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

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.

AI snapshot

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

  • Findingown data

    12 weeks probiotic consumption in AD patients had favorable effects on markers of insulin metabolism.

    “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.”
    Quote in the paperSubstantial claim
  • Findingown data

    No side effects were reported following probiotic administration in Alzheimer's disease patients throughout the study.

    “No side effects were reported following administration with probiotic in AD patients throughout the study.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Probiotic supplementation decreased plasma MDA levels in AD patients.

    “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.”
    Quote in the paperSubstantial claim
  • Findingown data

    12 weeks probiotic consumption in AD patients had favorable effects on VLDL levels.

    “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.”
    Quote in the paperSubstantial claim
  • Findingown data

    Probiotic treatment was ineffective on FPG in AD patients.

    “However, the pobiotic treatment was inefective on other biomarkers of oxidative stress and inflammation, FPG, and other lipid profiles.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 35

  • May combine two claims.

    Findingown data

    Twelve weeks of intervention resulted in an improvement in MMSE score in the probiotic group (+27.90% ± 8.07) compared with the control group (−5.03% ± 3.00), and the difference was statistically significant (P < 0.001).

    “Twelve weeks intervention resulted in an improvement in MMSE score in the probiotic group (+27.90% ± 8.07) compared to their control counterparts (−5.03% ± 3.00). The difference between the two groups of testing was statistically significant (P <0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The HOMA-B index was reduced in the probiotic group (+3.45% ± 10.91) compared with the control group (+75.62% ± 23.18), with a significant difference (P = 0.001).

    “The probiotic treatment considerably reduced the HOMA-B index (+3.45% ± 10.91) in the probiotic compared to the control (+75.62% ± 23.18) patients leading to a significant variation between the two groups (P = 0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Probiotic supplementation was ineffective on fasting plasma glucose; changes were 3.41% ± 2.12 mg/dl in the probiotic group and 4.50% ± 4.39 mg/dl in the control group.

    “On the other hand, the probiotic supplementation was ineffective on the FBP; the changes are (3.41% ± 2.12) and (4.50% ± 4.39) mg/dl in the probiotic and control groups, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Changes in other biomarkers of oxidative stress and inflammation, fasting plasma glucose, and other lipid profiles were negligible.

    “however, the changes in other biomarkers of oxidative stress and inflammation, FPG and other lipid profiles are negligible.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The HOMA-IR index decreased in the probiotic group (+28.84% ± 13.34) compared with the control group (+76.95% ± 24.60), with a significant difference (P = 0.002).

    “HOMH-IR index decreased in the probiotic group (+28.84% ± 13.34) compared to their control counterparts (+76.95% ± 24.60, P = 0.002).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Changes in high-sensitivity C-reactive protein were −17.61% ± 3.70 in the probiotic group and +45.26% ± 3.50 μg/ml in the control group, with a significant difference (P < 0.001).

    “The changes in hs-CRP were −17.61% ± 3.70 and +45.26% ± 3.50 μg/ml in the probiotic and control groups, respectively (P <0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The QUICKI level was significantly increased in the probiotic subjects (−1.83% ± 1.26) compared with the control subjects (−4.66% ± 1.70), with a significant difference (P = 0.006).

    “The QUICKI level was significantly (P = 0.006) increased in the probiotic subjects (−1.83% ± 1.26) in comparison to their control counterparts (−4.66% ± 1.70).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Informed consent was received from all patients before beginning the study.

    “Informed consent was received from all patients before beginning the study.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The Mini-Mental State Examination was used to assess cognition in the Alzheimer's disease subjects.

    “The MMSE was used to assess cognition in the AD subjects (Folstein et al., 1975).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Folstein et al., 1975 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In the authors' previous work, probiotics efficiently reversed impaired spatial learning and memory as well as synaptic transmission in diabetes mellitus.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Davari et al., 2013 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Other brain-related disorders such as multiple sclerosis and stress are also influenced by probiotics.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kouchaki et al., 2016 source

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    • cites Liang et al., 2015 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The trial was performed in accordance with the Declaration of Helsinki.

    “This trial was performed in accordance with the Declaration of Helsinki.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The research was approved by the ethics committee of Kashan University of Medical Sciences and was registered in the Iranian website for registration of clinical trials (IRCT201511305623N60).

    “The research was approved by the ethics committee of Kashan University of Medical Sciences (KUMS) and was registered in the Iranian website for registration of clinical trials (http://www.irct.ir) IRCT201511305623N60.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study was a 12-week randomized, double-blind, and controlled clinical trial.

    “This study was a 12-week randomized, double-blind, and controlled clinical trial.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increased biomarkers of oxidative stress, inflammation and chronic neuroinflammation are associated with many neurodegenerative disorders of the central nervous system, including Alzheimer's disease.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Furman et al., 2016 source

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    • cites Leszek et al., 2016 source

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  • Classified as probably not a substantial claim.

