OBJECTIVES: This study presents results of our randomized clinical trial studying the effect of human probiotics on memory and psychological and physical measures following our study protocol registered at clinicaltrials.gov NCT05051501 and described in detail in our previous paper. METHODS: Community dwelling participants aged between 55 and 80 years were randomly assigned to receive a single dose of 106 colony-forming units of human Streptococcus thermophilus GH, Streptococcus salivarius GH NEXARS, Lactobacilus plantarum GH, and Pediococcus pentosaceus GH or placebo. A cross-over design allowed each group to receive probiotics and placebo for 3 months each in reverse order. A small subset of participants was examined online due to the COVID-19 pandemic. After 6 months a small number of volunteers were additionally assessed after 2 months without any intervention. Primary outcome measures included changes in cognitive functions assessed using brief tests and a neuropsychological battery and changes in mood assessed using validated questionnaires. Secondary outcome measures included changes in self-report and subjective measures using depression and anxiety questionnaires, seven visual analog scales of subjective feelings (memory, digestion, etc.), and physical performance. RESULTS: At baseline, the probiotic-placebo group A (n = 40, age 69 ± 7 years, education 16 ± 3 years, 63% females, body mass index 28.5 ± 6, subjective memory complaint in 43%) did not differ from the placebo-probiotic group B (n = 32) in any of the sociodemographic characteristics and evaluated measures including cognitive status. At follow-up visits after 3, 6, and 8 months, no cross-sectional differences in any of the measures were found between the groups except worse sentence recall of the ALBA test after 3 months of probiotic use. Score changes were not observed for all cognitive tests but one in any group between visits 1 and 3 and between visits 3 and 6. The only change was observed for the TMT B test after the first three months but no change was observed after the second three months. CONCLUSION: The treatment with human probiotics and prebiotics did not improve cognitive, affective, or physical measures in community-dwelling individuals with normal or mildly impaired cognitive functions. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT05051501.

1st Faculty of Medicine Charles University Prague Czechia

Department of Neurology 3rd Faculty of Medicine Charles University Prague Czechia

Department of Neurology Faculty Hospital Královské Vinohrady Prague Czechia

National Institute of Mental Health Klecany Czechia

Zobrazit více v PubMed

American Psychiatric Association (2015). “Diagnostic and statistical manual of mental disorders (DSM-5®)” in book in Czech: Diagnostický a statistický manuál duševních poruch. 5th ed (Praha: Hogrefe – Testcentrum; ), 633–675.

Bartos A. (2016). Do not test but PICNIR (ENTERTAIN) - written intentional naming of pictures and their recall as a brief cognitive test [article in Czech Netestuj, ale POBAV - písemné záměrné pojmenování obrázků a jejich vybavení jako krátká kognitivní zkouška]. Cesk. Slov. Neurol. N. 79, 671–679.

Bartos A. (2019). Two original Czech tests for memory evaluation in three minutes – amnesia light and brief assessment (ALBA) [article in Czech Dvě původní české zkoušky k vyšetření paměti za tři minuty – amnesia light and brief assessment (ALBA)]. Cesk. Slov. Neurol. N. 82, 420–429. doi: 10.14735/amcsnn2019420 DOI

Bartos A. (2021). ALBA and PICNIR tests used for simultaneous examination of two patients with dementia and their adult children. Cesk. Slov. Neurol. 84/117, 583–586. doi: 10.48095/cccsnn2021583 DOI

Bartos A., Diondet S. (2020). Amnesia light and brief assessment (ALBA) test – the second version and repeated examinations [article in Czech test amnesia light and brief assessment (ALBA) – druhá verze a opakovaná vyšetření]. Cesk. Slov. Neurol. N. 82, 535–543. doi: 10.14735/amcsnn2020535 DOI

Bartos A., Diondet S. (2023). Sensitive amnesia light and brief assessment (ALBA) is a valid three-minute test of four tasks indicative of mild cognitive deficits. Neurologia (in press).

Bartos A., Janoušek M., Petroušová R., Hohinová M. (2016). Three times of the clock drawing test rated with BaJa scoring in patients with early Alzheimer’s disease [article in Czech Tři časy Testu kreslení hodin hodnocené BaJa skórováním u časné Alzheimerovy nemoci]. Cesk. Slov. Neurol. N. 112, 406–412.

