizations in Kashan and Esfahan, Iran; participants were randomized to control milk (n = 30) or probiotic milk (n = 30), matched at baseline for disease severity based on gender, BMI, and age.
Probiotic group received 200 ml/day milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 10^9 CFU/g for each) for 12 weeks; control group received milk.
Primary outcome was MMSE; secondary outcomes included oxidative stress, inflammation, and metabolic biomarkers from fasting blood samples at weeks 0 and 12. Analyses used intention-to-treat with LOCF for missing values, independent t-tests, and ANCOVA adjustment for baseline biochemical values, age, and BMI.

Limitations

The paper states that measuring fecal bacteria loads before and after probiotic supplementation in AD patients was very difficult.
The paper states that cognition was assessed only with the MMSE, and that other cognitive criteria and additional inflammatory/oxidative biomarkers such as IL-6, TNF-α, catalase, and SOD would be informative.
Evident from the text: the sample was small (60 randomized; 52 completed), with deaths/dropouts during the study, and baseline serum triglycerides, VLDL, and HDL differed significantly between groups, although the authors report adjustment did not considerably change findings.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fnagi.2016.00256

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 44 cited sources checked · 0 supported · 0 flagged

A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Findings of the current study indicated that while the probiotic supplementation decreased the plasma MDA and the serum hs-CRP levels it was ineffective on other biomarkers of oxidative stress and inflammation.”
- Also stated in: § Discussion · boosted
  “Overall, the current study demonstrated that 12 weeks consumption of probiotic in the AD patients had favorable effects on MDA, hs-CRP, markers of insulin metabolism, and serum levels of triglyceride and VLDL.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Findings of the current study indicated that while the probiotic supplementation decreased the plasma MDA and the serum hs-CRP levels it was ineffective on other biomarkers of oxidative stress and inflammation.”
- Also stated in: § Discussion · plain
  “However, the pobiotic treatment was inefective on other biomarkers of oxidative stress and inflammation, FPG, and other lipid profiles.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

Show all 27 claims

It may state two separate claims as one. 23
Probably not a substantial claim. 35

In the paper
“The MMSE was used to assess cognition in the AD subjects (Folstein et al., 1975).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Materials and methods > Assessment of outcomes
What the sources say
- Not checked yetcites Folstein et al., 1975 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.
In the paper
“In our previous work, we have shown that probiotics efficiently reverse the impaired spatial learning and memory as well as synaptic transmission in diabetes mellitus (Davari et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Davari et al., 2013 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is demonstrated that other brain related disorders such as multiple sclerosis (Kouchaki et al., 2016) and stress are also influenced by probiotics (Liang et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Kouchaki et al., 2016 source
- Not checked yetcites Liang et al., 2015 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased biomarkers of oxidative stress (Furman et al., 2016), inflammation and chronic neuroinflammation are reported to be associated with many neurodegenerative disorders of central nervous system (CNS) including AD (Leszek et al., 2016).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Background
What the sources say
- Not checked yetcites Furman et al., 2016 source
- Not checked yetcites Leszek et al., 2016 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Gareau reported that intestinal dysbiosis in germ free animals (containing no microbiota), bacterial infection with an enteric pathogen and administration of probiotics can modulate cognitive behaviors including learning and memory (Gareau, 2014).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Background
What the sources say
- Not checked yetcites Gareau, 2014 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AD patients are predisposed to some complications including increased oxidative stress (Sultana et al., 2011), morbidity, mortality (Schelke et al., 2016), microvascular disease, dyslipidemia, and insulin resistance (Sridhar et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Sultana et al., 2011 source
- Not checked yetcites Schelke et al., 2016 source
- Not checked yetcites Sridhar et al., 2015 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Missing values were treated based on Last-Observation-Carried-Forward method (LOCF) (Lachin, 2016).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Materials and methods > Statistical methods
What the sources say
- Not checked yetcites Lachin, 2016 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Probiotics intake may improve markers of insulin metabolism and lipid profiles by reducing cytokines and suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (Shi et al., 2006) and gut microbiota-short chain fatty acids (SCFA)-hormone axis (Yadav et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Shi et al., 2006 source
- Not checked yetcites Yadav et al., 2013 source
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Consumption of symbiotic bread containing the heat-resistant probiotic Lactobacillus sporogenes (1 × 108 CFU/g) for 8 weeks also decreased the serum triglyceride and VLDL concentrations in patients with type 2 diabetes (Shakeri et al., 2014).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Shakeri et al., 2014 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Accordingly, high lipid levels could be one of the risk factors for AD (Reitz et al., 2010).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Reitz et al., 2010 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Oxidative stress is a frequently observed feature of AD, although its pathological significance is not understood (Selvarajah et al., 2011).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Selvarajah et al., 2011 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Evidence indicates that, through production of reactive oxygen species, oxidative stress acts as vehicle for deposition and accumulation of amyloid β (Aβ) in AD (Kim et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Kim et al., 2015 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For example, it was reported that 6 weeks probiotic treatment caused no significant change in inflammatory factors of diabetic patients (Mazloom et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Mazloom et al., 2013
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Dysfunctions in GABA-signaling are linked to anxiety and depression, defects in synaptogenesis and cognitive impairments (Aziz et al., 2013; Mitew et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Aziz et al., 2013 source
- Not checked yetcites Mitew et al., 2013 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Also the glutamatergic NMDA receptors are involved in the most important excitatory neurotransmission of brain (Talaei et al., 2016) which is engaged in the neural circuits involved in learning and memory.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Talaei et al., 2016 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Furthermore, 8 weeks consumption of capsules containing 108 CFU/g of L. casei by the people suffered from rheumatoid arthritis displayed no significant within- and between-group changes in MDA and TAC levels (Vaghef-Mehrabany et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Vaghef-Mehrabany et al., 2015 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In addition, Zarrati et al. (2014) showed that 8 weeks consumption of yogurt, enriched by L. acidophilus, Bifidobacterium langum, and L. casei (108 CFU/g each) decreased inflammatory cytokines in overweight people.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Zarrati et al., 2014 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Some evidence from clinical studies support the fact that abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction (Wang et al., 2014).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Wang et al., 2014 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Further, findings from germ free animals indicated a decreased level of brain derived neurotrophic factor (BDNF), important neurotrophic factor in the neuronal growth and survival, and a reduced expression of some subunits of N-Methyl-D-aspartate (NMDA) receptors (Sudo et al., 2004) involved in most abundant neurotransmission in brain (Salami et al., 2000).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Sudo et al., 2004 source
- Not checked yetcites Salami et al., 2000 source
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Emerging evidence has demonstrated that brain insulin resistance, as a key mediator in prediabetes and diabetes mellitus, may take a role in AD (Cervellati et al., 2016).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Cervellati et al., 2016 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It has also been postulated that oxidative stress may decrease the activity of α-secretase, which promotes the expression and activity of β and γ-secretase, leading to the increased production of Aβ (Tan et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Tan et al., 2013 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients (Ma et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Ma et al., 2015
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Consistently, in a meta-analysis study, Kasińska and Drzewoski (2015) reported a reduced HOMA-IR and insignificant FGP in probiotic treated subjects.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Kasińska and Drzewoski, 2015
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Consistent to our findings, a significant reduction in MDA levels was reported in type 2 diabetic patients after consuming probiotic yogurt (Ejtahed et al., 2012).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Ejtahed et al., 2012 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.