    Study design and conductown data

    Participants were randomly divided into two groups to receive either milk or milk containing a mixture of probiotics for 12 weeks.

    “The participants were then randomly divided into two groups to receive either milk (control group, n = 30: 24 females and 6 males) or milk containing a mixture of probiotics (probiotic group, n = 30: 24 females and 6 males) for 12 weeks.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Intestinal dysbiosis in germ-free animals, bacterial infection with an enteric pathogen, and administration of probiotics can modulate cognitive behaviors including learning and memory.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gareau, 2014 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    At the onset of the study, all subjects were matched for disease severity based on gender, BMI, and age.

    “At the onset of the study, all subjects were matched for disease severity based on gender, BMI, and age.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All inter- and intra-assay coefficients of variation for nitric oxide, total antioxidant capacity, glutathione, malondialdehyde, fasting plasma glucose, and lipid profiles were lower than 5%.

    “All inter- and intra-assay CVs for NO, TAC, GSH, MDA, FPG, and lipid profiles were lower than 5%.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Alzheimer's disease patients are predisposed to complications including increased oxidative stress, morbidity, mortality, microvascular disease, dyslipidemia, and insulin resistance.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Sultana et al., 2011 source

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    • cites Schelke et al., 2016 source

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    • cites Sridhar et al., 2015 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Missing values were treated based on the Last-Observation-Carried-Forward method.

    “Missing values were treated based on Last-Observation-Carried-Forward method (LOCF) (Lachin, 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lachin, 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Probiotics intake may improve markers of insulin metabolism and lipid profiles by reducing cytokines and suppressing NF-κB pathway and gut microbiota-SCFA-hormone axis.

    “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).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Shi et al., 2006 source

      Not checked in the free run.

    • cites Yadav et al., 2013 source

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  • May combine two claims.

    Study design and conductown data

    Mean age, height, weight, and BMI at baseline and end of trial were not statistically different between the two groups.

    “Mean age, height, weight, and BMI at baseline and end of trial were not statistically different between the two groups (Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Consumption of symbiotic bread containing Lactobacillus sporogenes for 8 weeks decreased serum triglyceride and VLDL concentrations in type 2 diabetes patients.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shakeri et al., 2014 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    High lipid levels could be one of the risk factors for AD.

    “Accordingly, high lipid levels could be one of the risk factors for AD (Reitz et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Reitz et al., 2010 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Oxidative stress is a frequently observed feature of AD, although its pathological significance is not understood.

    “Oxidative stress is a frequently observed feature of AD, although its pathological significance is not understood (Selvarajah et al., 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Selvarajah et al., 2011 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    During the study, 4 out of 30 patients in the two groups died and a total of 52 subjects completed the experiments.

    “During the study 4 out of 30 patients in the two groups were died and a total of 52 subjects [control (n = 26) and probiotic (n = 26)] completed the experiments (Figure 1).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Randomization assignment was conducted using computer-generated random numbers.

    “Randomization assignment was conducted using computer-generated random numbers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The trial was registered at http://www.irct.ir: IRCT201511305623N60.

    “http://www.irct.ir: IRCT201511305623N60.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxidative stress acts as a vehicle for deposition and accumulation of amyloid β in AD through production of reactive oxygen species.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kim et al., 2015 source

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    Study design and conductreasoning

    Because the analysis was based on the intention-to-treat principle, all 60 patients were included in the final analysis.

    “However, as the analysis was based on the ITT principle, all 60 patients were included in the final analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Analyses were controlled for baseline values of biochemical parameters, age, and baseline BMI, and this adjustment indicated no considerable changes in the findings.

    “Therefore, we controlled the analyses for the baseline values of biochemical parameters, age, and baseline BMI. Nevertheless, this adjustment indicated no considerable changes in our findings (Data not shown).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The randomized allocation sequence, enrolling subjects, and allocating them to interventions were conducted by trained staff at the Welfare Organizations.

    “The randomized allocation sequence, enrolling subjects and allocating them to interventions were conducted by a trained staff at the Welfare Organizations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    6 weeks probiotic treatment caused no significant change in inflammatory factors of diabetic patients.

    “For example, it was reported that 6 weeks probiotic treatment caused no significant change in inflammatory factors of diabetic patients (Mazloom et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mazloom et al., 2013

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  • May combine two claims.

    Premisecitation

    Dysfunctions in GABA-signaling are linked to anxiety, depression, defects in synaptogenesis, and cognitive impairments.

