The purpose of this study is to investigate the effects of Vitamin D3 combined with Folic Acid on mild cognitive impairment (MCI). Participants aged 50 to 70 years with MCI will be randomly assigned to three groups: a low-dose Vitamin D3 plus Folic Acid group, a high-dose Vitamin D3 plus Folic Acid group, and a placebo group. The intervention will last for 6 months. The main goal is to observe whether this nutritional intervention can improve or delay the decline of cognitive function.

Mild cognitive impairment (MCI) is a critical transitional stage between normal aging and Alzheimer's disease (AD). Designing precise dietary and nutritional interventions is a vital strategy for preventing and treating MCI. Based on an established cohort study, this randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy of combining Vitamin D3 and Folic Acid in MCI patients.

The study will analyze changes in overall and multi-dimensional cognitive functions before and after the 6-month intervention. Furthermore, the study will explore the underlying mechanisms by analyzing biological samples (blood, urine, and feces) for alterations in 27-hydroxycholesterol (27-OHC) and its metabolites, active Vitamin D3, Folic Acid levels, CYP27A1 activity, and related gene polymorphisms. The findings will help determine the optimal interaction ratio and effective dosage of this combined nutritional intervention for delaying cognitive decline.

Inclusion Criteria:

• Aged 50 to 70 years old.
• Derived from the established elderly chronic disease and health cohort.
• Meet the diagnostic criteria for Mild Cognitive Impairment (MCI) (e.g., indicated by specific cut-off scores on the MoCA adjusted for education level).
• Volunteered to participate, able to cooperate with the cognitive assessments, and signed the informed consent form.

Exclusion Criteria:

• Diagnosis of Alzheimer's disease, other types of dementia, or severe psychiatric disorders (e.g., severe depression, schizophrenia).
• History of severe neurological diseases (e.g., stroke, brain tumor, brain trauma) that may affect cognitive function.
• Severe visual or hearing impairments that prevent the completion of cognitive tests.
• Patients with liver diseases (e.g., hepatitis, liver cirrhosis) or kidney diseases (e.g., nephritis, kidney stones, renal failure).
• Patients with hypercalcemia (serum calcium concentration > 10.5 mg/dl).
• Patients with severe anemia, severe malnutrition, or abnormal thyroid function.
• Current use or use within the past 3 months of cognition-improving drugs, Vitamin D, or Folic Acid supplements, and unwilling to undergo a 3-month washout period prior to the intervention.