Effects of Mediterranean Diet on Subjective Cognitive Decline

Effects of Mediterranean Diet on Physical and Cognitive Functions in Community-dwelling Older People With Subjective Cognitive Decline - a Randomized Controlled Cross-over Trial

Research Questions:

1. Due to the fact that most participants in past clinical trials on the Mediterranean diet were cognitively healthy individuals, and while the observed effects were significant, they were not particularly substantial, does the Mediterranean diet have similarly significant and more pronounced effects on both physical and cognitive functions in older adults with subjective cognitive decline (SCD)?
2. What is the mechanism behind the effects of the Mediterranean diet on physical or/and cognitive function? Is it through vascular protection or improvements in brain structure/brain network function?

Research Objective:

Conduct a cross-over randomized controlled trial to investigate the effects of a three-month Mediterranean diet on the physical and cognitive functions of older adults with subjective cognitive decline (SCD) in the community. Utilize brain MRI and circulatory biomarkers measurements to elucidate the underlying mechanisms.

Study Overview

• Status: Recruiting
• Conditions: Subjective Cognitive Decline
• Intervention / Treatment: Other: Mediterranean diet; Other: Regular diet

Detailed Description

Research Questions:

1. Due to the fact that most participants in past clinical trials on the Mediterranean diet were cognitively healthy individuals, and while the observed effects were significant, they were not particularly substantial, does the Mediterranean diet have similarly significant and more pronounced effects on both physical and cognitive functions in older adults with subjective cognitive decline (SCD)?
2. What is the mechanism behind the effects of the Mediterranean diet on physical or/and cognitive function? Is it through vascular protection or improvements in brain structure/brain network function?

Research Objective:

Conduct a randomized controlled trial to investigate the effects of a three-month Mediterranean diet on the physical and cognitive functions of older adults with subjective cognitive decline (SCD) in the community. Utilize brain MRI to elucidate the underlying mechanisms.

Participants inclusion criteria:

SCD-plus subjects must fullfill the following five criteria

1. Subjective memory decline without impairment in other cognitive domains (MMSE > 26; MMSE > 14 for those with less than six years of education).
2. Onset of subjective cognitive decline within the past 5 years.
3. Age at the onset of subjective cognitive decline is greater than 60 years.
4. Concern and preoccupation with the decline in memory.

5. Perceived functional decline relative to peers and meet one of the following three criteria:

   1. Caregiver perceives cognitive decline.
   2. Carries the APOE ε4 genotype.
   3. Clinical evidence of preclinical Alzheimer's disease biomarkers.

Participants exclusion criteria:

1. Cases unable to comply with or accept the dietary intervention, including individuals with dietary restrictions such as vegetarianism, lactose intolerance, or potential food allergies.
2. Walking speed ≤ 0.3 meters/second.

3. Any significant medical conditions affecting physical and cognitive functions, including:

   1. Limb fracture within the past six months.
   2. Severe arthritis within the past six months.
   3. Neurological and psychiatric disorders as determined by the principal investigator (e.g., stroke, Parkinson's disease, peripheral neuropathy, mental disorders).
   4. Intermittent claudication due to peripheral arterial disease.
4. Chronic kidney disease (eGFR <30 ml/min/1.73m2) and individuals undergoing dialysis.
5. Poorly controlled cardiovascular diseases as determined by the principal investigator.
6. Poorly controlled malignant tumors as determined by the principal investigator.
7. Severe visual and hearing impairments preventing the completion of assessments and tests.
8. Participants who have undergone hormone therapy in the three months preceding the trial or are expected to undergo hormone therapy during the trial.

Study Design or Implementation:

This study is a cross-over (three month of Mediterranean diet phase "M" and three month of regular diet phase "R") randomized controlled trial with a duration of six to seven months (seven month for MR group with an additional one-month washout period). During the study period, participants in the M phase will receive a daily portion of a Mediterranean diet designed by a nutritionist. Regular Mediterranean diet education and reviews will be conducted to ensure that the Mediterranean Diet Score System (MDSS) reaches a score of ≥10. The R phase will follow a self-selected diet, and the MDSS during then will also be assessed.