    “Dysfunctions in GABA-signaling are linked to anxiety and depression, defects in synaptogenesis and cognitive impairments (Aziz et al., 2013; Mitew et al., 2013).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Aziz et al., 2013 source

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    • cites Mitew et al., 2013 source

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    Premisecitation

    Glutamatergic NMDA receptors are involved in excitatory neurotransmission engaged in neural circuits of learning and memory.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Talaei et al., 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    8 weeks consumption of capsules containing 108 CFU/g of L. casei by rheumatoid arthritis patients displayed no significant changes in MDA and TAC levels.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Vaghef-Mehrabany et al., 2015 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    8 weeks consumption of yogurt enriched by L. acidophilus, Bifidobacterium langum, and L. casei decreased inflammatory cytokines in overweight people.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zarrati et al., 2014 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction.

    “Some evidence from clinical studies support the fact that abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction (Wang et al., 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang et al., 2014 source

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  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Randomization and allocation were concealed from the researchers and individuals until the final analyses were completed.

    “Randomization and allocation were concealed from the researchers and individuals until the final analyses were completed.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Analyses were conducted based on an intention-to-treat principle.

    “Analyses were conducted based on an intention-to-treat (ITT) principle.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Germ-free animals show decreased BDNF and reduced expression of some NMDA receptor subunits.

    “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).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Sudo et al., 2004 source

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    • cites Salami et al., 2000 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Brain insulin resistance may take a role in AD.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cervellati et al., 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Oxidative stress may decrease the activity of α-secretase, promoting β and γ-secretase and increasing Aβ production.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tan et al., 2013 source

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  • May combine two claims.

    Interpretationown data

    Probiotic administration for 12 weeks has favorable effects on MMSE score, malondialdehyde, high-sensitivity C-reactive protein, markers of insulin metabolism, and triglyceride levels in Alzheimer's disease patients.

    “The current study demonstrated that the probiotic administration for 12 weeks has favorable effects on MMSE score, MDA, hs-CRP, markers of insulin metabolism and triglycerides levels of the AD patients;”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients.

    “Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients (Ma et al., 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ma et al., 2015

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  • May combine two claims.

    Interpretationreasoning

    Both dysbiosis and probiotic treatment could have profound effects on CNS functions because the microbiota-gut-brain axis conduits some of its main actions through nerve pathways.

    “Altogether, since the microbiota-gut-brain axis conduits some of its main actions through nerve pathways both dysbiosis and probiotic treatment could have profound effects on the CNS functions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In a meta-analysis, probiotic treated subjects had reduced HOMA-IR and insignificant FGP.

    “Consistently, in a meta-analysis study, Kasińska and Drzewoski (2015) reported a reduced HOMA-IR and insignificant FGP in probiotic treated subjects.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kasińska and Drzewoski, 2015

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A significant reduction in MDA levels was reported in type 2 diabetic patients after consuming probiotic yogurt.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ejtahed et al., 2012 source

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    Study design and conductnone given

    The authors declare no conflict of interest.

    “The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.”
    Quote in the paperNot a substantial claim
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

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A probiotic mixture containing B. longum and different Lactobacillus strains positively affected cognitive function and metabolic status in Alzheimer's disease patients.

    “Recently, a probiotic mixture containing B. longum and different Lactobacillus strains positively affected cognitive function and metabolic status in Alzheimer's disease patients (Akbari et al., 2016).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Akbari et al., 2016

    The Intervention section lists three Lactobacillus strains, but the Bifidobacterium strain is B. bifidum, not B. longum. The Results and Discussion report improved MMSE scores and favorable changes in some metabolic markers in patients with Alzheimer’s disease, supporting the reported effects but not the mixture as described. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Clinical trials have shown that probiotic supplementation can improve cognitive function and reduce inflammation in AD patients.

    “Clinical trials have shown that probiotic supplementation can improve cognitive function and reduce inflammation in AD patients218.”

    From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [218]

  • Probiotics could improve cognitive, sensory and emotional function in AD patients.

    “and could improve cognitive, sensory and emotional function in AD patients (Akbari et al. 2016).”

    From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Akbari et al. 2016

  • A probiotic fermented milk drink containing L. acidophilus, L. casei, B. bifidum, and L. fermentum improves cognitive function in AD patients.

    “while the assumption of a probiotic fermented milk drink containing L. acidophilus, L. casei, B. bifidum, and L. fermentum improves cognitive function in AD patients [323].”

    From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [323]

  • Probiotics have been shown to improve cognitive symptoms and biochemical markers in participants with various dysbiosis-related disorders, including Alzheimer's disease, fibromyalgia, and irritable bowel syndrome.

    “Probiotics have been shown to improve cognitive symptoms and biochemical markers in participants with various dysbiosis-related disorders, including Alzheimer’s disease (476), fibromyalgia (477, 478), and irritable bowel syndrome (IBS) (479).”

    From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [476]

Cites

2 retracted

Flagged first, then by citations

1 of the 60 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

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

Cited by

Sorted by citations

Related

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
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
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
  • Health Sciences › Medicine › Physiology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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