A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease
- Registration Number
- NCT01224106
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This multi-center, randomized, double-blind, placebo-controlled parallel-group study will evaluate the effect of gantenerumab (RO4909832) on cognition and functioning and the safety and pharmacokinetics in participants with prodromal Alzheimer's Disease. Participants will be randomized to receive subcutaneous (SC) injections of either gantenerumab or placebo. Participants who consent to be part of the sub study will undergo positron emission tomography (PET) scanning to assess brain amyloid. The anticipated time on study treatment is 104 weeks in Part 1, with an option for an additional up to 2 years of treatment in Part 2, followed by an open-label extension (Part 3) until July 2020.
The dosing for Parts 1 and 2 was stopped after a planned futility interim analysis showed a low probability of meeting the primary outcome measure with the doses studied. The study has converted to open-label to investigate higher gantenerumab doses.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 799
- Adult participants, 50-85 years of age
- Participants with prodromal Alzheimer's disease who are not receiving memantine or cholinesterase inhibitors
- Has a study partner who in the investigator's judgement has frequent and sufficient contact with the participant as to be able to provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at clinic visits which require partner input for scale completion
- Has had sufficient education or work experience to exclude mental retardation
- Study partner has noticed a recent gradual decrease in participant's memory (over the last 12 months), which the participant may or may not be aware of
- Screening Mini Mental State Exam (MMSE) score of 24 or above
Additional inclusion criteria for sub study:
- Able and willing to travel to PET imaging center and complete the planned scanning sessions
- Past and planned exposure to ionizing radiation not exceeding safe and permissible levels
- Other prior or current neurologic or medical disorder which may currently or during the course of the study impair cognition or psychiatric functioning
- A history of stroke
- A documented history of transient ischemic attack within the last 12 months
- History of schizophrenia, schizoaffective or bipolar disorder
- Currently meets criteria for major depression
- Within the last 2 years, unstable or clinical significant cardiovascular disease (myocardial infarction, angina pectoris)
Additional exclusion criteria for sub study:
- Inclusion in a research and/or medical protocol involving PET ligands or other radioactive agents within 12 months
- Present or planned participation in a research and/or medical protocol involving PET ligands or radioactive agents other than study WN25203
- Have planned or are planning to have exposure to ionizing radiation that in combination with the planned administration with study amyloid PET ligand would result in a cumulative exposure that exceeds local recommended exposure limits
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo (Parts 1 and 2) Placebo Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Gantenerumab 225 mg (Parts 1 and 2) Gantenerumab Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Placebo (Parts 1 and 2) switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years. Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) Baseline up until a maximum of 5 years An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase) Baseline, Week 156 The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. The score range for ADAS-Cog-13 is from 0 to 85 with higher scores representing severe dysfunction.
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (\*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words\*4. The minimum score is 0 (worse).
Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 CSF biomarker phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD.
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) Baseline, Week 156 The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference.
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase) Baseline, Week 156 The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase) Baseline, Week 156 Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 The Cambridge Neuropsychological Test Automated Battery (CANTAB) ® is a cognitive test battery that incorporates a variety of executive and memory tasks in order to assess neuropsychological function. The end outcome as reported below, is a Z-Composite Score. The score range of the Z-Composite Score is from (-) infinity to (+) infinity with a score of zero representing the population mean, lower (negative) scores representing poorer cognitive outcomes and higher (positive) scores representing better cognitive outcomes.
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging.
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101 The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) Baseline up until a maximum of 4.5 years Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Gantenerumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Time to Onset of Dementia at Week 156 (OLE Phase) Baseline, Week 156 Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase) Baseline, Week 156 The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) Baseline up until a maximum of 5 years Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) Baseline, Week 104 The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101 The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) Baseline up until a maximum of 4.5 years An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase) Baseline, Week 156 The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase) Baseline, Week 156 FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (\*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words\*4. The minimum score is 0 (worse).
Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) Baseline, Week 152 Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging.
Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase) Baseline, Week 156 The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) Baseline, Week 156 The regions of the brain that were analyzed included cerebellum gray and composite reference.
Trial Locations
- Locations (139)
Butler Hospital
🇺🇸Providence, Rhode Island, United States
Hospital Mae de Deus
🇧🇷Porto Alegre, RS, Brazil
Rigshospitalet, Hukommelsesklinikken
🇩🇰Koebenhavn Oe, Denmark
Senior Adults Specialty Research
🇺🇸Austin, Texas, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
CEMIC
🇦🇷Buenos Aires, Argentina
Compass Research
🇺🇸The Villages, Florida, United States
Nathan Kline Institute
🇺🇸Orangeburg, New York, United States
University of Rochester Medical Center; Monroe Community Hospital
🇺🇸Rochester, New York, United States
St. Anne´s University Hospital; Clinical Trials Department
🇨🇿Brno, Czechia
Hopital Avicenne; Neurologie
🇫🇷Bobigny, France
CHU De Caen; Service De Neurologie Dejerine
🇫🇷Caen, France
IME - Instituto Médico Especializado; Ensayos Clínicos
🇦🇷Buenos Aires, Argentina
Especialidades Medicas LYS
🇨🇱Santiago, Chile
Kawartha Centre - Redefining Healthy Aging
🇨🇦Peterborough, Ontario, Canada
Hopital Hautepierre; Centre dInvestigation Clinique
🇫🇷Strasbourg, France
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, RS, Brazil
Hospital das Clinicas - FMUSP; Psiquiatria
🇧🇷Sao Paulo, SP, Brazil
Hospital das Clinicas - UFPR; Ciencias da Saude
🇧🇷Curitiba, PR, Brazil
NeuroSearch Developpements inc
🇨🇦Greenfield Park, Quebec, Canada
Zentralinstitut für Seelische Gesundheit Abt.Gerontopsychiatrie
🇩🇪Mannheim, Germany
Office of Dr Klaus Steinwachs Neurology & Psychiatry
🇩🇪Nürnberg, Germany
Ch Pitie Salpetriere; Cmrr Ile De France Salpetriere
🇫🇷Paris, France
Vestra Clinics s.r.o.
🇨🇿Rychnov nad Kneznou, Czechia
Universitätsklinikum Rostock Zentrum für Nervenheilkunde
🇩🇪Rostock, Germany
Hopital Pellegrin; Cmrr Aquitaine
🇫🇷Bordeaux, France
Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie
🇫🇷Bron, France
Universidade Federal de Sao Paulo - UNIFESPX; Neurologia
🇧🇷São Paulo, SP, Brazil
CHU de Rouen Hopital; Service de Neurologie
🇫🇷Rouen, France
Hospital Universitario de Saltillo
🇲🇽Saltillo, Mexico
PANAKEIA - Arzneimittelforschung Leipzig GmbH
🇩🇪Leipzig, Germany
Pharmakologisches Studienzentrum
🇩🇪Mittweida, Germany
Asan Medical Center.