50 of 50

The paper relies on this without support.
No direct study has considered gut microbiota manipulation in Alzheimer's disease patients.
“However, no direct study has considered the gut microbiota manipulation in AD patients.”
The paper relies on this without support.
Studies considering the effect of probiotic supplements on brain behavioral phenomena are scant.
“Studies considering the effect of probiotic supplements on brain behavioral phenomena are scant.”
The paper relies on this without support.
This study is the first to evaluate the beneficial effects of probiotic supplementation on cognitive function, biomarkers of oxidative stress, inflammation, and metabolic status in patients with Alzheimer's disease.
“To the best of our knowledge, this study is the first evaluating the beneficial effects of probiotic supplementation on cognitive function, biomarkers of oxidative stress, inflammation and metabolic status in patients with AD.”
The paper relies on this without support.
The probiotic intervention changed the gut microbiota in the AD patients.
“Measurement of fecal bacteria loads before and after the probiotic supplementation in the AD patients was very difficult.”

4 of 4

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2 retracted

RETRACTED: Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial
Kouchaki, E., Tamtaji, O. R., Salami, M., Bahmani, F., Daneshvar Kakhaki, R., Akbari, E., Tajabadi-Ebrahimi, M., Jafari, P., & Asemi, Z. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2016.08.015 · Cited by 317 · cited 1×
“It is demonstrated that other brain related disorders such as multiple sclerosis (Kouchaki et al., 2016) and stress are also influenced by probiotics (Liang et al., 2015).”
BackgroundSelf-citation
Retracted
RETRACTED ARTICLE: The effects of probiotics on mental health and hypothalamic–pituitary–adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers
Mohammadi, A. A., Jazayeri, S., Khosravi‐Darani, K., Solati, Z., Mohammadpour, N., Asemi, Z., Adab, Z., Djalali, M., Tehrani‐Doost, M., Hosseini, M., et al. (2015) · Nutritional Neuroscience · doi:10.1179/1476830515y.0000000023 · Cited by 241
Self-citation
Retracted
“Mini-mental state”
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · cited 2×
“It is generally agreed that probiotic strains should be of host origin with a beneficial effect on the host, withstand into food stuff with a high count, withstand transits through intestine and colonize lumen of the tract, produce antimicrobial agents, and technologically appropriate for…”
BackgroundMethod
Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
The Ferric Reducing Ability of Plasma (FRAP) as a Measure of “Antioxidant Power”: The FRAP Assay
Benzie, I. F. F., & Strain, J. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0292 · Cited by 23,027 · cited 1×
“Plasma total antioxidant capacity (TAC) was measured using the ferric reducing antioxidant power method developed by Benzie and Strain (1996).”
Method
[Japanese version of the Neuropsychiatric Inventory--a scoring system for neuropsychiatric disturbance in dementia patients].
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,012
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Older Adults' Reasons for Using Technology while Aging in Place
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Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
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Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572 · cited 2×
“The difference between the two groups of testing was statistically significant (P < 0.001).”
BackgroundInfluential

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Shewale, 2014, Selection criteria for probiotics: a review, Int. J. Probiotics Prebiotics, 9, 17

