Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer's disease in bladder cancer patients
Alzheimer's disease (AD) affects one in ten people older than 65 years. Thus far, there is no cure or even disease-modifying treatment for this disease. The immune system is a major player in the pathogenesis of AD. Bacillus Calmette-Guérin (BCG), developed as a vaccine against tuberculosis, mo...
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| Veröffentlicht in: | PloS one 2019-11, Vol.14 (11), p.e0224433-e0224433 |
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| description | Alzheimer's disease (AD) affects one in ten people older than 65 years. Thus far, there is no cure or even disease-modifying treatment for this disease. The immune system is a major player in the pathogenesis of AD. Bacillus Calmette-Guérin (BCG), developed as a vaccine against tuberculosis, modulates the immune system and reduces recurrence of non-muscle invasive bladder cancer. Theoretical considerations suggested that treatment with BCG may decrease the risk of AD. We tested this hypothesis on a natural population of bladder cancer patients.
After removing all bladder cancer patients presenting with AD or developing AD within one-year following diagnosis of bladder cancer, we collected data on a total of 1371 patients (1134 males and 237 females) who were followed for at least one year after the diagnosis of bladder cancer. The mean age at diagnosis of bladder cancer was 68.1 years (SD 13.0). Adjuvant post-operative intra-vesical treatment with BCG was given to 878 (64%) of these patients. The median period post-operative follow-up was 8 years. During follow-up, 65 patients developed AD at a mean age of 84 years (SD 5.9), including 21 patients (2.4%) who had been treated with BCG and 44 patients (8.9%) who had not received BCG. Patients who had been treated with BCG manifested more than 4-fold less risk for AD than those not treated with BCG. The Cox proportional hazards regression model and the Kaplan-Meier analysis of AD free survival both indicated high significance: patients not treated with BCG had a significantly higher risk of developing AD compared to BCG treated patients (HR 4.778, 95%CI: 2.837-8.046, p = 4.08x10-9 and Log Rank Chi-square 42.438, df = 1, p = 7.30x10-11, respectively). Exposure to BCG did not modify the prevalence of Parkinson's disease, 1.9% in BCG treated patients and 1.6% in untreated (Fisher's Exact Test, p = 1).
Bladder cancer patients treated with BCG were significantly less likely to develop AD at any age than patients who were not so treated. This finding of a retrospective study suggests that BCG treatment might also reduce the incidence of AD in the general population. Confirmation of such effects of BCG in other retrospective studies would support prospective studies of BCG in AD. |
| doi_str_mv | 10.1371/journal.pone.0224433 |
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After removing all bladder cancer patients presenting with AD or developing AD within one-year following diagnosis of bladder cancer, we collected data on a total of 1371 patients (1134 males and 237 females) who were followed for at least one year after the diagnosis of bladder cancer. The mean age at diagnosis of bladder cancer was 68.1 years (SD 13.0). Adjuvant post-operative intra-vesical treatment with BCG was given to 878 (64%) of these patients. The median period post-operative follow-up was 8 years. During follow-up, 65 patients developed AD at a mean age of 84 years (SD 5.9), including 21 patients (2.4%) who had been treated with BCG and 44 patients (8.9%) who had not received BCG. Patients who had been treated with BCG manifested more than 4-fold less risk for AD than those not treated with BCG. The Cox proportional hazards regression model and the Kaplan-Meier analysis of AD free survival both indicated high significance: patients not treated with BCG had a significantly higher risk of developing AD compared to BCG treated patients (HR 4.778, 95%CI: 2.837-8.046, p = 4.08x10-9 and Log Rank Chi-square 42.438, df = 1, p = 7.30x10-11, respectively). Exposure to BCG did not modify the prevalence of Parkinson's disease, 1.9% in BCG treated patients and 1.6% in untreated (Fisher's Exact Test, p = 1).