🇰🇷Seoul, Korea, Republic of
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona
🇮🇹Torrette - Ancona, Marche, Italy
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Universitätsklinikum Ulm; Klinik für Neurologie
🇩🇪Ulm, Germany
Sverdlovsk Regional Clinical Psychoneurological War Veteran Hospital
🇷🇺Ekaterinburg, Russian Federation
Moorgreen Hospital; Memory Assessment & Rsch Ctr
🇬🇧Southampton, United Kingdom
Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC
🇲🇽Culiacan, Mexico
PALLMED Sp. z o.o. prowadząca NZOZ DOM SUE RYDER
🇵🇱Bydgoszcz, Poland
Hospital Universitario Dr. Peset; Servicio de Neurologia
🇪🇸Valencia, Spain
Hospital Universitario 12 de Octubre; Servicio de Neurologia
🇪🇸Madrid, Spain
Hospital Clinic i Provincial; Servicio de Neurologia
🇪🇸Barcelona, Spain
Charing Cross Hospital; Dept of Neurosciences
🇬🇧London, United Kingdom
Hospital Ramon y Cajal; Servicio de Neurologia
🇪🇸Madrid, Spain
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Campus for Ageing & Vitality; Clincal Ageing Research Unit
🇬🇧Newcastle, United Kingdom
Hospital Italiano
🇦🇷Buenos Aires, Argentina
ALPI-Inst. de Rehabilitacion Marcelo Fitte
🇦🇷Buenos Aires, Argentina
Mulieris
🇦🇷Caba, Argentina
Instituto De Neurología Cognitiva - INECO
🇦🇷Caba, Argentina
FLENI
🇦🇷Caba, Argentina
Instituto Kremer
🇦🇷Córdoba, Argentina
CENPIA; Neurología - Psicología
🇦🇷La Plata, Argentina
True North Clinical Research
🇨🇦New Minas, Nova Scotia, Canada
CRST Oy
🇫🇮Turku, Finland
Centro Medico San Francisco; Geriatrics
🇲🇽Monterrey, Mexico
Przychodnia Specjalistyczna PROSEN
🇵🇱Warszawa, Poland
mMED Maciej Czarnecki
🇵🇱Warszawa, Poland
Australian Alzheimer's Research Foundation
🇦🇺Nedlands, Western Australia, Australia
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
Infinity Clinical Research
🇺🇸Hollywood, Florida, United States
Roskamp Institute, Inc.
🇺🇸Sarasota, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Neurological Research Center
🇺🇸Hattiesburg, Mississippi, United States
Princeton Medical Institute
🇺🇸Princeton, New Jersey, United States
Texas Neurology PA
🇺🇸Dallas, Texas, United States
Royal Adelaide Hospital; Memory Trials Centre
🇦🇺Adelaide, South Australia, Australia
Centre for Memory and Aging
🇨🇦Toronto, Ontario, Canada
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
Oregon Health and Science University, Layton Aging and Alzheimer's Disease Center
🇺🇸Portland, Oregon, United States
Akdeniz University School of Medicine, Neurology Department
🇹🇷Antalya, Turkey
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research
🇺🇸Kalamazoo, Michigan, United States
Northeastern Pennsylvania Memory
🇺🇸Plains, Pennsylvania, United States
CHAUQ - Hôpital Enfant-Jésus
🇨🇦Quebec City, Quebec, Canada
Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
🇩🇰Aarhus N, Denmark
Hopital B Roger Salengro; Cmrr Lille
🇫🇷Lille, France
Hop Guillaume Et Rene Laennec; Cmrr St Herblain
🇫🇷St Herblain, France
Hopital de La Grave
🇫🇷Toulouse, France
Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin
🇩🇪Bonn, Germany
Univ Berlin; Klin fur Psychi & Psycho Charite
🇩🇪Berlin, Germany
Neurologische Praxis Dr. Andrej Pauls
🇩🇪München, Germany
Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
🇩🇪München, Germany
Universita' Di Parma Istituto Neurologia
🇮🇹Parma, Emilia-Romagna, Italy
Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica - Dipartimento di Neuroscienze
🇮🇹Modena, Emilia-Romagna, Italy
Azienda Ospedaliera Spedali Civili; Scienze Neurologiche
🇮🇹Brescia, Lombardia, Italy
IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer