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Verma, H., Phian, S., Lakra, P., Kaur, J., Subudhi, S., Lal, R., & Rawat, C. D. (2020) · Indian Journal of Microbiology · doi:10.1007/s12088-020-00898-z · Cited by 35
Dietary Interventions to Prevent or Delay Alzheimer’s Disease: What the Evidence Shows
Bartochowski, Z., Conway, J., Wallach, Y., Chakkamparambil, B., Alakkassery, S., & Grossberg, G. T. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00333-1 · Cited by 31
Personalizing the Care and Treatment of Alzheimer’s Disease: An Overview
Štrac, D. Š., Konjevod, M., Šagud, M., Perković, M. N., Erjavec, G. N., Vuić, B., Šimić, G., Vukić, V., Mimica, N., & Pivac, N. (2021) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s284615 · Cited by 30
“On the other hand, the use of probiotics and prebiotics seems to reduce the risk of AD(123) and improve cognition in AD patients.(124) It was already shown that the diet might influence the development of AD.”
Background
Probiotics as potential therapeutic options for Alzheimer’s disease
Ji, H., & Shen, L. (2021) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-021-11607-1 · Cited by 32
Chronic Rhinosinusitis and Alzheimer’s Disease—A Possible Role for the Nasal Microbiome in Causing Neurodegeneration in the Elderly
Harrass, S., Yi, C., & Chen, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011207 · Cited by 31
Hawthorn flavonoid ameliorates cognitive deficit in mice with Alzheimer's disease by increasing the levels of Bifidobacteriales in gut microbiota and docosapentaenoic acid in serum metabolites
Zhang, J., Hao, J., Liu, R., Wu, T., Liu, R., Sui, W., & Zhang, M. (2022) · Food & Function · doi:10.1039/d2fo02871a · Cited by 30
A Randomized Controlled Trial of Probiotics Targeting Gut Dysbiosis in Huntington’s Disease
Wasser, C. I., Mercieca, E., Kong, G., Hannan, A. J., Allford, B., McKeown, S. J., Stout, J. C., & Glikmann‐Johnston, Y. (2023) · Journal of Huntington s Disease · doi:10.3233/jhd-220556 · Cited by 30
Psychobiotics for Mitigation of Neuro‐Degenerative Diseases: Recent Advancements
Dhyani, P., Goyal, C., Dhull, S. B., Chauhan, A. K., Saharan, B. S., Harshita, Duhan, J. S., & Gökşen, G. (2023) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202300461 · Cited by 30
Commentary: Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial
Leblhuber, F., Egger, M., Schuetz, B., & Fuchs, D. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00054 · Cited by 30
“These investigations should include the bacterial taxa as well as the serum and intestinal inflammation markers mentioned above together with the metabolic parameters mentioned by Akbari et al. (2016).”
Background
The gut-immune-brain axis in neurodevelopment and neurological disorders
Park, J. C., & Im, S. (2022) · Microbiome Research Reports · doi:10.20517/mrr.2022.11 · Cited by 34
Exploring the Mechanistic Interplay between Gut Microbiota and Precocious Puberty: A Narrative Review
Yue, M., & Zhang, L. (2024) · Microorganisms · doi:10.3390/microorganisms12020323 · Cited by 31
Mechanism of microglia-mediated neuroinflammation, associated cognitive dysfunction, and therapeutic updates in Alzheimer's disease
Ghimire, A., Rehman, S. A., Subhani, A., Khan, M. A., Rahman, Z., Iqubal, M. K., & Iqubal, A. (2025) · hLife · doi:10.1016/j.hlife.2024.11.006 · Cited by 32
“Notably, in a randomized clinical trial, the use of probiotics for 3 months showed reduced oxidative stress and reduced levels of C-reactive protein (CRP) and malo-naldehyde (MDA) (QUICKI trial) [102].”
Specific changes in faecal microbiota are associated with familial Mediterranean fever
Deshayes, S., Fellahi, S., Bastard, J., Launay, J., Callebert, J., Fraisse, T., Buob, D., Boffa, J., Giurgea, I., Dupont, C., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-215258 · Cited by 29
Transcranial Ultrasound Stimulation of Hypothalamus in Aging Mice
Pang, N., Huang, X., Zhou, H., Xia, X., Liu, X., Wang, Y., Meng, W., Bian, T., Meng, L., Xu, L., et al. (2020) · IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control · doi:10.1109/tuffc.2020.2968479 · Cited by 30
Associations between the Intake of Different Types of Dairy and Cognitive Performance in Dutch Older Adults: The B-PROOF Study
de Goeij, L. C., van de Rest, O., Feskens, E. J. M., de Groot, C. P. G. M., & Brouwer-Brolsma, E. M. (2020) · Nutrients · doi:10.3390/nu12020468 · Cited by 31
The effect of alpha lipoic acid on passive avoidance and social interaction memory, pain perception, and locomotor activity in REM sleep-deprived rats
Mahdavi, M. S., Nasehi, M., Vaseghi, S., Mousavi, Z., & Zarrindast, M. (2020) · Pharmacological Reports · doi:10.1007/s43440-020-00161-8 · Cited by 29
Association Between Consumption of Fermented Food and Food-Derived Prebiotics With Cognitive Performance, Depressive, and Anxiety Symptoms in Psychiatrically Healthy Medical Students Under Psychological Stress: A Prospective Cohort Study
Karbownik, M. S., Mokros, Ł., Dobielska, M., Kowalczyk, M., & Kowalczyk, E. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.850249 · Cited by 33
The Intestine as a Lifespan- and Proteostasis-Promoting Signaling Tissue
Hodge, F., Bajuszova, V., & van Oosten‐Hawle, P. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.897741 · Cited by 29
Latent Potential of Multifunctional Selenium Nanoparticles in Neurological Diseases and Altered Gut Microbiota
Ashraf, H., Cossu, D., Ruberto, S., Noli, M., Jasemi, S., Simula, E. R., & Sechi, L. A. (2023) · Materials · doi:10.3390/ma16020699 · Cited by 33
Probiotics- its functions and influence on the ageing process: A comprehensive review
Choudhary, P., Kathuria, D., Suri, S., Bahndral, A., & Naveen, A. K. (2023) · Food Bioscience · doi:10.1016/j.fbio.2023.102389 · Cited by 36
