Tetrahydroaminoacridine–Lecithin Combination Treatment in Patients with Intermediate-Stage Alzheimer's Disease: Results of a Canadian Double-Blind, Crossover, Multicenter Study
We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placeb...
Gespeichert in:
| Veröffentlicht in: | The New England journal of medicine 1990-05, Vol.322 (18), p.1272-1276 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1276 |
|---|---|
| container_issue | 18 |
| container_start_page | 1272 |
| container_title | The New England journal of medicine |
| container_volume | 322 |
| creator | Gauthier, Louise Gauthier, Serge Bouchard, Rémi Lamontagne, Albert Bailey, Peter Bergman, Howard Ratner, Jack Tesfaye, Yoseph Saint-Martin, Monique Bacher, Yves Carrier, Louise Charbonneau, Roland Clarfield, A. Mark Collier, Brian Dastoor, Dolly Germain, Marcel Kissel, Catherine Krieger, Monique Kushnir, Seymour Masson, Hélène Morin, Jacques Nair, Vasavan Neirinck, Leonard Suissa, Samy |
| description | We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini—Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale—ll, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases.
Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P |
| doi_str_mv | 10.1056/NEJM199005033221804 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1983240815</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1983240815</sourcerecordid><originalsourceid>FETCH-LOGICAL-c382t-94f154d8d9d0a4bd5716025c2ae62747f0e1dd12040c6478ba3e1f968449ef6f3</originalsourceid><addsrcrecordid>eNp9kN1qGzEQhUVoSR0nTxAKCy3kImwz-tld6TK4SZri_ECc60VezdYyltaRZEJ61XfoG-ZJqmKTq1LdjJjzzRnmEHJM4QuFqj67vfh-Q5UCqIBzxqgEsUdGtOK8FALqd2QEwGQpGsU_kIMYl5AfFWqf7GeYZ4sRWc8wBb14MWHQzvpBd8Ea6_H11-8pdjYtrC8mg5tbr5MdfDELqJNDn4os3Ode_sbiOYPFtU8YHBqrE5YPSf_A4nz1c4HWYTiJxVcbUUc8JO97vYp4tKtj8nh5MZt8K6d3V9eT82nZcclSqURPK2GkUQa0mJuqoTWwqmMaa9aIpgekxlAGArpaNHKuOdJe1VIIhX3d8zH5tPVdh-FpgzG1y2ETfF7ZUiU5EyBzUmPCt1QXhhgD9u06WKfDS0uh_Rty-4-Q89THnfdmng9-m9mlmvXPO13HTq_6oH1n4xsmaqqE5Bk73WLOxdbj0v136R9q1pH5</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983240815</pqid></control><display><type>article</type><title>Tetrahydroaminoacridine–Lecithin Combination Treatment in Patients with Intermediate-Stage Alzheimer's Disease: Results of a Canadian Double-Blind, Crossover, Multicenter Study</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>New England Journal of Medicine</source><creator>Gauthier, Louise ; Gauthier, Serge ; Bouchard, Rémi ; Lamontagne, Albert ; Bailey, Peter ; Bergman, Howard ; Ratner, Jack ; Tesfaye, Yoseph ; Saint-Martin, Monique ; Bacher, Yves ; Carrier, Louise ; Charbonneau, Roland ; Clarfield, A. Mark ; Collier, Brian ; Dastoor, Dolly ; Germain, Marcel ; Kissel, Catherine ; Krieger, Monique ; Kushnir, Seymour ; Masson, Hélène ; Morin, Jacques ; Nair, Vasavan ; Neirinck, Leonard ; Suissa, Samy</creator><creatorcontrib>Gauthier, Louise ; Gauthier, Serge ; Bouchard, Rémi ; Lamontagne, Albert ; Bailey, Peter ; Bergman, Howard ; Ratner, Jack ; Tesfaye, Yoseph ; Saint-Martin, Monique ; Bacher, Yves ; Carrier, Louise ; Charbonneau, Roland ; Clarfield, A. Mark ; Collier, Brian ; Dastoor, Dolly ; Germain, Marcel ; Kissel, Catherine ; Krieger, Monique ; Kushnir, Seymour ; Masson, Hélène ; Morin, Jacques ; Nair, Vasavan ; Neirinck, Leonard ; Suissa, Samy</creatorcontrib><description>We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini—Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale—ll, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases.
Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P<0.05) after four weeks of treatment with THA.
Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis.
These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin. (N Engl J Med 1990; 322:1272–6.)
