Evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer's disease suggests that anti-inflammatory medications may slow the rate of cognitive deterioration. We have selected two anti- inflammatory drugs for a therapeutic trial: hydroxychloroquine, an antimalarial agent with anti-inflammatory and immunomodulating effects useful in the treatment of rheumatic disease, and colchicine, an anti- inflammatory drug with anti-amyloidogenic activity. The trial employs a double-blind parallel design with three groups: hydroxychloroquine (200mg twice daily), colchicine (0.6mg twice daily) and placebo. A total of three hundred subjects will be randomized to the three groups. The duration of treatment will be one year, with monitoring for an additional three months. The primary outcome measure will be the one year change in the cognitive subscale of the Alzheimer's Disease Assessment Scale. Secondary outcome measures include the Clinical Dementia Rating Scale sum of boxes (CDR-SOB), the attainment of significant endpoints (death, institutionalization, 1 point worsening on the global CDR, 15 point decline on the ADCS activities of daily living (ADL) inventory), the CERAD Behavioral Rating Scale, and the ADCS global, quality of life and pharmacoeconomic scales.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AG010483-10
Application #
6315219
Study Section
Project Start
2000-07-01
Project End
2001-09-14
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
10
Fiscal Year
2000
Total Cost
$228,404
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Katsumata, Yuriko; Nelson, Peter T; Ellingson, Sally R et al. (2017) Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2. Neurobiol Aging 53:193.e17-193.e25
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
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
Spencer, Brian; Valera, Elvira; Rockenstein, Edward et al. (2017) Anti-?-synuclein immunotherapy reduces ?-synuclein propagation in the axon and degeneration in a combined viral vector and transgenic model of synucleinopathy. Acta Neuropathol Commun 5:7
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
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
Sokolow, Sophie; Li, Xiaohui; Chen, Lucia et al. (2017) Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment. J Alzheimers Dis 56:229-237
Insel, Philip S; Mattsson, Niklas; Mackin, R Scott et al. (2016) Accelerating rates of cognitive decline and imaging markers associated with ?-amyloid pathology. Neurology 86:1887-96
Ott, B R; Pelosi, M A; Tremont, G et al. (2016) A Survey of Knowledge and Views Concerning Genetic and Amyloid PET Status Disclosure. Alzheimers Dement (N Y) 2:23-29
Zlatar, Zvinka Z; Bischoff-Grethe, Amanda; Hays, Chelsea C et al. (2016) Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ?4 Allele Compared to Non-Carriers. Front Aging Neurosci 8:151

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