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.

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).

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.