ALZHEIMER'S disease is a devastating and common neurologic disorder, and the search for symptomatic therapy has proceeded at an accelerated pace since the finding a decade ago of reduced cholinergic markers in the neocortex and hippocampus of patients.
1
Oral loading with acetylcholine precursors such as choline
2
or lecithin
3
has failed to help appreciably. Intracerebroventricular infusion of bethanechol, a direct muscarinic agonist, led to only modest increases in scores on the Mini—Mental State (MMS) test; in view of the surgical risks involved in implanting a pump and catheter, this treatment was abandoned.
4
Short-term acetylcholinesterase inhibitors such as physostigmine administered orally or . . .</description><identifier>ISSN: 0028-4793</identifier><identifier>EISSN: 1533-4406</identifier><identifier>DOI: 10.1056/NEJM199005033221804</identifier><identifier>PMID: 2183056</identifier><identifier>CODEN: NEJMAG</identifier><language>eng</language><publisher>Boston, MA: Massachusetts Medical Society</publisher><subject>Administration, Oral ; Aged ; Aged, 80 and over ; Alanine ; Alanine transaminase ; Alzheimer Disease - drug therapy ; Alzheimer's disease ; Aminoacridines - administration & dosage ; Biological and medical sciences ; Biopsy ; Cholinesterase Inhibitors - administration & dosage ; Cholinesterase Inhibitors - adverse effects ; Cholinesterase Inhibitors - therapeutic use ; Clinical trials ; Dementia ; Dementia disorders ; Double-Blind Method ; Drug dosages ; Drug Evaluation ; Drug Therapy, Combination ; Drug Tolerance ; Epidemiology ; Female ; Hepatocytes ; Hospitals ; Humans ; Intelligence Tests ; Lecithin ; Male ; Medical sciences ; Middle Aged ; Multicenter Studies as Topic ; Neurodegenerative diseases ; Neuropharmacology ; Patient Compliance ; Patients ; Pharmacology. Drug treatments ; Phosphatidylcholines - administration & dosage ; Phosphatidylcholines - adverse effects ; Phosphatidylcholines - therapeutic use ; Psychiatry ; Randomized Controlled Trials as Topic ; Tacrine - administration & dosage ; Tacrine - adverse effects ; Tacrine - therapeutic use ; Titration</subject><ispartof>The New England journal of medicine, 1990-05, Vol.322 (18), p.1272-1276</ispartof><rights>1993 INIST-CNRS</rights><rights>Copyright Massachusetts Medical Society May 3, 1990</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c382t-94f154d8d9d0a4bd5716025c2ae62747f0e1dd12040c6478ba3e1f968449ef6f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.nejm.org/doi/pdf/10.1056/NEJM199005033221804$$EPDF$$P50$$Gmms$$H</linktopdf><linktohtml>$$Uhttps://www.nejm.org/doi/full/10.1056/NEJM199005033221804$$EHTML$$P50$$Gmms$$H</linktohtml><link.rule.ids>314,776,780,2746,2747,26080,27901,27902,52357,54039</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4619483$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2183056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gauthier, Louise</creatorcontrib><creatorcontrib>Gauthier, Serge</creatorcontrib><creatorcontrib>Bouchard, Rémi</creatorcontrib><creatorcontrib>Lamontagne, Albert</creatorcontrib><creatorcontrib>Bailey, Peter</creatorcontrib><creatorcontrib>Bergman, Howard</creatorcontrib><creatorcontrib>Ratner, Jack</creatorcontrib><creatorcontrib>Tesfaye, Yoseph</creatorcontrib><creatorcontrib>Saint-Martin, Monique</creatorcontrib><creatorcontrib>Bacher, Yves</creatorcontrib><creatorcontrib>Carrier, Louise</creatorcontrib><creatorcontrib>Charbonneau, Roland</creatorcontrib><creatorcontrib>Clarfield, A. Mark</creatorcontrib><creatorcontrib>Collier, Brian</creatorcontrib><creatorcontrib>Dastoor, Dolly</creatorcontrib><creatorcontrib>Germain, Marcel</creatorcontrib><creatorcontrib>Kissel, Catherine</creatorcontrib><creatorcontrib>Krieger, Monique</creatorcontrib><creatorcontrib>Kushnir, Seymour</creatorcontrib><creatorcontrib>Masson, Hélène</creatorcontrib><creatorcontrib>Morin, Jacques</creatorcontrib><creatorcontrib>Nair, Vasavan</creatorcontrib><creatorcontrib>Neirinck, Leonard</creatorcontrib><creatorcontrib>Suissa, Samy</creatorcontrib><title>Tetrahydroaminoacridine–Lecithin Combination Treatment in Patients with Intermediate-Stage Alzheimer's Disease: Results of a Canadian Double-Blind, Crossover, Multicenter Study</title><title>The New England journal of medicine</title><addtitle>N Engl J Med</addtitle><description>We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini—Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale—ll, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases.
Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P<0.05) after four weeks of treatment with THA.
Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis.
These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin. (N Engl J Med 1990; 322:1272–6.)
ALZHEIMER'S disease is a devastating and common neurologic disorder, and the search for symptomatic therapy has proceeded at an accelerated pace since the finding a decade ago of reduced cholinergic markers in the neocortex and hippocampus of patients.
1
Oral loading with acetylcholine precursors such as choline
2
or lecithin
3
has failed to help appreciably. Intracerebroventricular infusion of bethanechol, a direct muscarinic agonist, led to only modest increases in scores on the Mini—Mental State (MMS) test; in view of the surgical risks involved in implanting a pump and catheter, this treatment was abandoned.
4
Short-term acetylcholinesterase inhibitors such as physostigmine administered orally or . . .</description><subject>Administration, Oral</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer's disease</subject><subject>Aminoacridines - administration & dosage</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cholinesterase Inhibitors - administration & dosage</subject><subject>Cholinesterase Inhibitors - adverse effects</subject><subject>Cholinesterase Inhibitors - therapeutic use</subject><subject>Clinical trials</subject><subject>Dementia</subject><subject>Dementia disorders</subject><subject>Double-Blind Method</subject><subject>Drug dosages</subject><subject>Drug Evaluation</subject><subject>Drug Therapy, Combination</subject><subject>Drug Tolerance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Hepatocytes</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Intelligence Tests</subject><subject>Lecithin</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multicenter Studies as Topic</subject><subject>Neurodegenerative diseases</subject><subject>Neuropharmacology</subject><subject>Patient Compliance</subject><subject>Patients</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphatidylcholines - administration & dosage</subject><subject>Phosphatidylcholines - adverse effects</subject><subject>Phosphatidylcholines - therapeutic use</subject><subject>Psychiatry</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Tacrine - administration & dosage</subject><subject>Tacrine - adverse effects</subject><subject>Tacrine - therapeutic use</subject><subject>Titration</subject><issn>0028-4793</issn><issn>1533-4406</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kN1qGzEQhUVoSR0nTxAKCy3kImwz-tld6TK4SZri_ECc60VezdYyltaRZEJ61XfoG-ZJqmKTq1LdjJjzzRnmEHJM4QuFqj67vfh-Q5UCqIBzxqgEsUdGtOK8FALqd2QEwGQpGsU_kIMYl5AfFWqf7GeYZ4sRWc8wBb14MWHQzvpBd8Ea6_H11-8pdjYtrC8mg5tbr5MdfDELqJNDn4os3Ode_sbiOYPFtU8YHBqrE5YPSf_A4nz1c4HWYTiJxVcbUUc8JO97vYp4tKtj8nh5MZt8K6d3V9eT82nZcclSqURPK2GkUQa0mJuqoTWwqmMaa9aIpgekxlAGArpaNHKuOdJe1VIIhX3d8zH5tPVdh-FpgzG1y2ETfF7ZUiU5EyBzUmPCt1QXhhgD9u06WKfDS0uh_Rty-4-Q89THnfdmng9-m9mlmvXPO13HTq_6oH1n4xsmaqqE5Bk73WLOxdbj0v136R9q1pH5</recordid><startdate>19900503</startdate><enddate>19900503</enddate><creator>Gauthier, Louise</creator><creator>Gauthier, Serge</creator><creator>Bouchard, Rémi</creator><creator>Lamontagne, Albert</creator><creator>Bailey, Peter</creator><creator>Bergman, Howard</creator><creator>Ratner, Jack</creator><creator>Tesfaye, Yoseph</creator><creator>Saint-Martin, Monique</creator><creator>Bacher, Yves</creator><creator>Carrier, Louise</creator><creator>Charbonneau, Roland</creator><creator>Clarfield, A. Mark</creator><creator>Collier, Brian</creator><creator>Dastoor, Dolly</creator><creator>Germain, Marcel</creator><creator>Kissel, Catherine</creator><creator>Krieger, Monique</creator><creator>Kushnir, Seymour</creator><creator>Masson, Hélène</creator><creator>Morin, Jacques</creator><creator>Nair, Vasavan</creator><creator>Neirinck, Leonard</creator><creator>Suissa, Samy</creator><general>Massachusetts Medical Society</general><scope>IQODW</scope><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>0TZ</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K0Y</scope><scope>LK8</scope><scope>M0R</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>19900503</creationdate><title>Tetrahydroaminoacridine–Lecithin Combination Treatment in Patients with Intermediate-Stage Alzheimer's Disease</title><author>Gauthier, Louise ; Gauthier, Serge ; Bouchard, Rémi ; Lamontagne, Albert ; Bailey, Peter ; Bergman, Howard ; Ratner, Jack ; Tesfaye, Yoseph ; Saint-Martin, Monique ; Bacher, Yves ; Carrier, Louise ; Charbonneau, Roland ; Clarfield, A. Mark ; Collier, Brian ; Dastoor, Dolly ; Germain, Marcel ; Kissel, Catherine ; Krieger, Monique ; Kushnir, Seymour ; Masson, Hélène ; Morin, Jacques ; Nair, Vasavan ; Neirinck, Leonard ; Suissa, Samy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-94f154d8d9d0a4bd5716025c2ae62747f0e1dd12040c6478ba3e1f968449ef6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Administration, Oral</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alanine</topic><topic>Alanine transaminase</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer's disease</topic><topic>Aminoacridines - administration & dosage</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Cholinesterase Inhibitors - administration & dosage</topic><topic>Cholinesterase Inhibitors - adverse effects</topic><topic>Cholinesterase Inhibitors - therapeutic use</topic><topic>Clinical trials</topic><topic>Dementia</topic><topic>Dementia disorders</topic><topic>Double-Blind Method</topic><topic>Drug dosages</topic><topic>Drug Evaluation</topic><topic>Drug Therapy, Combination</topic><topic>Drug Tolerance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Hepatocytes</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Intelligence Tests</topic><topic>Lecithin</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multicenter Studies as Topic</topic><topic>Neurodegenerative diseases</topic><topic>Neuropharmacology</topic><topic>Patient Compliance</topic><topic>Patients</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphatidylcholines - administration & dosage</topic><topic>Phosphatidylcholines - adverse effects</topic><topic>Phosphatidylcholines - therapeutic use</topic><topic>Psychiatry</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Tacrine - administration & dosage</topic><topic>Tacrine - adverse effects</topic><topic>Tacrine - therapeutic use</topic><topic>Titration</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gauthier, Louise</creatorcontrib><creatorcontrib>Gauthier, Serge</creatorcontrib><creatorcontrib>Bouchard, Rémi</creatorcontrib><creatorcontrib>Lamontagne, Albert</creatorcontrib><creatorcontrib>Bailey, Peter</creatorcontrib><creatorcontrib>Bergman, Howard</creatorcontrib><creatorcontrib>Ratner, Jack</creatorcontrib><creatorcontrib>Tesfaye, Yoseph</creatorcontrib><creatorcontrib>Saint-Martin, Monique</creatorcontrib><creatorcontrib>Bacher, Yves</creatorcontrib><creatorcontrib>Carrier, Louise</creatorcontrib><creatorcontrib>Charbonneau, Roland</creatorcontrib><creatorcontrib>Clarfield, A. Mark</creatorcontrib><creatorcontrib>Collier, Brian</creatorcontrib><creatorcontrib>Dastoor, Dolly</creatorcontrib><creatorcontrib>Germain, Marcel</creatorcontrib><creatorcontrib>Kissel, Catherine</creatorcontrib><creatorcontrib>Krieger, Monique</creatorcontrib><creatorcontrib>Kushnir, Seymour</creatorcontrib><creatorcontrib>Masson, Hélène</creatorcontrib><creatorcontrib>Morin, Jacques</creatorcontrib><creatorcontrib>Nair, Vasavan</creatorcontrib><creatorcontrib>Neirinck, Leonard</creatorcontrib><creatorcontrib>Suissa, Samy</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>New England Journal of Medicine</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><jtitle>The New England journal of medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gauthier, Louise</au><au>Gauthier, Serge</au><au>Bouchard, Rémi</au><au>Lamontagne, Albert</au><au>Bailey, Peter</au><au>Bergman, Howard</au><au>Ratner, Jack</au><au>Tesfaye, Yoseph</au><au>Saint-Martin, Monique</au><au>Bacher, Yves</au><au>Carrier, Louise</au><au>Charbonneau, Roland</au><au>Clarfield, A. Mark</au><au>Collier, Brian</au><au>Dastoor, Dolly</au><au>Germain, Marcel</au><au>Kissel, Catherine</au><au>Krieger, Monique</au><au>Kushnir, Seymour</au><au>Masson, Hélène</au><au>Morin, Jacques</au><au>Nair, Vasavan</au><au>Neirinck, Leonard</au><au>Suissa, Samy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tetrahydroaminoacridine–Lecithin Combination Treatment in Patients with Intermediate-Stage Alzheimer's Disease: Results of a Canadian Double-Blind, Crossover, Multicenter Study</atitle><jtitle>The New England journal of medicine</jtitle><addtitle>N Engl J Med</addtitle><date>1990-05-03</date><risdate>1990</risdate><volume>322</volume><issue>18</issue><spage>1272</spage><epage>1276</epage><pages>1272-1276</pages><issn>0028-4793</issn><eissn>1533-4406</eissn><coden>NEJMAG</coden><abstract>We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini—Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale—ll, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases.
Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P<0.05) after four weeks of treatment with THA.
Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis.
These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin. (N Engl J Med 1990; 322:1272–6.)
ALZHEIMER'S disease is a devastating and common neurologic disorder, and the search for symptomatic therapy has proceeded at an accelerated pace since the finding a decade ago of reduced cholinergic markers in the neocortex and hippocampus of patients.
1
Oral loading with acetylcholine precursors such as choline
2
or lecithin
3
has failed to help appreciably. Intracerebroventricular infusion of bethanechol, a direct muscarinic agonist, led to only modest increases in scores on the Mini—Mental State (MMS) test; in view of the surgical risks involved in implanting a pump and catheter, this treatment was abandoned.
4
Short-term acetylcholinesterase inhibitors such as physostigmine administered orally or . . .</abstract><cop>Boston, MA</cop><pub>Massachusetts Medical Society</pub><pmid>2183056</pmid><doi>10.1056/NEJM199005033221804</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-4793 |
| ispartof | The New England journal of medicine, 1990-05, Vol.322 (18), p.1272-1276 |
| issn | 0028-4793 1533-4406 |
| language | eng |
| recordid | cdi_proquest_journals_1983240815 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; New England Journal of Medicine |
| subjects | Administration, Oral Aged Aged, 80 and over Alanine Alanine transaminase Alzheimer Disease - drug therapy Alzheimer's disease Aminoacridines - administration & dosage Biological and medical sciences Biopsy Cholinesterase Inhibitors - administration & dosage Cholinesterase Inhibitors - adverse effects Cholinesterase Inhibitors - therapeutic use Clinical trials Dementia Dementia disorders Double-Blind Method Drug dosages Drug Evaluation Drug Therapy, Combination Drug Tolerance Epidemiology Female Hepatocytes Hospitals Humans Intelligence Tests Lecithin Male Medical sciences Middle Aged Multicenter Studies as Topic Neurodegenerative diseases Neuropharmacology Patient Compliance Patients Pharmacology. Drug treatments Phosphatidylcholines - administration & dosage Phosphatidylcholines - adverse effects Phosphatidylcholines - therapeutic use Psychiatry Randomized Controlled Trials as Topic Tacrine - administration & dosage Tacrine - adverse effects Tacrine - therapeutic use Titration |
| title | Tetrahydroaminoacridine–Lecithin Combination Treatment in Patients with Intermediate-Stage Alzheimer's Disease: Results of a Canadian Double-Blind, Crossover, Multicenter Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T11%3A09%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tetrahydroaminoacridine%E2%80%93Lecithin%20Combination%20Treatment%20in%20Patients%20with%20Intermediate-Stage%20Alzheimer's%20Disease:%20Results%20of%20a%20Canadian%20Double-Blind,%20Crossover,%20Multicenter%20Study&rft.jtitle=The%20New%20England%20journal%20of%20medicine&rft.au=Gauthier,%20Louise&rft.date=1990-05-03&rft.volume=322&rft.issue=18&rft.spage=1272&rft.epage=1276&rft.pages=1272-1276&rft.issn=0028-4793&rft.eissn=1533-4406&rft.coden=NEJMAG&rft_id=info:doi/10.1056/NEJM199005033221804&rft_dat=%3Cproquest_cross%3E1983240815%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1983240815&rft_id=info:pmid/2183056&rfr_iscdi=true |