Bladder cancer patients treated with BCG were significantly less likely to develop AD at any age than patients who were not so treated. This finding of a retrospective study suggests that BCG treatment might also reduce the incidence of AD in the general population. Confirmation of such effects of BCG in other retrospective studies would support prospective studies of BCG in AD.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0224433</identifier><identifier>PMID: 31697701</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Aged ; Aged, 80 and over ; Alzheimer Disease - complications ; Alzheimer Disease - drug therapy ; Alzheimer Disease - pathology ; Alzheimer's disease ; Animals ; Bacillus ; Bacillus Calmette-Guerin vaccine ; BCG ; BCG Vaccine - administration & dosage ; Biology and Life Sciences ; Bladder ; Bladder cancer ; Cancer ; Cancer therapies ; Clinical trials ; Cytokines ; Data collection ; Dementia ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Female ; Females ; Humans ; Immune system ; Incidence ; Invasiveness ; Kaplan-Meier Estimate ; Male ; Males ; Medical diagnosis ; Medical treatment ; Medicine and Health Sciences ; Mice ; Microbiota ; Middle Aged ; Movement disorders ; Muscles ; Mycobacterium bovis - genetics ; Mycobacterium bovis - immunology ; Neoplasm Recurrence, Local - drug therapy ; Neoplasm Recurrence, Local - pathology ; Neurodegenerative diseases ; Neurotoxicity ; Parkinson's disease ; Pathogenesis ; Pathology ; Population ; Regression analysis ; Regression models ; Research and Analysis Methods ; Risk ; Survival analysis ; Treatment Outcome ; Tuberculosis ; Urinary Bladder Neoplasms - complications ; Urinary Bladder Neoplasms - drug therapy ; Urinary Bladder Neoplasms - pathology ; Urology ; Vaccines</subject><ispartof>PloS one, 2019-11, Vol.14 (11), p.e0224433-e0224433</ispartof><rights>2019 Gofrit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Gofrit et al 2019 Gofrit et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-4e3bae5180890ae1db4b6ef9fcd4c22529c1368e03e860486180473764d428b63</citedby><cites>FETCH-LOGICAL-c526t-4e3bae5180890ae1db4b6ef9fcd4c22529c1368e03e860486180473764d428b63</cites><orcidid>0000-0002-3906-6993 ; 0000-0001-7297-3029 ; 0000-0001-8815-6488</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837488/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837488/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31697701$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gofrit, Ofer N</creatorcontrib><creatorcontrib>Klein, Benjamin Y</creatorcontrib><creatorcontrib>Cohen, Irun R</creatorcontrib><creatorcontrib>Ben-Hur, Tamir</creatorcontrib><creatorcontrib>Greenblatt, Charles L</creatorcontrib><creatorcontrib>Bercovier, Hervé</creatorcontrib><title>Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer's disease in bladder cancer patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Alzheimer's disease (AD) affects one in ten people older than 65 years. Thus far, there is no cure or even disease-modifying treatment for this disease. The immune system is a major player in the pathogenesis of AD. Bacillus Calmette-Guérin (BCG), developed as a vaccine against tuberculosis, modulates the immune system and reduces recurrence of non-muscle invasive bladder cancer. Theoretical considerations suggested that treatment with BCG may decrease the risk of AD. We tested this hypothesis on a natural population of bladder cancer patients.
After removing all bladder cancer patients presenting with AD or developing AD within one-year following diagnosis of bladder cancer, we collected data on a total of 1371 patients (1134 males and 237 females) who were followed for at least one year after the diagnosis of bladder cancer. The mean age at diagnosis of bladder cancer was 68.1 years (SD 13.0). Adjuvant post-operative intra-vesical treatment with BCG was given to 878 (64%) of these patients. The median period post-operative follow-up was 8 years. During follow-up, 65 patients developed AD at a mean age of 84 years (SD 5.9), including 21 patients (2.4%) who had been treated with BCG and 44 patients (8.9%) who had not received BCG. Patients who had been treated with BCG manifested more than 4-fold less risk for AD than those not treated with BCG. The Cox proportional hazards regression model and the Kaplan-Meier analysis of AD free survival both indicated high significance: patients not treated with BCG had a significantly higher risk of developing AD compared to BCG treated patients (HR 4.778, 95%CI: 2.837-8.046, p = 4.08x10-9 and Log Rank Chi-square 42.438, df = 1, p = 7.30x10-11, respectively). Exposure to BCG did not modify the prevalence of Parkinson's disease, 1.9% in BCG treated patients and 1.6% in untreated (Fisher's Exact Test, p = 1).
