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A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00710684
First Posted: July 4, 2008
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The study is designed to investigate the safety and efficacy of SB-742457 when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease.

Condition Intervention Phase
Alzheimer's Disease Drug: SB-742457 15mg Drug: SB-742457 35mg Drug: Placebo Drug: donepezil 5-10mg Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Study AZ3110866, a Fixed Dose Study of SB-742457 Versus Placebo When Added to Existing Donepezil Treatment in Subjects With Mild-to-moderate Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24 [ Time Frame: Baseline(Week 0) and Week 24 ]
    ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the case report form (CRF) for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean is presented.

  • Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24 [ Time Frame: Baseline(Week 0) and Week 24 ]
    The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.


Secondary Outcome Measures:
  • Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24 [ Time Frame: Baseline (Week 0) and Week 24 ]
    RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

  • Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48 [ Time Frame: Baseline (Week 0) and Week 12, 36 and 48 ]
    ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the CRF for questions 3 to 6 and 8 to 11. In cases where more than one question was missing, a total score was not be imputed. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been present

  • Change From Baseline in CDR-SB Score at Week 12, 36 and 48 [ Time Frame: Baseline (Week 0) and Week 12, 36, 48 ]
    The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

  • Change From Baseline in RBANS Score at Week 12, 36 and 48 [ Time Frame: Baseline (Week 0) and Week 12, 36 and 48 ]
    RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

  • Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48 [ Time Frame: Baseline (Week 0) and Week 12, 24, 36 and 48 ]
    The ADCS-ADL is an interviewer-administered informant-based scale where the informant (caregiver) responds to 23 activities of daily living questions about the participant. The questions ranged from basic to instrumental activities of daily living and take approximately 20 minutes to complete. The Total score ranges from 0-78 and a higher score signified greater functional ability. The questionnaire was split into two types of questions, an initial question relating to whether a participant had completed a particular activity and then a follow on question which scored how much assistance the participant had required if they had performed that particular activity. The total score was calculated by adding up the responses for each of the individual activities. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

  • Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48 [ Time Frame: Baseline (Week 0) and Week 24 and 48 ]
    The MMSE consisted of 11 items covering orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Scores for each of the 11 individual tests were not recorded on the CRF, therefore if any item was missing then the total score was be set to missing. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase [ Time Frame: Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal) ]
    An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

  • Number of Participants With Parameters of Clinical Concern - Hematology [ Time Frame: Up to Week 48 ]
    Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Eosinophils (high-2), Hematocrit (low- 0.8, high-1.2), Lymphocytes (low-0.75, high-1.5), Mean Corpuscle Hemoglobin (MCH) (low-0.8, high-1.2), Monocytes(low-0.75, high-2), Neutrophil bands (high-10), Platelet count (low-100, high-500), Segmented Neutrophils (low-0.75, high-1.3), Total Neutrophils (low-0.75, high-1.5), and white blood cells (WBC) (low-3, high-15).

  • Number of Participants With Parameters of Clinical Concern - Clinical Chemistry [ Time Frame: Up to Week 48 ]
    Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Alanine Amino Transferase (ALT) (high-1.5), Alkaline Phosphatase (high-1.5), Aspartate Amino Transferase (ASAT) (high-1.5), BUN/Creatinine ratio (high-1.5), Calcium (low- 0.75, high-1.25), Carbon dioxide content/Bicarbonate (low-15, high- 40), Cholesterol (high-1.25), Creatine Kinase ((low- 0.5, high-1.25), Creatinine (low- 0.5, high-1.25), Direct Bilirubin (high-1.5), Gamma Glutamyl Transferase (GGT) (high-2), Glucose (low- 3.6, high-7.8), HDL Cholesterol (low-0.65), LDL Cholesterol (hig-1.25), Magnesium (low-0.5, high-2), Phosphorus inorganic (low- 0.5, high-1.5), Potassium (low- 3, high-5.5), Sodium (low- 130, high-150), Total Bilirubin (high-1.5), Triglycerides (high -4) and Urea/BUN (high-11).

  • Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss) [ Time Frame: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 ]
    AUCτss of SB-742457 was estimated via nonlinear mixed effect analysis. This pharmacokinetic(PK) model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.

  • Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss) [ Time Frame: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 ]
    Cmin-ss was estimated via nonlinear mixed effect analysis. This PK model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.

  • Exposure Estimates for Donepezil (Cavgss) [ Time Frame: Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 ]
    Participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) were allowed to participate in this study. Cavgss for donepezil approximately 12 to 20 hours after dosing were summarized by donepezil dose level 5 mg/7.5 mg/10 mg/15 mg.

  • Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene [ Time Frame: Baseline (Week 0) to Week 24 and Week 48 ]
    Genetic analyses was conducted to assess the effect of APOE4 carriage. ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five-point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores were recorded on the CRF for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.

  • Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene [ Time Frame: Baseline (Week 0) to Week 24 and Week 48 ]
    Genetic analyses was conducted to assess the effect of APOE4 carriage. The CDR-SB is an interviewer administered scale and impairment is scored in following categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment was scored on a scale in which none =0, questionable =0.5, mild =1, moderate =2 and severe =3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher score indicating severe impairment. If there were any missing items then CDR-SB was set to missing and was not imputed. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.

  • Change From Baseline in RBANS Scale in Participants With APOE4 Gene [ Time Frame: Baseline (Week 0) to Week 24 and Week 48 ]
    Genetic analyses was conducted to assess the effect of APOE4 carriage. RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.


Enrollment: 682
Actual Study Start Date: July 1, 2008
Study Completion Date: November 16, 2010
Primary Completion Date: May 21, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DONEPEZIL + SB-742457 15 MG
SB-742457 - 15mg added to existing donepezil treatment
Drug: SB-742457 15mg
SB-742457 - 15mg added to existing donepezil treatment
Drug: donepezil 5-10mg
existing donepezil treatment
Placebo Comparator: DONEPEZIL + PLACEBO
Placebo added to existing donepezil
Drug: Placebo
Placebo added to existing donepezil
Drug: donepezil 5-10mg
existing donepezil treatment
Experimental: DONEPEZIL + SB-742457 35 MG
SB-742457 - 35mg added to existing donepezil
Drug: SB-742457 35mg
SB-742457 - 35mg added to existing donepezil
Drug: donepezil 5-10mg
existing donepezil treatment

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects and their caregivers must provide informed consent prior to study entry.
  • Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with no evidence of disorders that are thought to be the cause of, or contributing to the severity of the subject's dementia and a documented history of at least 6 months of ongoing donepezil therapy with stable dosing for at least the last 2 months.
  • Subjects must have a regular caregiver who is willing to attend visits, oversee the subject's compliance with the study and report on the subject's status.
  • Female subjects of child-bearing potential must agree to abstinence or an approved form of birth control.
  • Subjects must have adequate blood pressure and laboratory values.

Exclusion Criteria:

  • Subjects with a diagnosis of possible, probable or definite vascular dementia may not participate.
  • Subjects with known hypersensitivity to sunlight or a history of seizures, previous exposure to SB-742457, taking agents for which there is a theoretical risk of interaction with SB-742457, or taking medication for Alzheimer's disease or centrally acting agents which might impact study outcomes may not participate.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00710684