Bridging the gap: associations between gut microbiota and psychiatric disorders
Ahmed, G. K., Ramadan, H. K., Elbeh, K., & Haridy, N. A. (2024) · Middle East Current Psychiatry · doi:10.1186/s43045-024-00395-9 · Cited by 33
Radiation-Induced Brain Injury: Mechanistic Insights and the Promise of Gut–Brain Axis Therapies
Li, M., Tong, F., Wu, B., & Dong, X. (2024) · Brain Sciences · doi:10.3390/brainsci14121295 · Cited by 31
Microbial Therapeutics in Neurocognitive and Psychiatric Disorders
Alagiakrishnan, K., & Halverson, T. (2021) · Journal of Clinical Medicine Research · doi:10.14740/jocmr4575 · Cited by 29
“Two RCTs showed that probiotic supplementation led to a significant improvement in cognitive function in AD with modulation of brain activity [83, 160].”
BackgroundInfluential
Etiology and management of Alzheimer’s disease: Potential role of gut microbiota modulation with probiotics supplementation
Dasriya, V. L., Samtiya, M., Dhewa, T., Puniya, M., Kumar, S., Ranveer, S. A., Chaudhary, V., Vij, S., Behare, P. V., Singh, N., et al. (2021) · Journal of Food Biochemistry · doi:10.1111/jfbc.14043 · Cited by 29
Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia
Meng, H. Y. H., Mak, C. C. H., Mak, J. W. Y., Zuo, T., Ko, H., & Chan, F. K. L. (2022) · European Journal of Nutrition · doi:10.1007/s00394-021-02760-4 · Cited by 31
Intestinal Microbiota Remodeling Protects Mice from Western Diet-Induced Brain Inflammation and Cognitive Decline
Jena, P. K., Setayesh, T., Sheng, L., Lucente, J. D., Jin, L. W., & Wan, Y. Y. (2022) · Cells · doi:10.3390/cells11030504 · Cited by 26
Alzheimer’s Disease Treatment: The Search for a Breakthrough
Reiss, A. B., Muhieddine, D., Jacob, B., Mesbah, M., Pinkhasov, A., Gomolin, I. H., Stecker, M. M., Wısnıewskı, T., & Leon, J. D. (2023) · Medicina · doi:10.3390/medicina59061084 · Cited by 31
Interplay between microglia and environmental risk factors in Alzheimer's disease
Zhang, M., Liang, C., Chen, X., Cai, Y., & Cui, L. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.389745 · Cited by 30
Microbial diversity and fitness in the gut–brain axis: influences on developmental risk for Alzheimer’s disease
Jamerlan, A., An, S. S. A., & Hulme, J. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2486518 · Cited by 34
“135,136 Recent clinical studies on probiotic supplementation to alleviate the impact of AD showed promising results, consistent with the findings from animal models.”
Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease
Fülöp, T., Tripathi, S., Rodrigues, S., Desroches, M., Bunt, T., Eiser, A. R., Bernier, F., Beauregard, P. B., Barron, A. E., Khalil, A., et al. (2021) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s264910 · Cited by 27
Protective Effects of Bacillus coagulans JA845 against D-Galactose/AlCl3-Induced Cognitive Decline, Oxidative Stress and Neuroinflammation
Song, X., Zhao, Z., Zhao, Y., Jin, Q., & Li, S. (2021) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2111.11031 · Cited by 27
“Interestingly, growing evidences suggested that probiotics have beneficial effects on the delay of AD progression [16].”
Background
Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Mild Cognitive Impairment and Alzheimer's Disease: A Meta-Analysis
Li, X., Lv, C., Jin-xiao, S., & Li, J. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.757673 · Cited by 28
Relationship Between the Gut Microbiota and Alzheimer’s Disease: A Systematic Review
Cordero, E. M. G., Cuevas‐Budhart, M. Á., Pérez-Morán, D., Villeda, M. Á. T., & García-Madrid, M. G. D. P. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215224 · Cited by 28
Gut brain regulation using psychobiotics for improved neuropsychological illness
Deepika, Shukla, A. K., Kumari, A., & Kumar, A. (2023) · Developmental Psychobiology · doi:10.1002/dev.22404 · Cited by 28
Cross-species examination of single- and multi-strain probiotic treatment effects on neuropsychiatric outcomes
Joseph, J., & Law, C. A. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.11.010 · Cited by 26
A systematic review and meta-analysis: The effects of probiotic supplementation on metabolic profile in patients with neurological disorders
Tamtaji, O. R., Milajerdi, A., Reiner, Ž., Asemi, Z., Dadgostar, E., Heidari‐Soureshjani, R., Mamsharifi, P., Amirani, E., Mirzaei, H., Hallajzadeh, J., et al. (2020) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2020.102507 · Cited by 27
Self-citation
A review of potential microbiome-gut-brain axis mediated neurocognitive conditions in persons living with HIV
Rich, S. N., Klann, E. M., Bryant, V. E., Richards, V. L., Wijayabahu, A. T., BRYANT, K. J., Mai, V., & Cook, R. L. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100168 · Cited by 27
The Effects of Probiotic Supplementation on Opioid‐Related Disorder in Patients under Methadone Maintenance Treatment Programs
Molavi, N., Rasouli‐Azad, M., Mirzaei, H., Matini, A. H., Banafshe, H. R., Valiollahzadeh, M., Hassanzadeh, M., Saghazade, A. R., Abbaszadeh‐Mashkani, S., Mamsharifi, P., et al. (2022) · International Journal of Clinical Practice · doi:10.1155/2022/1206914 · Cited by 26
The Therapeutic Role of Exercise and Probiotics in Stressful Brain Conditions
Martínez‐Guardado, I., Arboleya, S., Pérez, F. J. G., Kaliszewska, A., Gueimonde, M., & Arias, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073610 · Cited by 27
Manipulation of the diet–microbiota–brain axis in Alzheimer’s disease
Lee, D. D., Lee, V. M. ‐., & Hur, S. K. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1042865 · Cited by 27
“The Mediterranean-style diet (MeDi) lowers the risk of deficiencies in micronutrient intake and balances the intake of certain macronutrients, as it supplies high amounts of B group vitamins, antioxidant vitamins (vitamins E and C), and carotenes while increasing monounsaturated fatty acid (MUFA) consumption (Castro-Q…”