Bladder cancer patients treated with BCG were significantly less likely to develop AD at any age than patients who were not so treated. This finding of a retrospective study suggests that BCG treatment might also reduce the incidence of AD in the general population. Confirmation of such effects of BCG in other retrospective studies would support prospective studies of BCG in AD.</description><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - complications</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Bacillus</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>BCG</subject><subject>BCG Vaccine - administration & dosage</subject><subject>Biology and Life Sciences</subject><subject>Bladder</subject><subject>Bladder cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Clinical trials</subject><subject>Cytokines</subject><subject>Data collection</subject><subject>Dementia</subject><subject>Diagnosis</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Females</subject><subject>Humans</subject><subject>Immune system</subject><subject>Incidence</subject><subject>Invasiveness</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Males</subject><subject>Medical diagnosis</subject><subject>Medical treatment</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Microbiota</subject><subject>Middle Aged</subject><subject>Movement disorders</subject><subject>Muscles</subject><subject>Mycobacterium bovis - genetics</subject><subject>Mycobacterium bovis - immunology</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neurodegenerative diseases</subject><subject>Neurotoxicity</subject><subject>Parkinson's disease</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Population</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Research and Analysis Methods</subject><subject>Risk</subject><subject>Survival analysis</subject><subject>Treatment Outcome</subject><subject>Tuberculosis</subject><subject>Urinary Bladder Neoplasms - complications</subject><subject>Urinary Bladder Neoplasms - drug therapy</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urology</subject><subject>Vaccines</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptks1u1DAUhSMEoqXwBggssaAsZrB9HcfZILUjGCpVYgNry7FvOh45cbATUHkjnoMXI9OZVi1i5b_vHt9zdYriJaNLBhV7v41T6k1YDrHHJeVcCIBHxTGrgS8kp_D43v6oeJbzltISlJRPiyNgsq4qyo6L_txYH8KUycqEDscRF-vpz-_ke3J6vlq_I-MGkxmuSYg_MeXdkfjeeoe9RRJbchZ-bdB3mN5m4nxGk3cAaYJxDhOxZuYSGczosR_z8-JJa0LGF4f1pPj26ePX1efF5Zf1xerscmFLLseFQGgMlkxRVVODzDWikdjWrXXCcl7y2jKQCimgklQoOZOigkoKJ7hqJJwUr_e6Q4hZH0aVNQfGq7qkDGbiYk-4aLZ6SL4z6VpH4_XNRUxX2qTR24Da8Qqkqy3SkotagEIzT1s6U7bAHeWz1ofDb1PTobOz02TCA9GHL73f6Kv4Q0sFlVBqFjg9CKT4fcI86s5niyGYHuN00zeA5KWqZvTNP-j_3Yk9ZVPMOWF71wyjehef2yq9i48-xGcue3XfyF3RbV7gL-oAwvo</recordid><startdate>20191107</startdate><enddate>20191107</enddate><creator>Gofrit, Ofer N</creator><creator>Klein, Benjamin Y</creator><creator>Cohen, Irun R</creator><creator>Ben-Hur, Tamir</creator><creator>Greenblatt, Charles L</creator><creator>Bercovier, Hervé</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3906-6993</orcidid><orcidid>https://orcid.org/0000-0001-7297-3029</orcidid><orcidid>https://orcid.org/0000-0001-8815-6488</orcidid></search><sort><creationdate>20191107</creationdate><title>Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer's disease in bladder cancer patients</title><author>Gofrit, Ofer N ; Klein, Benjamin Y ; Cohen, Irun R ; Ben-Hur, Tamir ; Greenblatt, Charles L ; Bercovier, Hervé</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-4e3bae5180890ae1db4b6ef9fcd4c22529c1368e03e860486180473764d428b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Age</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - complications</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>Bacillus</topic><topic>Bacillus Calmette-Guerin vaccine</topic><topic>BCG</topic><topic>BCG Vaccine - administration & dosage</topic><topic>Biology and Life Sciences</topic><topic>Bladder</topic><topic>Bladder cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Clinical trials</topic><topic>Cytokines</topic><topic>Data collection</topic><topic>Dementia</topic><topic>Diagnosis</topic><topic>Disease Progression</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Females</topic><topic>Humans</topic><topic>Immune system</topic><topic>Incidence</topic><topic>Invasiveness</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Males</topic><topic>Medical diagnosis</topic><topic>Medical treatment</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Microbiota</topic><topic>Middle Aged</topic><topic>Movement disorders</topic><topic>Muscles</topic><topic>Mycobacterium bovis - genetics</topic><topic>Mycobacterium bovis - immunology</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Neurodegenerative diseases</topic><topic>Neurotoxicity</topic><topic>Parkinson's disease</topic><topic>Pathogenesis</topic><topic>Pathology</topic><topic>Population</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Research and Analysis Methods</topic><topic>Risk</topic><topic>Survival