  Hide Study Locations
Locations
United States, Arizona
GSK Investigational Site
Litchfield Park, Arizona, United States, 85340
United States, California
GSK Investigational Site
Fresno, California, United States, 93720
GSK Investigational Site
Rancho Mirage, California, United States, 92270
GSK Investigational Site
San Francisco, California, United States, 94109
United States, Florida
GSK Investigational Site
Hallandale Beach, Florida, United States, 33009
GSK Investigational Site
Hialeah, Florida, United States, 33016
United States, New Jersey
GSK Investigational Site
Manchester, New Jersey, United States, 08759
United States, New York
GSK Investigational Site
Syracuse, New York, United States, 13210
United States, North Carolina
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210
United States, Oklahoma
GSK Investigational Site
Tulsa, Oklahoma, United States, 74104
United States, Tennessee
GSK Investigational Site
Memphis, Tennessee, United States, 38119
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78757
United States, Vermont
GSK Investigational Site
Bennington, Vermont, United States, 05201
Argentina
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1022AAO
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1405BCH
GSK Investigational Site
Ciudad de Buenos Aires, Buenos Aires, Argentina, C1431FWO
GSK Investigational Site
La Plata, Buenos Aires, Argentina, B1900AVG
GSK Investigational Site
Cordoba, Córdova, Argentina, 5000
GSK Investigational Site
Buenos Aires, Argentina, 1425
GSK Investigational Site
Santa Fe, Argentina, 3000
Australia, New South Wales
GSK Investigational Site
Kogarah, New South Wales, Australia, 2217
Australia, Queensland
GSK Investigational Site
Herston, Queensland, Australia, 4029
Australia, South Australia
GSK Investigational Site
Woodville, South Australia, Australia, 5011
Australia, Victoria
GSK Investigational Site
Ballarat, Victoria, Australia, 3350
GSK Investigational Site
Heidelberg West, Victoria, Australia, 3084
GSK Investigational Site
Kew, Victoria, Australia, 3101
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Canada, New Brunswick
GSK Investigational Site
Saint John, New Brunswick, Canada, E2L 3L6
Canada, Nova Scotia
GSK Investigational Site
Kentville, Nova Scotia, Canada, B4N 4K9
Canada, Ontario
GSK Investigational Site
Ottawa, Ontario, Canada, K1G 4G3
GSK Investigational Site
Peterborough, Ontario, Canada, K9H 2P4
GSK Investigational Site
Toronto, Ontario, Canada, M3B 2S7
GSK Investigational Site
Toronto, Ontario, Canada, M6M 3Z5
Canada, Quebec
GSK Investigational Site
Greenfield Park, Quebec, Canada, J4V 2J2
GSK Investigational Site
Montreal, Quebec, Canada, H1T 2M4
GSK Investigational Site
Sherbrooke, Quebec, Canada, J1H 1Z1
GSK Investigational Site
Sherbrooke, Quebec, Canada, J1J 3H5
Canada
GSK Investigational Site
Québec, Canada, G1R 3X5
Chile
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7510186
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7560356
GSK Investigational Site
Viña del Mar, Valparaíso, Chile, 252-0997
GSK Investigational Site
Santiago, Chile
Czechia
GSK Investigational Site
Melnik, Czechia, 27601
GSK Investigational Site
Olomouc, Czechia, 775 20
GSK Investigational Site
Ostrava, Czechia, 702 00
GSK Investigational Site
Pardubice, Czechia, 53203
GSK Investigational Site
Plzen, Czechia, 301 00
GSK Investigational Site
Praha 10, Czechia, 10000
GSK Investigational Site
Praha 1, Czechia, 110 00
GSK Investigational Site
Praha 4, Czechia, 14059
Germany
GSK Investigational Site
Ellwangen, Baden-Wuerttemberg, Germany, 73479
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70176
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89075
GSK Investigational Site
Alzenau, Bayern, Germany, 63755
GSK Investigational Site
Guenzburg, Bayern, Germany, 89312
GSK Investigational Site
Muenchen, Bayern, Germany, 81675
GSK Investigational Site
Regensburg, Bayern, Germany, 93053
GSK Investigational Site
Unterhaching, Bayern, Germany, 82008
GSK Investigational Site
Bad Homburg, Hessen, Germany, 61348
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19053
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
GSK Investigational Site
Achim, Niedersachsen, Germany, 28832
GSK Investigational Site
Aachen, Nordrhein-Westfalen, Germany, 52062
GSK Investigational Site
Bad Honnef, Nordrhein-Westfalen, Germany, 53604
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44869
GSK Investigational Site
Dresden, Sachsen, Germany, 01097
GSK Investigational Site
Dresden, Sachsen, Germany, 01309
GSK Investigational Site
Jena, Thueringen, Germany, 07743
GSK Investigational Site
Berlin, Germany, 10961
GSK Investigational Site
Berlin, Germany, 12163
GSK Investigational Site
Berlin, Germany, 13439
Italy
GSK Investigational Site
Chieti Scalo, Abruzzo, Italy, 66013
GSK Investigational Site
Napoli, Campania, Italy, 80131
GSK Investigational Site
San Felice A Cancello - Caserta, Campania, Italy, 81027
GSK Investigational Site
Cassino (FR), Lazio, Italy, 03043
GSK Investigational Site
Roma, Lazio, Italy, 00148
GSK Investigational Site
Roma, Lazio, Italy, 00163
GSK Investigational Site
Brescia, Lombardia, Italy, 25125
GSK Investigational Site
Castellanza (VA), Lombardia, Italy, 21053
GSK Investigational Site
Milano, Lombardia, Italy, 20122
GSK Investigational Site
Milano, Lombardia, Italy, 20132
GSK Investigational Site
Rho, Lombardia, Italy, 20017
GSK Investigational Site
Torino, Piemonte, Italy, 10126
GSK Investigational Site
Lido Di Camaiore (LU), Toscana, Italy, 55043
GSK Investigational Site
Pisa, Toscana, Italy, 56126
GSK Investigational Site
Perugia, Umbria, Italy, 06156
GSK Investigational Site
Valdagno (VI), Veneto, Italy, 36078
GSK Investigational Site
Verona, Veneto, Italy, 37126
Spain
GSK Investigational Site
Baracaldo/Vizcaya, Spain, 48903
GSK Investigational Site
Barcelona, Spain, 08003
GSK Investigational Site
Barcelona, Spain, 08014
GSK Investigational Site
Barcelona, Spain, 08907
GSK Investigational Site
Burgos, Spain, 09006
GSK Investigational Site
Castellón, Spain, 12004
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Murcia, Spain, 30120
GSK Investigational Site
Salamanca, Spain, 37007
GSK Investigational Site
San Sebastián, Spain, 20014
GSK Investigational Site
San Vicente Del Raspeig/Alicante, Spain, 03690
GSK Investigational Site
Valencia, Spain, 46010
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00710684     History of Changes
Other Study ID Numbers: AZ3110866
First Submitted: June 30, 2008
First Posted: July 4, 2008
Results First Submitted: August 18, 2017
Results First Posted: December 7, 2017
Last Update Posted: December 7, 2017
Last Verified: November 2017

Keywords provided by GlaxoSmithKline:
Alzheimer's disease cognition SB-742457

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents