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Age Related Cognitive DeclineWAHANCT01634841

Walnuts and Healthy Aging

A study testing Walnuts and habitual diet in people with Age Related Cognitive Decline and Age Related Macular Degeneration, run by Loma Linda University at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 63 to 79 yearsHealthy volunteers can take part
What is being tested?
Walnuts and habitual diet
Could I receive a placebo?
No, everyone receives an active treatment
How many people
708 participants
Where
2 sitesin 2 countries
Study dates
Apr 2012to May 2016
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 63 to 79 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 63 to 79 years old
  • healthy men and women
  • able to attend clinic at a study sites

Who cannot join

  • 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
Show all 15Show fewer
  • 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)
  • bereavement in the first year of loss
  • bad dentures unless fixable dental prostheses are used
  • allergy to walnuts
  • customary us of fish oil or flaxseed oil supplements
  • eye related exclusion criteria

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Loma Linda University, Department of Nutrition

    Loma Linda, California, 92350

Other trials in United States

Spain1 site

  • Hospital Clinic, University of Barcelona

    Barcelona, 08036

Other trials in Spain

About this study

Official title: 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

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.

Read the 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.

Being tested
Walnuts, habitual diet
Keywords
walnuts, age related cognitive decline, age related macular degeneration, healthy elderly subjects
Medical subject headings
Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • WalnutsDietary supplement

    30 to 60g (1 to 2 oz) per day of walnuts

  • habitual dietOther

    Dietary information will be provided

Study groups in NCT01634841
Study groupRoleWhat they receive
Walnut groupActive comparatorThis group will have their habitual diet supplemented with 30 to 45g (1 to 1.5 oz) of walnuts daily.
Receives: Dietary Supplement: Walnuts
Control groupActive comparatorThis group will eat their habitual diet and refrain from eating walnuts.
Receives: Other: habitual diet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes from baseline in global cognitive composite score

    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).

    Measured: 2 years

  2. Changes from baseline in macular degeneration

    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).

    Measured: 2 years

Secondary outcomes (5)

  1. Change from baseline in brain cortical thickness

    Changes will be assessed by brain magnetic resonance imaging (MRI) on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is mm2.

    Measured: 2 years

  2. Change from baseline in voxel-based morphometry

    Changes will be assessed by brain magnetic resonance imaging (MRI) using GM density maps on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is GM density.

    Measured: 2 years

  3. Change from baseline in white matter hyperintensity volumes

    Changes will be assessed by brain magnetic resonance imaging (MRI) on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is mL.

    Measured: 2 years

  4. Change from baseline in perfusion arterial spin labeling

    Changes will be assessed by brain magnetic resonance imaging (MRI) on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is ml/100 g/min.

    Measured: 2 years

  5. Changes from baseline in brain activation

    Changes will be assessed by Functional MRI (fMRI) on a randomly selected subset of participants. Only in Barcelona center. There are no units of measure.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionMay 2016
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Investigator
Enrolment
708 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01634841
Sponsor's protocol ID
5120066
Other IDs
670715-3833
Acronym
WAHA
Status last verified
Jun 2021
First submitted
20 Jun 2012
Last updated
24 Jun 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Galkina P, Dominguez-Lopez I, Cofan M, Pozzoli C, Vallverdu-Queralt A, Serra-Mir M, Chiva-Blanch G, Rajaram S, Sabate J, Sala-Vila A, Ros E, Lamuela-Raventos RM. Microbiota-derived urolithins and cortical thickness in cognitively healthy older adults: a longitudinal MRI analysis of the WAHA trial. Food Funct. 2026 Oct 7. doi: 10.1039/d6fo02116f. Online ahead of print.

    PubMed 42841852

  • Soldevila-Domenech N, Ayala-Garcia A, Zhou X, Yi SY, Ros E, Sala-Vila A, Lehtisalo J, Steffen LM, de la Torre R; IAFNS Retrospective Harmonization Expert Working Group. Diet and Cognitive Function in Aging: An Individual Participant Data Meta-Analysis from 8 Cohorts in Europe and the United States. J Nutr. 2026 Jun 29;156(9):101694. doi: 10.1016/j.tjnut.2026.101694. Online ahead of print.

    PubMed 42373047

  • Cofan M, Checa A, Serra-Mir M, Roth I, Valls-Pedret C, Lopez-Illamola A, Domenech M, Rajaram S, Lazaro I, Sabate J, Ros E, Wheelock CE, Sala-Vila A. A Walnut-Enriched Diet for 2 Years Changes the Serum Oxylipin Profile in Healthy Older Persons. J Nutr. 2024 Feb;154(2):395-402. doi: 10.1016/j.tjnut.2023.12.007. Epub 2023 Dec 9.

    PubMed 38081585

  • Fjell AM, Sorensen O, Wang Y, Amlien IK, Baare WFC, Bartres-Faz D, Boraxbekk CJ, Brandmaier AM, Demuth I, Drevon CA, Ebmeier KP, Ghisletta P, Kievit R, Kuhn S, Madsen KS, Nyberg L, Sole-Padulles C, Vidal-Pineiro D, Wagner G, Watne LO, Walhovd KB. Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers. J Neurosci. 2023 Jul 12;43(28):5241-5250. doi: 10.1523/JNEUROSCI.2330-22.2023. Epub 2023 Jun 26.