Background
New Insights into the Gut Microbiota in Neurodegenerative Diseases from the Perspective of Redox Homeostasis
Wang, Y., Zhang, Z., Li, B., He, B., Li, L., Nice, E. C., Zhang, W., & Xu, J. F. (2022) · Antioxidants · doi:10.3390/antiox11112287 · Cited by 30
Role of microbial dysbiosis in the pathogenesis of Alzheimer's disease
Susmitha, G., & Kumar, R. K. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109478 · Cited by 27
Using Zebrafish to Investigate Interactions Between Xenobiotics and Microbiota
Catron, T. R., Gaballah, S., & Tal, T. L. (2019) · Current Pharmacology Reports · doi:10.1007/s40495-019-00203-7 · Cited by 26
Effects of probiotics fermented milk products on obesity measure among adults: A systematic review and meta-analysis of clinical trials
Mohammadi, H., Ghavami, A., Faghihimani, Z., Sharifi, S., Nattagh‐Eshtivani, E., Ziaei, R., & Miraghajani, M. S. (2021) · Journal of Functional Foods · doi:10.1016/j.jff.2021.104494 · Cited by 29
Microbiota–gut–brain axis: the mediator of exercise and brain health
Kang, P., & Wang, A. (2024) · Psychoradiology · doi:10.1093/psyrad/kkae007 · Cited by 31
“…Lactobaccilus acidophilus , Lactobacillus casei , Bifidobacterium bifidum , and Lactobacillus fermen-tum would have favorable effects on reducing plasma malondialdehyde and serum high-sensiti vity C-reacti ve protein levels, indicating a decrease in inflammatory responses (Akbari et al. , 2016 ).”
Background
The Relationship between Gut Microbiome and Cognition in Older Australians
Komanduri, M., Savage, K. M., Lea, A., McPhee, G. M., Nolidin, K., Deleuil, S., Stough, C. K. K., & Gondalia, S. V. (2021) · Nutrients · doi:10.3390/nu14010064 · Cited by 26
The Use of Probiotic Therapy in Metabolic and Neurological Diseases
Lee, S. H. F., Ahmad, S. R., Lim, Y. C., & Zulkipli, I. N. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.887019 · Cited by 26
A New Concept of Associations between Gut Microbiota, Immunity and Central Nervous System for the Innovative Treatment of Neurodegenerative Disorders
Yoshikawa, S., Taniguchi, K., Sawamura, H., Ikeda, Y., Tsuji, A., & Matsuda, S. (2022) · Metabolites · doi:10.3390/metabo12111052 · Cited by 25
Immunomodulatory effects of probiotic supplementation in patients with asthma: a randomized, double-blind, placebo-controlled trial
Sadrifar, S., Abbasi-Dokht, T., Forouzandeh, S., Malek, F., Yousefi, B., Farrokhi, A. S., Karami, J., & Baharlou, R. (2023) · Allergy Asthma and Clinical Immunology · doi:10.1186/s13223-022-00753-4 · Cited by 27
Soybean polyenylphosphatidylcholine (PPC) is beneficial in liver and extrahepatic tissue injury: An update in experimental research
Mak, K. M., & Shekhar, A. C. (2023) · The Anatomical Record · doi:10.1002/ar.25333 · Cited by 25
“These bacteria also have beneficial effects for diseases, such as irritable bowel syndrome (Williams, 2010) and Alzheimer disease (Akbari et al., 2016).”
Background
Imaging of brain glucose uptake by PET in obesity and cognitive dysfunction: life-course perspective
Iozzo, P., & Guzzardi, M. A. (2019) · Endocrine Connections · doi:10.1530/ec-19-0348 · Cited by 25
The Link Between Nutrition and Alzheimer’s Disease: From Prevention to Treatment
Martins, L. B., Silveira, A. L. M., & Teixeira, A. L. (2021) · Neurodegenerative Disease Management · doi:10.2217/nmt-2020-0023 · Cited by 26
Treatment with Bifidobacteria can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice
Wu, Q., Li, Q., Zhang, X., Ntim, M., Wu, X., Li, M., Wang, L., Zhao, J., & Li, S. (2020) · PeerJ · doi:10.7717/peerj.10262 · Cited by 25
“These results conform to our hypothesis (Akbari et al., 2016).”
Effect of probiotics on cognitive function in adults with mild cognitive impairment or Alzheimer's disease: A meta-analysis of randomized controlled trials
Mo, R., Jiang, M., Xu, H., & Jia, R. (2024) · Medicina Clínica · doi:10.1016/j.medcli.2024.01.013 · Cited by 23
Gut Microbiota as a Hidden Player in the Pathogenesis of Alzheimer’s Disease
Choi, H., Lee, D., & Mook‐Jung, I. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215235 · Cited by 24
Effect of fermented foods on some neurological diseases, microbiota, behaviors: mini review
Eroğlu, F. E., & Şanlıer, N. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2053060 · Cited by 25
Application of Functional and Edible Coatings and Films as Promising Strategies for Developing Dairy Functional Products—A Review on Yoghurt Case
Salama, H. H., Trif, M., Alexandru Vasile, R. U. S. U., & Bhattacharya, S. (2022) · Coatings · doi:10.3390/coatings12060838 · Cited by 24
The emerging role of the microbiome in Alzheimer's disease
Wasén, C., Simonsen, E., Ekwudo, M. N., Profant, M. R., & Cox, L. M. (2022) · International review of neurobiology · doi:10.1016/bs.irn.2022.09.001 · Cited by 24
Lactobacillaceae improve cognitive dysfunction via regulating gut microbiota and suppressing Aβ deposits and neuroinflammation in APP/PS1 mice
Wu, Y., Niu, X., Li, P., Tong, T., Wang, Q., Zhang, M., Li, Y., Liu, J., & Li, Z. (2023) · Archives of Microbiology · doi:10.1007/s00203-023-03466-3 · Cited by 27
Bifidobacterium breve Probiotic Compared to Lactobacillus casei Causes a Better Reduction in Demyelination and Oxidative Stress in Cuprizone-Induced Demyelination Model of Rat
Hasaniani, N., Ghasemi‐Kasman, M., Halaji, M., & Rostami-Mansoor, S. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03593-4 · Cited by 23
“A previous study indicated that these genes play a critical role in modulating astrocyte function and remyelination rate [32].”
Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders
Villavicencio-Tejo, F., Olesen, M. A., Navarro, L., Calisto, N., Iribarren, C., GARCÍA, K. P., Corsini, G., & Quintanilla, R. A. (2023) · Neurotoxicity Research · doi:10.1007/s12640-023-00681-0 · Cited by 24
