title: A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease.
abstract: OBJECTIVE
  A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes).
  
  
  METHODS
  Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52.
  
  
  RESULTS
  Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo.
  
  
  CONCLUSIONS
  Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood-brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment.
  
  
  METHODS
  This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated.
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC. rst36@georgetown.edu.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Turner
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Jacobo
authors.initials: J
authors.lastname: Mintzer
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Brigid A
authors.initials: BA
authors.lastname: Reynolds
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: James B
authors.initials: JB
authors.lastname: Brewer
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rissman
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Rema
authors.initials: R
authors.lastname: Raman
authors.affiliation: From the Department of Neurology (R.S.T., B.A.R.), Georgetown University, Washington, DC; the Department of Neurosciences (R.G.T., J.B.B., R.A.R., R.R., P.S.A.), University of California, San Diego, La Jolla; the Department of Internal Medicine (S.C.), Wake Forest University, Winston-Salem, NC; the Departments of Psychiatry, Neurology, and Neurobiology (C.H.v.D.), Yale University, New Haven, CT; and the Clinical Biotechnology Research Institute (J.M.), Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077185:Resveratrol; D013267:Stilbenes / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D013267:Stilbenes; D000077185:Resveratrol