Volunteers aged 75 years or older were recruited from September 2000 to June 2002 using voter registration and other purchased mailing lists from 4 US communities with academic medical centers: Hagerstown, Maryland (Johns Hopkins); Pittsburgh, Pennsylvania (University of Pittsburgh); Sacramento, California (University of California–Davis); and Winston-Salem and Greensboro, North Carolina (Wake Forest University). All participants were required to identify a proxy willing to be interviewed every 6 months at the time of each study visit. Signed informed consent was obtained from participants and their respective proxies.
Individuals with prevalent dementia (meeting Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] [DSM-IV] criteria for dementia18 or a score >0.5 on the Clinical Dementia Rating scale19 (link) [CDR]) were excluded from participation. Also excluded were individuals meeting any of the following criteria: (1) currently taking the anticoagulant warfarin; (2) taking cholinesterase inhibitors for cognitive problems or dementia (memantine had not been approved for use in the United States when the study began); (3) unwilling to discontinue taking over-the-counter G biloba for the duration of the study; (4) currently being treated with tricyclic antidepressants, antipsychotics, or other medications with significant psychotropic or central cholinergic effects (the anticholinergic effects of selective serotonin reuptake inhibitors were not believed to be substantial enough to warrant exclusion); (5) daily use of more than 400-IU vitamin E or unwillingness to reduce intake to this level; (6) history of bleeding disorders; (7) hospitalization for depression within the last year or electroconvulsive therapy within last 10 years; (8) history of Parkinson disease or taking anti-Parkinson medications; (9) abnormal thyroid tests, serum creatinine level greater than 2.0 mg/dL (to convert to μmol/L, multiply by 88.4), or liver function tests more than 2 times the upper limit of normal at baseline; (10) baseline vitamin B12 levels 210 pg/mL or lower (to convert to pmol/L, multiply by 0.7378); (11) hematocrit level less than 30%; (12) platelet count lower than 100 ×103/μL; (13) disease-related life expectancy of less than 5 years; or (14) known allergy to G biloba.
The recruitment procedures for the GEM Study have been described elsewhere.17 (link) Participants with mild cognitive impairment (MCI) were not excluded. The criteria for classification of MCI at baseline in the GEM Study were based on guidelines set forth by the International Working Group on Mild Cognitive Impairment.20 ,21 (link) In brief, individuals defined as having baseline MCI met both of the following 2 criteria: (1) impaired at or below the 10th percentile of Cardiovascular Health Study normative data, stratified by age and education, on at least 2 of 10 selected neuropsychological test scores from each cognitive domain, including memory, language, visuospatial abilities, attention, and executive function; and (2) CDR global score of 0.5.
Individuals with prevalent dementia (meeting Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] [DSM-IV] criteria for dementia18 or a score >0.5 on the Clinical Dementia Rating scale19 (link) [CDR]) were excluded from participation. Also excluded were individuals meeting any of the following criteria: (1) currently taking the anticoagulant warfarin; (2) taking cholinesterase inhibitors for cognitive problems or dementia (memantine had not been approved for use in the United States when the study began); (3) unwilling to discontinue taking over-the-counter G biloba for the duration of the study; (4) currently being treated with tricyclic antidepressants, antipsychotics, or other medications with significant psychotropic or central cholinergic effects (the anticholinergic effects of selective serotonin reuptake inhibitors were not believed to be substantial enough to warrant exclusion); (5) daily use of more than 400-IU vitamin E or unwillingness to reduce intake to this level; (6) history of bleeding disorders; (7) hospitalization for depression within the last year or electroconvulsive therapy within last 10 years; (8) history of Parkinson disease or taking anti-Parkinson medications; (9) abnormal thyroid tests, serum creatinine level greater than 2.0 mg/dL (to convert to μmol/L, multiply by 88.4), or liver function tests more than 2 times the upper limit of normal at baseline; (10) baseline vitamin B12 levels 210 pg/mL or lower (to convert to pmol/L, multiply by 0.7378); (11) hematocrit level less than 30%; (12) platelet count lower than 100 ×103/μL; (13) disease-related life expectancy of less than 5 years; or (14) known allergy to G biloba.
The recruitment procedures for the GEM Study have been described elsewhere.17 (link) Participants with mild cognitive impairment (MCI) were not excluded. The criteria for classification of MCI at baseline in the GEM Study were based on guidelines set forth by the International Working Group on Mild Cognitive Impairment.20 ,21 (link) In brief, individuals defined as having baseline MCI met both of the following 2 criteria: (1) impaired at or below the 10th percentile of Cardiovascular Health Study normative data, stratified by age and education, on at least 2 of 10 selected neuropsychological test scores from each cognitive domain, including memory, language, visuospatial abilities, attention, and executive function; and (2) CDR global score of 0.5.
