Abstract

Blood levels of homocysteine are elevated in Alzheimer's disease (AD), and hyperhomocysteinemia may contributed to disease pathophysiology by vascular and direct neurotoxic mechanisms. Homocysteine levels can be reduced to administrating of high dose supplements of folate, vitamin B6 and vitamin B12. We propose a multicenter, randomized, controlled clinical trial to determine whether reduction of homocysteine levels with high-dose folate/B6/B12 supplementation will slow the rate of cognitive decline in subjects with AD. This will be a parallel design study, including two groups of unequal size: (60% of subjects will receive daily high dose supplements (folate 5mg, vitamin B6 50MG, vitamin B12 1 mg), and 40% will receive identically appearing placebo; the duration of treatment will be 18 months. The primary outcome measure will be longitudinal decline in the ADAScog. To power the trial to detect a 25% reduction in rate of ADAScog decline (80% power, alpha=0.05, drop-out estimate 20%, drop-in estimate 10%), we will enroll a total of 400 subjects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AG010483-12S1
Application #
6655732
Study Section
Special Emphasis Panel (ZAG1)
Project Start
2002-09-15
Project End
2003-06-30
Budget Start
Budget End
Support Year
12
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Rockenstein, Edward; Ostroff, Gary; Dikengil, Fusun et al. (2018) Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies. J Neurosci 38:1000-1014
Edmonds, Emily C; Ard, M Colin; Edland, Steven D et al. (2018) Unmasking the benefits of donepezil via psychometrically precise identification of mild cognitive impairment: A secondary analysis of the ADCS vitamin E and donepezil in MCI study. Alzheimers Dement (N Y) 4:11-18
Chen, Yun-Fei; Ni, Xiao; Fleisher, Adam S et al. (2018) A simulation study comparing slope model with mixed-model repeated measure to assess cognitive data in clinical trials of Alzheimer's disease. Alzheimers Dement (N Y) 4:46-53
Jacobs, Diane M; Ard, M Colin; Salmon, David P et al. (2017) Potential implications of practice effects in Alzheimer's disease prevention trials. Alzheimers Dement (N Y) 3:531-535
Moussa, Charbel; Hebron, Michaeline; Huang, Xu et al. (2017) Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. J Neuroinflammation 14:1
Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384
El-Agnaf, Omar; Overk, Cassia; Rockenstein, Edward et al. (2017) Differential effects of immunotherapy with antibodies targeting ?-synuclein oligomers and fibrils in a transgenic model of synucleinopathy. Neurobiol Dis 104:85-96
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738
Tarrant, Sarah D; Bardach, Shoshana H; Bates, Kendra et al. (2017) The Effectiveness of Small-group Community-based Information Sessions on Clinical Trial Recruitment for Secondary Prevention of Alzheimer's Disease. Alzheimer Dis Assoc Disord 31:141-145
Kennedy, Richard E; Cutter, Gary R; Wang, Guoqiao et al. (2017) Challenging Assumptions About African American Participation in Alzheimer Disease Trials. Am J Geriatr Psychiatry 25:1150-1159

Showing the most recent 10 out of 294 publications