Time-Restricted Eating in Combination With a Low Glycaemic Index Diet on Cognitive Function, Biological Ageing and Metabolic Health in Perimenopause and Menopause.

This randomized controlled trial will run over a period of 24 weeks (6 months) and will be divided into two main phases: a 12-week intervention phase followed by a 12- week follow-up phase designed to assess long-term adherence and health outcomes. The participants will be randomized to one of two groups: the intervention group of a Time-Restricted Eating combined with a Low Glycaemic Index diet (TRE-LGI) group, and the control group which will not receive any dietary intervention.

During the intervention phase (Week 0 to Week 12), participants randomized to the TRE-LGI group will follow a structured eating plan. They will be instructed to consume all their meals within an 8-hour eating window each day and adhere to a low glycaemic index Mediterranean-style diet. Participants randomized to the control group will not receive any dietary intervention but will continue to be monitored for study purposes.

Assessments will be conducted at three time points during this phase. At baseline (Week 0), participants will complete a full set of evaluations, including the online Computerised Neurocognitive Testing tool CNS Vital Signs, metabolic markers (insulin sensitivity, and lipid profiles, C-reactive protein (CRP), BDNF assessment using Enzyme-Linked Immunosorbent Assay (ELISA) Test, biological ageing assessment using the N-glycome analysis (GlycanAge test), gut microbiome analysis from stool samples, body composition, blood pressure, waist circumference, sleep quality using the Pittsburgh Sleep Quality Index (PSQI), physical activity using the International Physical Activity Questionnaire-Short Form IPAQ-SF, tender and swollen joint count and Global Health using the PROMIS® Scale v1.2 - Global Health.

At Week 6, only the N-glycome composition analysis (GlycanAge) will be repeated to monitor changes in biological ageing.

At Week 12, all baseline assessments will be repeated to measure the effects of the intervention.

The follow-up phase, spanning from week 12-24, will focus on evaluating the participants' ability to sustain the dietary practices achieved during the intervention period without receiving further active dietary guidance. Monitoring will continue to measure the longer-term effects on cognitive, metabolic, and biological health outcomes.

At Week 18, participants will undergo N-glycome composition analysis (GlycanAge) to continue monitoring biological ageing.

At Week 24, a final comprehensive assessment will be conducted, including cognitive function (CNS Vital Signs), BDNF Test, N-glycome analysis, body composition using BIA, BMI, blood pressure, waist circumference, and sleep quality (PSQI), physical activity (IPAQ-SF), tender and swollen joint count, and Global Health PROMIS questionnaire.

Participants in the control group will complete the same assessments at each scheduled time point, allowing for direct comparisons; however, they will not undergo any dietary intervention throughout the study.

Inclusion criteria

• Women in late perimenopausal or menopausal status Note: Late perimenopause is defined as two or more skipped cycles and at least 60 days of amenorrhea. Recent blood tests showing elevated FSH levels support eligibility for late perimenopause. Menopause is defined as 12 consecutive months without a menstrual cycle.
• BMI ≥23 kg/m2
• Age 45-75 years old
• If using any medication, the dose should be stable for the previous 12 months
• Able to use technology and follow the dietary plan

Exclusion criteria

• Diagnosis of mild cognitive impairment (MCI) or Alzheimer's disease (AD). Note: (Self-reported memory complaints are allowed).

• On hormone replacement therapy (HRT)
• Medical conditions that significantly affect cognitive or metabolic function including diagnosis of type 1 diabetes, severe metabolic disorders, cardiovascular disease, or neurodegenerative conditions, diagnosed eating disorders or severe mental health conditions.
• Currently enrolled in another intervention.
• Severe food allergies or dietary restrictions that would prevent adherence to the study diet.
• History of substance abuse.