Effect of Daily Ingestion of Walnuts for 2 Years on Age-related Cognitive Decline and Macular Degeneration in Healthy Elderly Subjects: A Randomized, Single Blind, Dual Center, Controlled Trial
Overview
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Loma Linda University
- Enrollment
- 708
- Locations
- 2
- Primary Endpoint
- Changes from baseline in global cognitive composite score
Overview
Brief Summary
This will be a systematic investigation of the role of walnuts in preventing or slowing age related cognitive decline and age related macular degeneration. 700 subjects will be recruited between 2 sites, Loma Linda University in California, USA and Hospital Clinic in Barcelona, Spain. Participants will be randomly assigned to either the walnut group or the control group for a 2 year intervention. Baseline and annual data will be collected and analyzed.
Detailed Description
Epidemiological studies suggest that nutrients such as n-3 polyunsaturated fatty acid, antioxidants and B-vitamins may protect against age related cognitive decline. Small human studies have shown beneficial effects of polyphenol rich foods on cognition and age related macular degeneration. Walnuts are a rich source of n-3 polyunsaturated fatty acid, alpha-linolenic acid, antioxidants, polyphenols and other bioactive compounds. A 2-year intervention will be conducted with healthy, elderly subjects to investigate the role of walnuts in preventing or slowing age related cognitive decline and age related macular degeneration.
350 subjects, age 63 to 79 years, will be recruited at each of 2 sites, Loma Linda University in California and Hospital Clinic in Barcelona. Participants will be randomly assigned to one of two groups: walnut group (habitual diet with 1 or 2 oz/d walnut supplement) or control group (habitual diet only). At baseline and yearly, cardiometabolic risk factors, red blood cell membrane fatty acids, urinary polyphenols and biomarkers of inflammation and oxidation will be measured. Eye exam, blood pressure and cognitive function tests will be measured at the beginning and end of 2 years. At the Barcelona site only, participants will be given a brain MRI and carotid ultrasound.
Descriptive results will be reported as mean plus/minus standard deviation. Primary analysis will be carried out on the basis of groups as randomly assigned. Results will be presented as appropriate effect sizes with a measure of precision (95% CI). Analysis of covariates gender, age, educational status will be conducted.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Investigator)
Eligibility Criteria
- Ages
- 63 Years to 79 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •63 to 79 years old
- •healthy men and women
- •able to attend clinic at a study sites
Exclusion Criteria
- •illiteracy or inability to understand the protocol
- •unable to undergo neurophysiological tests
- •morbid obesity (BMI greater than or equal to ≥ 40 kg/m2)
- •uncontrolled diabetes (HbA1c\>85)
- •uncontrolled hypertension
- •prior cerebrovascular accident
- •any relevant psychiatric illness, including major depression
- •advanced cognitive deterioration, dementia
- •other neurodegenerative diseases (i.e. Parkinson's disease)
- •any chronic illness expected to shorten survival (heart, liver, cancer, etc)
Outcomes
Primary Outcomes
Changes from baseline in global cognitive composite score
Time Frame: 2 years
The composite score will be calculated using the scores from the tests listed below. We will calculate the standardized scores of each test as the score of each participant minus the group mean and divide by its standard deviation. The composite score is the mean of the standardized scores. The 12 tests are: Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure (ROCF), Semantic Fluency (Animals), Boston Naming Test (BNT), Visual Object and Space Perception Battery (VOSP), Block Design section from the Wechsler Adult Intelligence Scale (WAIS-III), Trail Making Test (TMT), FAS Word Fluency, Stroop Color Word Test, Symbol Digit Modalities Test (SMDT) Digit Span from the WAIS-III and Conners Continuous Performance Test (CPT-II).
Changes from baseline in macular degeneration
Time Frame: 2 years
This will be assessed: by stereoscopic digitized color fundus images graded by International Classification System for Age-Related Maculopathy (score range. 0 to 4; the higher the score, the worse the condition); by optical coherence tomography (OCT) measurements of macular thickness (in µm); by optical coherence tomography (OCT) measurements of retinal nervous fiber layer thickness (in µm).
Secondary Outcomes
- Changes from baseline in brain activation(2 years)
- Change from baseline in brain cortical thickness(2 years)
- Change from baseline in perfusion arterial spin labeling(2 years)
- Change from baseline in voxel-based morphometry(2 years)
- Change from baseline in white matter hyperintensity volumes(2 years)
Investigators
Joan Sabate,DrPH, MD
Principal Investigator, Chair, Department of Nutrition
Loma Linda University