The heterogeneous nature of the biological mechanisms associated with Alzheimer's disease (AD) pathology make therapies that can target multiple mechanisms of action rather than a single mechanism attractive candidates to delay or prevent disease progression. Oxidative stress has been highly implicated in Alzheimer's disease pathology and recent studies show there is also an association between an increase in inflammation and cholesterol (respectively), and AD pathology. Fish oil and alpha lipoic also have the ability to decrease oxidative stress, inflammation, and lipid levels, making them strong candidates as therapeutic agents in slowing the progression of Alzheimer's disease. These supplements also have few reported side effects. Based on their mechanisms of action, a combination of the two supplements has the potential to maximize the therapeutic benefit in delaying the progression in AD. The proposed study will be a pilot trial designed to collect preliminary data to aid in the design of a larger clinical trial powered to assess both treatments' effect on mechanisms associated with AD pathology and clinical markers of AD pathology. This pilot study is designed as a 3-arm, parallel group, double-blind placebo-controlled trial. Subjects >55 yrs. diagnosed with probable AD and having mild cognitive impairment will be randomized to one of three groups (13 subjects/group): 1. fish oil alone, 2. fish oil plus alpha lipoic acid, 3. placebo. The treatment intervention will be for 1-year. Our primary objective, Aim 1, is to assess the treatments' effect on oxidative stress by measuring urine F2-isoprotane levels. We will also collect preliminary data on the treatments' effect on plasma lipid levels and high-sensitivity C-reactive protein. Our secondary objective, Aim 2, is to collect preliminary data on AD-related clinical outcome measures which will include: the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinical Dementia Rating scale (CDR), Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study Activities of Daily Living Scale, SF-36, and Logical Memory I1.Our tertiary objective, Aim 3, is to assess treatment safety by a monthly monitoring of adverse events and laboratory tests (metabolic panel, including liver function tests and platelet function assay). Compliance of fish oil supplementation will be assessed by red blood cell membrane fatty acid analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG023805-01
Application #
6673510
Study Section
Special Emphasis Panel (ZAT1-K (07))
Program Officer
Buckholtz, Neil
Project Start
2003-09-30
Project End
2005-08-31
Budget Start
2003-09-30
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$179,626
Indirect Cost
Name
Oregon Health and Science University
Department
Neurology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Shinto, Lynne; Quinn, Joseph; Montine, Thomas et al. (2014) A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease. J Alzheimers Dis 38:111-20
Wang, Wei; Shinto, Lynne; Connor, William E et al. (2008) Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity. J Alzheimers Dis 13:31-8