“Nevertheless, preclinical studies have indicated that the intake of probiotics and even fecal transplantation (FTM) of healthy patients can improve intestinal function and consequently mitigate symptoms in dementias (Akbari et al. 2016; Tamtaji et al. 2019; Mazzini et al. 2018; Xu et al. 2021).”
Utility of Probiotics for Maintenance or Improvement of Health Status in Older People — A Scoping Review
Setbo, E., Campbell, K. L., Cuív, P. Ó., & Hubbard, R. E. (2019) · The journal of nutrition health & aging · doi:10.1007/s12603-019-1187-9 · Cited by 23
“The average score in the treatment group was 10.57 at the end of three months where the controls had declined on average to a score of 8.00 (p=0.01) (48).”
Influential
Whole brain radiotherapy induces cognitive dysfunction in mice: key role of gut microbiota
Luo, X.-X., Yang, C., Zhan, G.-F., Li, S., Hua, D.-Y., Luo, A.-L., & Yuan, X.-L. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05520-0 · Cited by 23
Exploring the potential of probiotics in Alzheimer's disease and gut dysbiosis
Sowmiya, S., Ls, D., Rajendran, P., Harikrishnan, N., & Ankul Singh, S. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.11.004 · Cited by 22
Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease
Hajjeh, O., Rajab, I. M., Bdair, M., Saife, S., Zahran, A., Nazzal, I., AbuZahra, M. I., Jallad, H., Abukhalil, M. M., Hallak, M., et al. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.03.015 · Cited by 23
Current Research in Fermented Foods: Bridging Tradition and Science
Sampsell, K., Marcolla, C. S., Tapping, S., Fan, Y., Sánchez-Lafuente, C. L., Willing, B. P., Reimer, R. A., & Burton, J. P. (2025) · Advances in Nutrition · doi:10.1016/j.advnut.2025.100554 · Cited by 28
“…participants with Alzheimer ’ s disease found that daily consumption of 200 mL milk fermented with L. acidophilus , Lacticaseibacillus casei , B. bifidum , and Limosilactobacillus fermentum (2 × 10 9 CFU/g each) for 12 wk improved mini-mental state examination scores compared with controls [104].”
Impact of Gut Microbiota on Radiation-Associated Cognitive Dysfunction and Neuroinflammation in Mice
Luo, N., Zhu, W., Li, X., Fu, M., Peng, X., Yang, F., Zhang, Y., Yin, H., Yang, C., Zhao, J., et al. (2021) · Radiation Research · doi:10.1667/rade-21-00006.1 · Cited by 21
Mechanical Bowel Preparation Is a Risk Factor for Postoperative Delirium as It Alters the Gut Microbiota Composition: A Prospective Randomized Single-Center Study
Yang, Z., Tong, C., Qian, X., Wang, H., & Wang, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.847610 · Cited by 22
Different oral and gut microbial profiles in those with Alzheimer's disease consuming anti-inflammatory diets
Chen, L., Wang, B., Liu, J., Wu, X., Xu, X., Cao, H., Ji, X., Zhang, P., Li, X., Hou, Z., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.974694 · Cited by 22
The effects of microbiome-targeted therapy on cognitive impairment and postoperative cognitive dysfunction—A systematic review
Sugita, S., Tahir, P., & Kinjo, S. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281049 · Cited by 24
Dietary interventions and cognition of Alzheimer’s disease patients: a systematic review of randomized controlled trial
Moreira, S. C., Jansen, A. K., & Silva, F. M. (2020) · Dementia & Neuropsychologia · doi:10.1590/1980-57642020dn14-030008 · Cited by 23
Potential therapeutic effects of boswellic acids/Boswellia serrata extract in the prevention and therapy of type 2 diabetes and Alzheimer’s disease
Gomaa, A. A., Farghaly, H. A., Abdel-Wadood, Y. A., & Gomaa, G. A. (2021) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-021-02154-7 · Cited by 24
Dairy Product Consumption and Changes in Cognitive Performance: Two‐Year Analysis of the PREDIMED‐Plus Cohort
Ni, J., Nishi, S. K., Babió, N., Martínez‐González, M. Á., Corella, D., Castañer, O., Martínez, J. A., Alonso‐Gómez, Á. M., Gómez‐Gracia, E., Vioqué, J., et al. (2022) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202101058 · Cited by 22
Bacteria-driven bio-therapy: From fundamental studies to clinical trials
Yu, Y., Lin, S., Chen, Z., Qin, B. Y., He, Z., Cheng, M., Sun, M., & Sun, J. Y. (2022) · Nano Today · doi:10.1016/j.nantod.2022.101731 · Cited by 23
Impact of probiotics on cognition and constipation in the elderly: A meta-analysis
Recharla, N., Choi, J., Puligundla, P., Park, S., & Lee, H. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e18306 · Cited by 21
Bifidobacterium animalis subsp. lactis A6 attenuates hippocampal damage and memory impairments in an ADHD rat model
Yin, X., Liu, W., Feng, H., Huang, J., Wang, Q., Zhang, Q., He, J., & Wang, R. (2024) · Food & Function · doi:10.1039/d3fo04665f · Cited by 23
Effects of probiotic therapy on serum inflammatory markers: A systematic review and meta-analysis
Maia, L. P., Levi, Y. L. D. A. S., do Prado, R. L., Santinoni, C. D. S., & Marsicano, J. A. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.01.051 · Cited by 21
Role of microbes in the pathogenesis of neuropsychiatric disorders
Goswami, A., Wendt, F. R., Pathak, G. A., Tylee, D. S., Angelis, F. D., Lillo, A. D., & Polimanti, R. A. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100917 · Cited by 21
Small intestinal bacterial overgrowth in Alzheimer’s disease
Kowalski, K., & Mulak, A. (2021) · Journal of Neural Transmission · doi:10.1007/s00702-021-02440-x · Cited by 19
“Interestingly, probiotic supplementation in AD patients have been demonstrated to improve cognitive function assessed by the MMSE (Akbari et al. 2016; Tamtaji et al. 2019).”
MethodInfluential
Probiotics as Potential Treatments for Neurodegenerative Diseases: a Review of the Evidence from in vivo to Clinical Trial