    PubMed 37365003

  • Nyberg L, Magnussen F, Lundquist A, Baare W, Bartres-Faz D, Bertram L, Boraxbekk CJ, Brandmaier AM, Drevon CA, Ebmeier K, Ghisletta P, Henson RN, Junque C, Kievit R, Kleemeyer M, Knights E, Kuhn S, Lindenberger U, Penninx BWJH, Pudas S, Sorensen O, Vaque-Alcazar L, Walhovd KB, Fjell AM. Educational attainment does not influence brain aging. Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2101644118. doi: 10.1073/pnas.2101644118.

    PubMed 33903255

  • Fjell AM, Sorensen O, Amlien IK, Bartres-Faz D, Brandmaier AM, Buchmann N, Demuth I, Drevon CA, Duzel S, Ebmeier KP, Ghisletta P, Idland AV, Kietzmann TC, Kievit RA, Kuhn S, Lindenberger U, Magnussen F, Macia D, Mowinckel AM, Nyberg L, Sexton CE, Sole-Padulles C, Pudas S, Roe JM, Sederevicius D, Suri S, Vidal-Pineiro D, Wagner G, Watne LO, Westerhausen R, Zsoldos E, Walhovd KB. Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium. Cereb Cortex. 2021 Mar 5;31(4):1953-1969. doi: 10.1093/cercor/bhaa332.

    PubMed 33236064

  • Sorensen O, Brandmaier AM, Macia D, Ebmeier K, Ghisletta P, Kievit RA, Mowinckel AM, Walhovd KB, Westerhausen R, Fjell A. Meta-analysis of generalized additive models in neuroimaging studies. Neuroimage. 2021 Jan 1;224:117416. doi: 10.1016/j.neuroimage.2020.117416. Epub 2020 Oct 2.

    PubMed 33017652

  • Hooper L, Martin N, Jimoh OF, Kirk C, Foster E, Abdelhamid AS. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2020 Aug 21;8(8):CD011737. doi: 10.1002/14651858.CD011737.pub3.

    PubMed 32827219

  • Hooper L, Martin N, Jimoh OF, Kirk C, Foster E, Abdelhamid AS. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2020 May 19;5(5):CD011737. doi: 10.1002/14651858.CD011737.pub2.

    PubMed 32428300

  • Sala-Vila A, Valls-Pedret C, Rajaram S, Coll-Padros N, Cofan M, Serra-Mir M, Perez-Heras AM, Roth I, Freitas-Simoes TM, Domenech M, Calvo C, Lopez-Illamola A, Bitok E, Buxton NK, Huey L, Arechiga A, Oda K, Lee GJ, Corella D, Vaque-Alcazar L, Sala-Llonch R, Bartres-Faz D, Sabate J, Ros E. Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts And Healthy Aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr. 2020 Mar 1;111(3):590-600. doi: 10.1093/ajcn/nqz328.

    PubMed 31912155

  • Bartres-Faz D, Gonzalez-Escamilla G, Vaque-Alcazar L, Abellaneda-Perez K, Valls-Pedret C, Ros E, Grothe MJ. Characterizing the Molecular Architecture of Cortical Regions Associated with High Educational Attainment in Older Individuals. J Neurosci. 2019 Jun 5;39(23):4566-4575. doi: 10.1523/JNEUROSCI.2370-18.2019. Epub 2019 Apr 8.

    PubMed 30962275

  • Domenech M, Serra-Mir M, Roth I, Freitas-Simoes T, Valls-Pedret C, Cofan M, Lopez A, Sala-Vila A, Calvo C, Rajaram S, Sabate J, Ros E. Effect of a Walnut Diet on Office and 24-Hour Ambulatory Blood Pressure in Elderly Individuals. Hypertension. 2019 May;73(5):1049-1057. doi: 10.1161/HYPERTENSIONAHA.118.12766.

    PubMed 30879358

  • Freitas-Simoes TM, Cofan M, Blasco MA, Soberon N, Foronda M, Corella D, Asensio EM, Serra-Mir M, Roth I, Calvo C, Valls-Pedret C, Casaroli-Marano RP, Domenech M, Rajaram S, Sabate J, Ros E, Sala-Vila A. The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial. Clin Nutr. 2019 Apr;38(2):958-961. doi: 10.1016/j.clnu.2018.02.011. Epub 2018 Feb 17.

    PubMed 29478886

  • Rajaram S, Valls-Pedret C, Cofan M, Sabate J, Serra-Mir M, Perez-Heras AM, Arechiga A, Casaroli-Marano RP, Alforja S, Sala-Vila A, Domenech M, Roth I, Freitas-Simoes TM, Calvo C, Lopez-Illamola A, Haddad E, Bitok E, Kazzi N, Huey L, Fan J, Ros E. The Walnuts and Healthy Aging Study (WAHA): Protocol for a Nutritional Intervention Trial with Walnuts on Brain Aging. Front Aging Neurosci. 2017 Jan 10;8:333. doi: 10.3389/fnagi.2016.00333. eCollection 2016.

    PubMed 28119602

  • Fernandez-Cabello S, Valls-Pedret C, Schurz M, Vidal-Pineiro D, Sala-Llonch R, Bargallo N, Ros E, Bartres-Faz D. White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults. Neurobiol Aging. 2016 Dec;48:23-33. doi: 10.1016/j.neurobiolaging.2016.08.008. Epub 2016 Aug 20.

    PubMed 27636672

Questions about this trial

What is this clinical trial studying?

A study testing Walnuts and habitual diet in people with Age Related Cognitive Decline and Age Related Macular Degeneration, run by Loma Linda University at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes from baseline in global cognitive composite score (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01634841, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2021.

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