🇮🇹Brescia, Lombardia, Italy
Irccs Multimedica Santa Maria; Unita' Di Neurologia
🇮🇹Castellanza, Lombardia, Italy
Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
🇮🇹Milano, Lombardia, Italy
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Uni Di Firenze Dip. Scienze Neurol Psic Sod Neurologia 1
🇮🇹Firenze, Toscana, Italy
Seoul National University Bundang Hospital; Neurology Department
🇰🇷Gyeonggi-do, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Mexico Americano
🇲🇽Guadalajara, Mexico CITY (federal District), Mexico
Hospital Universitario; Dr. Jose E. Gonzalez
🇲🇽Monterrey, Nuevo LEON, Mexico
Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
🇲🇽Guadalajara, Mexico
Jeroen Bosch Ziekenhuis; Polikliniek Geriatrie
🇳🇱'S Hertogenbosch, Netherlands
Brain Research Center B.V
🇳🇱Amsterdam, Netherlands
Podlaskie Centrum Psychogeriatrii
🇵🇱Białystok, Poland
NEURO - KARD Ośrodek Badań Klinicznych
🇵🇱Poznań, Poland
Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
🇵🇹Amadora, Portugal
Hospital de Santa Maria; Servico de Neurologia
🇵🇹Lisboa, Portugal
State autonomous institution of healthcare Inter-regional clinical and diagnostic center
🇷🇺Kazan, Russian Federation
City Clinical Hospital # 2 n.a. V.I. Razumovsky
🇷🇺Saratov, Russian Federation
Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department
🇷🇺St. Petersburg, Russian Federation
Hospital del Mar; Servicio de Neurologia
🇪🇸Barcelona, Spain
Hospital de Cruces; Servicio de Neurologia
🇪🇸Barakaldo, Vizcaya, Spain
Llandough Hospital; Llandough Hospital Memory Team 3rd Floor Academic Building
🇬🇧Cardiff, United Kingdom
Glasgow Memory Clinic
🇬🇧Glasgow, United Kingdom
Victoria Centre; Kingshill Research Centre
🇬🇧Swindon, United Kingdom
Hollins Park Hospital
🇬🇧Warrington, United Kingdom
Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
🇪🇸Barcelona, Spain
Hospital Universitario La Paz; Servicio de Neurologia
🇪🇸Madrid, Spain
Skånes Universitetssjukhus Malmö, Minneskliniken
🇸🇪Malmö, Sweden
Felix Platter-Spital Medizin Geriatrie
🇨🇭Basel, Switzerland
Istanbul University Istanbul School of Medicine; Neurology
🇹🇷Istanbul, Turkey
Ondokuz Mayis University School of Medicine; Neurology
🇹🇷Samsun, Turkey
St Margaret's Hospital
🇬🇧Epping, United Kingdom
Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik
🇩🇪Frankfurt, Germany
The Queen Elizabeth Hospital; Neurology
🇦🇺Woodville, South Australia, Australia
Prince of Wales Hospital, Academic Department for Old Age Psychiatry
🇦🇺Randwick, New South Wales, Australia
Yale University ADRU
🇺🇸New Haven, Connecticut, United States
Accelerated Enrollment Solutions
🇺🇸Orlando, Florida, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
McGill University; Sir Mortimer B Davis Jewish General Hospital; Neurological and Psychiatric
🇨🇦Montreal, Quebec, Canada
Biomedica Research Group
🇨🇱Santiago, Chile
Estimulacion Magnetica Trnscraneal de Mexico SC.
🇲🇽Mexico City, Mexico
Clinical Neuroscience Research Associates, Inc.
🇺🇸Bennington, Vermont, United States
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
🇦🇺Heidelberg West, Victoria, Australia
Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center
🇷🇺Saint Petersburg, Russian Federation
Fundació ACE
🇪🇸BArcelon, Barcelona, Spain
HUG; Département de santé mentale et de psychiatrie Unité de psychiatrie gériatrique
🇨🇭Chêne-Bourg, Switzerland
Alzheimer's Memory Center
🇺🇸Matthews, North Carolina, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care
🇦🇺Hornsby, New South Wales, Australia
Hospital Mutua De Terrasa; Servicio de Neurologia
🇪🇸Terrassa, Barcelona, Spain