Brain Fog, Cognition, Long-COVID, Memory
Conditions
Brief summary
Approximately 30% of patients experience "Long-COVID" syndrome presenting with symptoms such as cognitive difficulties ('brain fog'), fatigue, dyspnea, autonomic dysfunction, depression and anxiety, lasting beyond 12 weeks causing significant disability, and threaten health and wellbeing of millions around the world. At the current time, there is no effective treatment for long-COVID. Walnuts contain a mixture of nutrients and phytochemicals include monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and alpha-linolenic acid (ALA). Walnut consumption was directly associated with cognitive function. The investigators have shown pomegranate that share the same phytonutrient ellagitannins as walnut and mixed nuts including walnuts could increase blood microbiome metabolites of tryptophan metabolite indole propionate and serotonin levels via change of gut microbiota and therefore play an essential role in gut-brain axis including cognitive function. The proposed pilot study will include 76 adults (ages \>40 years) with diagnosis of SARS-CoV2 infection presenting with long-COVID symptoms lasting longer than 12 weeks. They will be randomized 1:1 to usual care vs. an intervention group that will include 2 oz (57g) of walnuts daily into their habitual diet for 12 weeks. The investigators will compare the improvement in symptoms of cognitive complains of "brain fog", fatigue and depression of the active intervention group vs. usual care. The outcome of the investigation of the benefit of walnut consumption will provide important novel information on using dietary sources of polyunsaturated fatty acids and phytochemicals to mitigate the common symptoms of long-COVID. This application was submitted in response to the California Walnut Commission's commodity board topic.
Interventions
OTHERwhole food - walnuts
Participants randomized to the intervention group will consume (2 oz ) of whole walnuts daily, incorporated into their diet for 12 weeks. Walnuts were provided to participants, and adherence was monitored using dietary records.
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age 40 years and older History of confirmed SARS-CoV-2 infection Presence of long-COVID symptoms lasting longer than 12 weeks, including one or more of the following: * Cognitive complaints ("brain fog," memory, attention, or processing speed difficulties) * Fatigue * Mood symptoms (e.g., depression) Consumption of a low-polyphenol (Western) diet Adequate visual acuity and hearing to complete neuropsychological testing Screening laboratory results without clinically significant abnormalities that would interfere with study participation Ability and willingness to provide written informed consent
Exclusion criteria
Diagnosis of probable Alzheimer's disease or other dementia (e.g., vascular, Lewy body, frontotemporal) Other neurological or medical conditions that may cause cognitive impairment Evidence of Parkinson's disease based on motor examination Uncontrolled hypertension (systolic BP \>170 mmHg or diastolic BP \>100 mmHg) Allergy to walnuts Regular consumption of more than 5 oz of walnuts per week Current diagnosis of a major psychiatric disorder according to DSM-5 criteria Alcoholism or substance use disorder Any condition that, in the investigator's judgment, would make participation unsafe or interfere with study completion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Episodic Memory - RAVLT-Revised Long-Delay Free Recall (number of words recalled) | Baseline to Week 12 | Change in long-delay free recall score (number of words correctly recalled) on the RAVLT-Revised from baseline to week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | Baseline and Week 12 | Seated systolic and diastolic blood pressure Systolic and diastolic blood pressure will be measured in millimeters of mercury (mmHg) using an automated calibrated sphygmomanometer after 5 minutes of seated rest. Higher values indicate higher blood pressure. |
| Dietary Intake | Baseline and 12 | 24-hour dietary recall (ASA24™) |
| NIH Toolbox Cognitive Battery (NIHTB-CB) - Fluid Intelligence Composite | Baseline to Week 12 | Fluid cognitive function will be assessed using the Fluid Intelligence Composite score from the NIH Toolbox Cognitive Battery. The composite is a standardized score (mean = 100, SD = 15), with higher scores indicating better cognitive performance. |
| Quality of Life | Baseline and 12 | SF-36 Health Survey |
| WAIS-IV Symbol Search Score | Baseline and 12 weeks | Total correct responses (scaled score) on the WAIS-IV Symbol Search subtest, assessing processing speed. |
| Executive Function | Baseline to Week 12 | Digit Vigilance Test Score Description: Total completion time (seconds) and/or number of errors on the Digit Vigilance Test, assessing sustained attention and processing speed. |
| Trail Making Test Part A Completion Time | baseline and 12 weeks | Description: Time to completion (seconds) for Trail Making Test Part A, assessing processing speed. |
| Fatigue | Baseline and 12 | Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue Short Form - 8 Item. Fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue Short Form (8 items). Raw scores range from 8 to 40, with higher scores indicating greater fatigue (worse outcome). Scores may also be converted to standardized T-scores (mean = 50, SD = 10), where higher T-scores indicate greater fatigue. |
| Mood | baseline and 12 weeks | PROMIS® Depression Short Form (8 items) |
| Heart Rate | Baseline and Week 12 | Resting heart rate Description: Resting heart rate will be measured in beats per minute (bpm) using an automated blood pressure monitor after 5 minutes of seated rest. |
| Blood and Urine Biomarkers | Baseline, 12 Weeks | Measures: metabolic markers and inflammatory Blood fatty acid profile Plasma ellagic acid Urinary urolithin metabolites (LC-MS/MS) |
| Body Weight | baseline and week 12 | Measure: Body weight in kilograms Description: Body weight will be measured in kilograms (kg) using a calibrated digital scale with participants wearing light clothing and no shoes. |
Countries
United States
Outcome results
None listed