Bartos A., Krejcova M. (2022). Development of the electronic memory test for the elderly (ALBAV) [article in Czech Vývoj elektronického testu paměti pro starší osoby (ALBAV)]. Cesk. Slov. Neurol. N. 85, 369–374. doi: 10.48095/cccsnn2022369 DOI

Bartos A., Krejcova M. (2023). Validation of the electronic memory test ALBAV [article in Czech Validizace elektronického testu paměti ALBAV]. Cesk. Slov. Neurol. N. 86/119, 49–56. doi: 10.48095/cccsnn202349 DOI

Bartos A., Polanská H. (2021). Correct and incorrect naming of pictures for the more demanding written Picture naming and immediate recall test (door PICNIR) [article in Czech Správná a chybná pojmenování obrázků pro náročnější test písemného Pojmenování obrázků a jejich vybavení (dveřní POBAV)]. Cesk. Slov. Neurol. N. 84, 151–163. doi: 10.48095/cccsnn2021151 DOI

Bartos A., Weinerova J., Diondet S., Vales K. (2022). Effect of human probiotics on memory, psychological and biological measures in elderly: a study protocol of bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge biota). Front. Aging Neurosci. 14:996234. doi: 10.3389/fnagi.2022.996234 PubMed DOI PMC

Beck A. T., Epstein N., Brown G., Steer R. A. (1988). An inventory for measuring clinical anxiety: psychometric properties. J. Consult. Clin. Psychol. 56, 893–897. doi: 10.1037//0022-006x.56.6.893 PubMed DOI

Beck A. T., Steer R. A., Brown G. K. (1996). Beck depression inventory (BDI-II), 10. London: Pearson.

Benton D., Williams C., Brown A. (2007). Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61, 355–361. doi: 10.1038/sj.ejcn.1602546 PubMed DOI

Białecka-Dębek A., Granda D., Szmidt M. K., Zielińska D. (2021). Gut microbiota, probiotic interventions, and cognitive function in the elderly: a review of current knowledge. Nutrients 13:2514. doi: 10.3390/nu13082514 PubMed DOI PMC

Bridel C., van Wieringen W. N., Zetterberg H., Tijms B. M., Teunissen C. E., the NFL Group et al. . (2019). Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis. JAMA Neurol. 76, 1035–1048. doi: 10.1001/jamaneurol.2019.1534 PubMed DOI PMC

Chung Y.-C., Jin H.-M., Cui Y.-K., Dal J., Jin P., Jong-Li J., et al. . (2014). Fermented milk of lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J. Funct. Foods 10, 465–474. doi: 10.1016/j.jff.2014.07.007 DOI

Dvořáková T., Bušková J., Bartoš A. (2022). Neurological symptoms associated with COVID-19 based on a nation-wide online survey [article in Czech Neurologické příznaky asociované s onemocněním COVID-19 podle celostátního online průzkumu]. Cesk. Slov. Neurol. N. 85, 220–227. doi: 10.48095/cccsnn2022220 DOI

Fialová L., Nosková L., Kalousová M., Zima T., Uher T., Bartoš A. (2022). Analytical and pre-analytical aspects of neurofilament light chain determination in biological fluids [article in Czech Analytické a preanalytické aspekty stanovení lehkých řetězců neurofilament v biologických tekutinách]. Cesk. Slov. Neurol. N. 85, 11–16. doi: 10.48095/cccsnn202211 DOI

Inoue T., Kobayashi Y., Mori N., Sakagawa M., Xiao J.-Z., Moritani T., et al. . (2018). Effect of combined bifidobacteria supplementation and resistance training on cognitive function, body composition and bowel habits of healthy elderly subjects. Benef. Microbes. 9, 843–853. doi: 10.3920/BM2017.0193 PubMed DOI

Jekel K., Damian M., Wattmo C., Hausner L., Bullock R., Connelly P. J., et al. . (2015). Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review. Alzheimers Res. Ther. 7:17. doi: 10.1186/s13195-015-0099-0 PubMed DOI PMC

Kobayashi Y., Kuhara T., Oki M., Xiao J. (2019). Effects of bifidobacterium breve a1 on the cognitive function of older adults with memory complaints: a randomised, double-blind, placebo-controlled trial. Benef. Microbes. 10, 511–520. doi: 10.3920/BM2018.0170 PubMed DOI

Krüger J. F., Hillesheim E., Pereira A. C. S. N., Camargo C. Q., Rabito E. I. (2021). Probiotics for dementia: a systematic review and meta-analysis of randomized controlled trials. Nutr. Rev. 79, 160–170. doi: 10.1093/nutrit/nuaa037 PubMed DOI

Lezak M. D., Howieson D. B., Bigler E. D., Tranel D. (2012). Neuropsychological assessment. New York, NY: Oxford University Press.