Eligible participants will be randomly assigned to two groups with different diet sequences (MR or RM group) in a 1:1 ratio. T0 measurements will be conducted, including a basic information questionnaire, blood biomarker sampling for Alzheimer's disease, and the initial assessment of physical and cognitive functions. Dietary assessments and education will be conducted before entering the dietary intervention group and at one week, two weeks, one month, two months, and three months after entering each phase. Other measurements, including blood pressure, heart rate, height and weight measurements, blood tests, and brain MRI, will be performed at T1 and T2 (end of each diet phase).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chih-Ping Chung, MD PhD; Phone Number: +886-2-918155976; Email: pin324pin324@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Chih-Ping Chung, MD PhD; Phone Number: +886-2-918155976; Email: pin324pin324@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subjective cognitive decline (SCD)-plus subjects, individuals must meet five criteria:

1. Subjective memory decline without impairment in other cognitive domains (MMSE > 26; MMSE > 14 for <6 years of education).
2. Onset of subjective cognitive decline within the past 5 years.
3. Age at the onset of subjective cognitive decline is >60 years.
4. Concern and preoccupation with memory decline.
5. Perceived functional decline relative to peers and meet one of three criteria: a. Caregiver perceives cognitive decline; b. Carries APOE ε4 genotype; c. Clinical evidence of preclinical Alzheimer's disease biomarkers.

Exclusion Criteria:

Exclude individuals who:

1. Cannot comply with or accept the dietary intervention (e.g., dietary restrictions, vegetarianism, lactose intolerance).
2. Have walking speed ≤ 0.3 meters/second.
3. Have significant medical conditions affecting physical and cognitive functions.
4. Have chronic kidney disease (eGFR <30 ml/min/1.73m2) or undergo dialysis.
5. Experience poorly controlled cardiovascular diseases or malignant tumors.
6. Have severe visual and hearing impairments preventing assessments.
7. Have undergone hormone therapy in the preceding three months or are expected to during the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Mediterranean diet phase followed by regular diet phase; Three-month of M phase, one month of washout and three month of R phase	Other: Mediterranean diet; Mediterranean diet for three month; Other: Regular diet; regular diet
Other: Regular diet phase followed by Mediterranean diet phase; Three-month of R phase followed by three month of M phase	Other: Mediterranean diet; Mediterranean diet for three month; Other: Regular diet; regular diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive functional change	Subjective and objective cognitive functional measurements (MMSE and comprehensive neuropsychological tests for verbal memory, attention, visuospatial function, executive function, and language)	Three month of allocated diet phase
Physical function 1 - gait speed change	Gait speed measurements	Three month of allocated diet phase
Physical function 2 - handgrip strength change	Handgrip strength measurements	Three month of allocated diet phase
Physical function 3 - stand from chair speed change	Five times of stand from chair speed measurements	Three month of allocated diet phase
Brain MRI structural change - total and regional voxel-based brain parenchymal features change	Brain gray matter/white matter volumes and diffusion tensor imaging measurements	Three month of allocated diet phase
Brain MRI functional change - total and regional voxel-based brain functional features change	Resting functional MRI signal analsyes	Three month of allocated diet phase
Brain MRI neurovascular lesion change - small vessel disease markers	white matter hyperintensities, lacune and cerebral microbleeds assessments	Three month of allocated diet phase
Brain MRI neurovascular structural change - microvascular density	arteriolar and venular densities	Three month of allocated diet phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AD circulatory biomarkers	Amyloid beta 40/42, p-tau-217, NfL, TDP43,ASC level changes	Three month of allocated diet phase

Collaborators and Investigators

• Sponsor: Chih-Ping Chung
• Collaborators: National Yang Ming Chiao Tung University
• Investigators: Principal Investigator: Chih-Ping Chung, MD PhD, Department of Neurology, Neurological Institute, Taipei Veterans General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 16, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Estimated): March 1, 2024

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: No.:2023-08-010ACF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No