Kim, J. H., Choi, Y., Lee, S.-M., & Oh, M. S. (2024) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2024.215 · Cited by 22
Role of the gut microbiome in Alzheimer’s disease
Chok, K. C., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0122 · Cited by 22
Effects of probiotic supplementation on cognitive function in elderly: A systematic review and Meta-analysis
Tahmasbi, F., Mirghafourvand‬‬‬‬‬‬‬‬‬‬‬‬‬‬, M., Shamekh, A., Mahmoodpoor, A., & Sanaie, S. (2021) · Aging & Mental Health · doi:10.1080/13607863.2021.1966743 · Cited by 20
The Role of the Gut Microbiota and Microbial Metabolites in the Pathogenesis of Alzheimer’s Disease
Wang, Y. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220417005115 · Cited by 21
Non-Pharmacological Therapeutic Options for the Treatment of Alzheimer’s Disease
Huynh, Q., Elangovan, S., & Holsinger, R. M. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911037 · Cited by 20
Nutrition in Alzheimer’s disease: a review of an underappreciated pathophysiological mechanism
Jiang, J., Shi, H., Jiang, S., Wang, A., Zou, X., Wang, Y., Li, W., Zhang, Y., Sun, M., Ren, Q., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-022-2276-6 · Cited by 20
“A randomized, double-blind, controlled trial indicated that administering 200 mL of milk containing Lactobacillus acidophilus , L . casei , Bifidobacterium bifidum , and L . fermentum daily for 12 weeks could promote cognitive function and metabolic status in patients with AD (Akbari et al., 2016).”
Background
Influence of gut microbiota on the development of most prevalent neurodegenerative dementias and the potential effect of probiotics in elderly: A scoping review
Mateo, D., Marquès, M., Domingo, J. L., & Torrente, M. (2023) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32959 · Cited by 20
Incorporation of Probiotics and Other Functional Ingredients in Dairy Fat-Rich Products: Benefits, Challenges, and Opportunities
Gaba, K., & Anand, S. K. (2023) · Dairy · doi:10.3390/dairy4040044 · Cited by 20
“Previous studies have shown that probiotics were successful in preventing some diseases, including necrotizing enterocolitis, lactose intolerance, ulcerative colitis, infections of Salmonella , rheumatoid arthritis, obesity, Alzheimer’s disease, and infantile colic [64–70].”
Gut Microbiome in Alzheimer’s Disease: from Mice to Humans
Liang, C., Pereira, R., Zhang, Y., & Rojas, O. L. (2024) · Current Neuropharmacology · doi:10.2174/1570159x22666240308090741 · Cited by 27
“Akbari et al [117] conducted a clinical trial to assess the pro-biotics in AD patients.”
Background
Metabolic Status Influences Probiotic Efficacy for Depression—PRO-DEMET Randomized Clinical Trial Results
Gawlik-Kotelnicka, O., Margulska, A., Płeska, K., Skowrońska, A., & Strzelecki, D. (2024) · Nutrients · doi:10.3390/nu16091389 · Cited by 24
“Psychobiotics may have a wide range of uses, from improved mood and reduced stress levels to acting as an adjuvant in the therapeutic treatment of several neurodevelopmental and neurodegenerative illnesses [17–21].”
Background
Current Perspectives and Mechanisms of Relationship between Intestinal Microbiota Dysfunction and Dementia: A Review
Welcome, M. O. (2018) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000492491 · Cited by 22
The Microbiota–Human Health Axis
John, H. T., Thomas, T. C., Chukwuebuka, E. C., Ali, A. B., Anass, R., Tefera, Y. Y., Babu, B., Negruţ, N., Ferician, A. C., & Marian, P. (2025) · Microorganisms · doi:10.3390/microorganisms13040948 · Cited by 27
Microecologics and Exercise: Targeting the Microbiota–Gut–Brain Axis for Central Nervous System Disease Intervention
Peng, Z., Hou, T., Yang, K., Zhang, J., Mao, Y.-H., & Hou, X. (2025) · Nutrients · doi:10.3390/nu17111769 · Cited by 21
“It is worth noting that in a randomized clinical trial of probiotic treatment involving 60 AD patients, Akbari et al. demonstrated that after taking Lactobacillus and Bifidobacteria through fermented milk for 12 weeks, the patients’ cognition was significantly improved [153].”
The Immuno-Glial Connectome in Alzheimer’s Disease: Integrating Central and Peripheral Inflammatory Networks
Gopalakrishna, P. K., Nassir, C. M. N. C. M., Anandan, S., Hussan, F., Dandala, K. C. R., Sura, S., Jagadeesan, S., Moklas, M. A. M., Vishnumukkala, T., & Hein, Z. M. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01671-4 · Cited by 23
“…controlled trials (RCTs) in mild cognitive impairment (MCI) and early AD populations reported improved Mini-Mental State Examination (MMSE) scores and reductions in systemic inflammatory markers such as CRP and IL-6 following 12-week probiotic administration (Akbari et al. 2016; Xiao et al. 2025 ).”
Prebiotics and probiotics
Arruda, H. S., Geraldi, M. V., Cedran, M. F., Bicas, J. L., Maróstica, M. R., & Pastore, G. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823569-0.00006-0 · Cited by 20
Association of Yogurt and Dietary Supplements Containing Probiotic Consumption With All-Cause and Cause-Specific Mortality in US Adults: A Population-Based Cohort Study
Lin, P., Gui, X., Liang, Z., & Wang, T. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.803076 · Cited by 19
Gastrointestinal Changes and Alzheimer's Disease
Sohrabi, M., Sahu, B., Kaur, H., Hasler, W. A., Prakash, A. K., & Combs, C. K. (2022) · Current Alzheimer Research · doi:10.2174/1567205019666220617121255 · Cited by 18
The Role of Dietary Antioxidants and Their Potential Mechanisms in Alzheimer’s Disease Treatment
Knight, E., Geetha, T., Broderick, T. L., & Babu, J. R. (2023) · Metabolites · doi:10.3390/metabo13030438 · Cited by 20
The interlink between climate changes, gut microbiota, and aging processes
Gunawan, W. B., Abadi, M. N. P., Fadhillah, F. S., Nurkolis, F., & Pramono, A. (2023) · Human Nutrition & Metabolism · doi:10.1016/j.hnm.2023.200193 · Cited by 19