analysis</topic><topic>Treatment Outcome</topic><topic>Tuberculosis</topic><topic>Urinary Bladder Neoplasms - complications</topic><topic>Urinary Bladder Neoplasms - drug therapy</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urology</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gofrit, Ofer N</creatorcontrib><creatorcontrib>Klein, Benjamin Y</creatorcontrib><creatorcontrib>Cohen, Irun R</creatorcontrib><creatorcontrib>Ben-Hur, Tamir</creatorcontrib><creatorcontrib>Greenblatt, Charles L</creatorcontrib><creatorcontrib>Bercovier, Hervé</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gofrit, Ofer N</au><au>Klein, Benjamin Y</au><au>Cohen, Irun R</au><au>Ben-Hur, Tamir</au><au>Greenblatt, Charles L</au><au>Bercovier, Hervé</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer's disease in bladder cancer patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-11-07</date><risdate>2019</risdate><volume>14</volume><issue>11</issue><spage>e0224433</spage><epage>e0224433</epage><pages>e0224433-e0224433</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Alzheimer's disease (AD) affects one in ten people older than 65 years. Thus far, there is no cure or even disease-modifying treatment for this disease. The immune system is a major player in the pathogenesis of AD. Bacillus Calmette-Guérin (BCG), developed as a vaccine against tuberculosis, modulates the immune system and reduces recurrence of non-muscle invasive bladder cancer. Theoretical considerations suggested that treatment with BCG may decrease the risk of AD. We tested this hypothesis on a natural population of bladder cancer patients.
After removing all bladder cancer patients presenting with AD or developing AD within one-year following diagnosis of bladder cancer, we collected data on a total of 1371 patients (1134 males and 237 females) who were followed for at least one year after the diagnosis of bladder cancer. The mean age at diagnosis of bladder cancer was 68.1 years (SD 13.0). Adjuvant post-operative intra-vesical treatment with BCG was given to 878 (64%) of these patients. The median period post-operative follow-up was 8 years. During follow-up, 65 patients developed AD at a mean age of 84 years (SD 5.9), including 21 patients (2.4%) who had been treated with BCG and 44 patients (8.9%) who had not received BCG. Patients who had been treated with BCG manifested more than 4-fold less risk for AD than those not treated with BCG. The Cox proportional hazards regression model and the Kaplan-Meier analysis of AD free survival both indicated high significance: patients not treated with BCG had a significantly higher risk of developing AD compared to BCG treated patients (HR 4.778, 95%CI: 2.837-8.046, p = 4.08x10-9 and Log Rank Chi-square 42.438, df = 1, p = 7.30x10-11, respectively). Exposure to BCG did not modify the prevalence of Parkinson's disease, 1.9% in BCG treated patients and 1.6% in untreated (Fisher's Exact Test, p = 1).
Bladder cancer patients treated with BCG were significantly less likely to develop AD at any age than patients who were not so treated. This finding of a retrospective study suggests that BCG treatment might also reduce the incidence of AD in the general population. Confirmation of such effects of BCG in other retrospective studies would support prospective studies of BCG in AD.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31697701</pmid><doi>10.1371/journal.pone.0224433</doi><orcidid>https://orcid.org/0000-0002-3906-6993</orcidid><orcidid>https://orcid.org/0000-0001-7297-3029</orcidid><orcidid>https://orcid.org/0000-0001-8815-6488</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-11, Vol.14 (11), p.e0224433-e0224433 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2312795013 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Age Aged Aged, 80 and over Alzheimer Disease - complications Alzheimer Disease - drug therapy Alzheimer Disease - pathology Alzheimer's disease Animals Bacillus Bacillus Calmette-Guerin vaccine BCG BCG Vaccine - administration & dosage Biology and Life Sciences Bladder Bladder cancer Cancer Cancer therapies Clinical trials Cytokines Data collection Dementia Diagnosis Disease Progression Disease-Free Survival Female Females Humans Immune system Incidence Invasiveness Kaplan-Meier Estimate Male Males Medical diagnosis Medical treatment Medicine and Health Sciences Mice Microbiota Middle Aged Movement disorders Muscles Mycobacterium bovis - genetics Mycobacterium bovis - immunology Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - pathology Neurodegenerative diseases Neurotoxicity Parkinson's disease Pathogenesis Pathology Population Regression analysis Regression models Research and Analysis Methods Risk Survival analysis Treatment Outcome Tuberculosis Urinary Bladder Neoplasms - complications Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - pathology Urology Vaccines |
| title | Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer's disease in bladder cancer patients |
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