Louzada E. R., Ribeiro S. M. L. (2020). Synbiotic supplementation, systemic inflammation, and symptoms of brain disorders in elders: a secondary study from a randomized clinical trial. Nutr. Neurosci. 23, 93–100. doi: 10.1080/1028415X.2018.1477349 PubMed DOI

Lv T., Ye M., Luo F., Hu B., Wang A., Chen J., et al. . (2021). Probiotics treatment improves cognitive impairment in patients and animals: a systematic review and meta-analysis. Neurosci. Biobehav. Rev. 120, 159–172. doi: 10.1016/j.neubiorev.2020.10.027 PubMed DOI

Ohsawa K., Nakamura F., Uchida N., Mizuno S., Yokogoshi H. (2018). Lactobacillus helveticus-fermented milk containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) improves cognitive function in healthy middle-aged adults: a randomised, double-blind, placebo-controlled trial. Int. J. Food Sci. Nutr. 69, 369–376. doi: 10.1080/09637486.2017.1365824 PubMed DOI

Pfeffer R. I., Kurosaki T. T., Harrah C., Jr., Chance J. M., Filos S. (1982). Measurement of functional activities in older adults in the community. J. Gerontol. 37, 323–329. doi: 10.1093/geronj/37.3.323 PubMed DOI

Polanská H., Bartoš A. (2022). Telemedicine assessments by remote versions of ALBA, POBAV and ACE-III tests [article in Czech Telemedicínské vyšetření kognitivními testy ALBA, POBAV a ACE-III]. Cesk. Slov. Neurol. N. 85, 296–305. doi: 10.48095/cccsnn2022296 DOI

Preiss M., Bartos A., Čermáková R., Nondek M., Benešová M., Rodriguez M., et al. . (2012). “Neuropsychological battery of the psychiatric Prague center: clinical examinations of major cognitive functions” in A book in Czech: Neuropsychologická baterie Psychiatrického centra Praha: Klinické vyšetření základních kognitivních funkcí (3). 3rd ed (Praha: Psychiatrické centrum Praha; )

Ruiz-Gonzalez C., Cardona D., Rodriguez-Arrastia M., Ropero-Padilla C., Rueda-Ruzafa L., Carvajal F., et al. . (2022). Effects of probiotics on cognitive and emotional functions in healthy older adults: protocol for a double-blind randomized placebo-controlled crossover trial. Res. Nurs. Health 45, 274–286. doi: 10.1002/nur.22209 PubMed DOI

Sánchez-de-Lara-Sánchez S., Sánchez-Pérez A. M. (2022). Probiotics treatment can improve cognition in patients with mild cognitive impairment: a systematic review. J. Alzheimers Dis. 89, 1173–1191. doi: 10.3233/JAD-220615 PubMed DOI

Tahmasbi F., Mirghafourvand M., Shamekh A., Mahmoodpoor A., Sanaie S. (2022). Effects of probiotic supplementation on cognitive function in elderly: a systematic review and Meta-analysis. Aging Ment. Health 26, 1778–1786. doi: 10.1080/13607863.2021.1966743 PubMed DOI

Trejo-Castro A. I., Carrion-Alvarez D., Martinez-Torteya A., Rangel-Escareño C. (2022). A bibliometric review on gut microbiome and Alzheimer's disease between 2012 and 2021. Front. Aging Neurosci. 14:804177. doi: 10.3389/fnagi.2022.804177 PubMed DOI PMC

Wallace C. J. K., Milev R. (2017). The effects of probiotics on depressive symptoms in humans: a systematic review. Ann. General Psychiatry 16:14. doi: 10.1186/s12991-017-0138-2 PubMed DOI PMC

Xiang S., Ji J. L., Li S., Cao X. P., Xu W., Tan L., et al. . (2022). Efficacy and safety of probiotics for the treatment of Alzheimer's disease, mild cognitive impairment, and Parkinson's disease: a systematic review and meta-analysis. Front. Aging Neurosci. 14:730036. doi: 10.3389/fnagi.2022.730036 PubMed DOI PMC

Yesavage J. A., Brink T. L., Rose T. L., Lum O., Huang V., Adey M., et al. . (1982). Development and validation of a geriatric depression screening scale: a preliminary report. J. Psychiatr. Res. 17, 37–49. doi: 10.1016/0022-3956(82)90033-4 PubMed DOI

Serum neurofilament light chain in response to probiotics in bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota)

Zobrazit více v PubMed

ClinicalTrials.gov
NCT05051501