Authors: Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O. R., Hamidi, G. A., & Salami, M.
Affiliations: Kashan University of Medical Sciences (IR)
Corresponding author: Asemi, Zatollah
Salami, Mahmoud
ORCID: Asemi, Zatollah
Bahmani, Fereshteh
Kouchaki, Ebrahim
Tamtaji, Omid Reza
Hamidi, Gholam Ali
Salami, Mahmoud
Venue: Frontiers in Aging Neuroscience
Publisher: Frontiers Media SA
Published: 2016-11-10
Volume: 8
Pages: 256-256
ISSN: 1663-4365 (ISSN-L)
DOI: 10.3389/fnagi.2016.00256
PMC: PMC5105117
OpenAlex: W2549210709
Semantic Scholar: 7a1f1dc8208ef2c3d7013ce699ff50704195c24d
Cited by: 946
References: 60
Citations by year: 2026: 75 · 2025: 111 · 2024: 120 · 2023: 136 · 2022: 139 · 2021: 119 · 2020: 94 · 2019: 87 · 2018: 44 · 2017: 19
FWCI: 63.01
Type: journal article
Language: en
Update notices: expression_of_concern (2020-10-07)
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Aging Neuroscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Kashan University of Medical Sciences
Topics: Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: Alzheimer's disease, probiotics, probiotic milk, cognitive function, metabolic status, Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum, malondialdehyde, oxidative stress, C-reactive protein, insulin resistance, beta-cell function, triglycerides, Mini-Mental State Examination

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Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial

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