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NCT Number: NCT07272174

Exercise in Perimenopause to Improve Cognitive Health

Perimenopause is now considered a possible risk factor for dementia and may contribute to the fact that 2/3 of those living with Alzheimer's disease are females. Indeed, research studies show that middle-aged females demonstrate significant declines in their thinking abilities and detrimental changes in their brains as they go through perimenopause. Thus, perimenopausal females need strategies to bolster their brain health.

The World Health Organization strongly recommends physical activity interventions to reduce the risk of decline in thinking abilities. However, whether exercise can improve thinking abilities and brain health in perimenopausal females has not been examined. Our research aims to address this important knowledge gap in female brain health.

We will study the effects of a 6-month resistance exercise training (e.g., lifting free weights, exercise with weight machine) program on thinking abilities in 50 physically inactive perimenopausal females, aged 40 to 55 years, who are experiencing difficulties with their thinking abilities. In addition to measuring thinking abilities, we will determine if exercise benefits muscle health, heart health, sleep quality, psychological well-being, menopausal symptoms, and quality of life. We will also explore how resistance exercise training improves thinking abilities as such information can lead to new discoveries and therapies for brain health in females.

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Key information

Age range

40 year–55 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location status: Recruiting

Location contact

Teresa Liu-Ambrose, MHK

CONTACT

[email protected]

604-875-4111 ext. 69059

About this study

  • PURPOSE:

To determine if progressive resistance training (PRT) can improve cognitive outcomes compared to balance, flexibility, and tone (BAT) exercises in perimenopausal females aged 40-55 years with subjective cognitive complaints.

  • HYPOTHESIS:

At the end of the intervention, PRT will result in an increase in words recalled during the RAVLT 20-minute delay vs no improve in BAT.

  • JUSTIFICATION:

The menopause transition (MT) negatively impacts cognitive function and the brain. The majority of perimenopausal females experiences cognitive difficulties and have subjective cognitive complaints (SCCs). Verbal episodic memory and processing speed are most negatively impacted by the MT. Cognitive and brain changes during the MT can significantly impact career and financial wellbeing. The MT is thus a critical window to intervene for female brain health. Exercise can reduce dementia risk factors and promote cognitive health. No published randomized controlled trials have examined the effect of exercise on cognitive outcomes in perimenopausal females.

  • OBJECTIVE:

To determine if 26 weeks of 2x/week progressive resistance training (PRT) can improve verbal episodic memory performance on the Rey Auditory Verbal Learning Test (RAVLT) compared with balance, flexibility, and tone exercises (BAT) for physically inactive perimenopausal females aged 40-55.

  • RESEARCH DESIGN:

A 26-week, assessor-blinded, two-arm, proof-of-concept trial with 50 physically inactive perimenopausal females, aged 40 to 55 years, with subjective cognitive complaints. Participants will be randomized 1:1 to PRT or BAT and measured at baseline, 13 weeks, and 26 weeks.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Are biological females, as assigned at birth
  • Are aged between 40 and 55 years
  • Had at least 1 menstrual period in the last 10 months
  • Are perimenopausal based on STRAW +10 Staging System, or answer "yes" to MQ6 questions of changes in periods, having hot flashes, or vaginal dryness, pain, or sexual concerns
  • Have an intact uterus
  • Have a Montreal Cognitive Assessment (MoCA) score >26/30, indicating normal cognition
  • Have subjective cognitive complaints defined as responding "yes" to "Do you feel like your memory or thinking is becoming worse?"
  • Completed high school education
  • Read and speak English with acceptable visual and auditory acuity
  • Are able to safely engage in moderate-intensity PRT as indicated by the PAR-Q+; and
  • Are able to provide informed consent.

Exclusion criteria

  • Are engaged in regular PRT (i.e., 2x/week) in the prior three months
  • Are diagnosed with cognitive impairment or dementia of any type
  • Are at high risk for cardiac complications during exercise
  • Have clinically important peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility
  • Are taking medications that negatively affect cognitive function, such as anticholinergics, major tranquilizers, and anticonvulsants
  • Have a BMI <15 or anorexia nervosa; g) had surgical menopause
  • Had endometrial ablation that resulted in the loss of menstruation
  • Have polycystic ovarian syndrome
  • Currently undergoing chemo
  • Are using estrogen-containing contraception in the last 12 months
  • Had premature ovarian failure; or
  • Are already enrolled in a drug or exercise trial

Treatment and study plan

Progressive resistance training

Behavioral

The sessions will occur in the Exercise Prescription Suite of the Centre for Aging SMART at VCH; this suite is a fully-equipped gym that includes treadmills, bikes, pneumatic resistance training equipment, and free weights. The training stimulus will initially be at 3 sets of 10-15 repetitions with proper form. At week 4, training intensity will progress from 60-82% of predicted 1 repetition maximum (RM) using the 8RM method. Every 4 weeks the 8RM test will be repeated.

Other names: PRT

Balance, Flexibility, and Tone Exercises

Behavioral

Each BAT session will be 1-hr in duration and consist of Pilates mat exercises, Yoga-based poses and breathing, Kegel exercises, stretches, and relaxation techniques (e.g., visualization).

Other names: BAT

Primary outcomes

  1. Rey Auditory Verbal Learning Test (RAVLT)

    Time frame: Baseline, 13 weeks, 26 weeks

    The RAVLT is a valid, reliable, and widely-used instrument of verbal episodic memory and learning, with normative values.

Secondary outcomes

  1. NIH TB Cognitive Battery - Flanker Test

    Time frame: Baseline, 13 weeks, 26 weeks

    A measure of executive functions

  2. NIH TB Cognitive Battery - Dimensional Change Card Sort Test

    Time frame: Baseline, 13 weeks, 26 weeks

    A measure of executive functions

  3. NIH TB Cognitive Battery - Picture Sequence Memory Test

    Time frame: Baseline, 13 weeks, 26 weeks

    A measure of visual episodic memory

  4. NIH TB Cognitive Battery - List Sorting Test

    Time frame: Baseline, 13 weeks, 26 weeks

    A measure of working memory

  5. NIH TB Cognitive Battery - Pattern Comparison Processing Speed Test

    Time frame: Baseline, 13 weeks, 26 weeks

    A measure of processing speed

  6. Everyday Memory Questionnaire

    Time frame: Baseline, 13 weeks, 26 weeks

    A subjective measure of memory failure in everyday life

  7. Muscle strength of quads

    Time frame: Baseline, 13 weeks, 26 weeks

    Muscle strength measure by isokinetic dynamometer

  8. Peripheral QCT of the tibia

    Time frame: Baseline, 13 weeks, 26 weeks

    A measure of bone and muscle health

  9. Blood pressure

    Time frame: Baseline, 13 weeks, 26 weeks

    Blood pressure - systolic and diastolic

  10. Lipid panel

    Time frame: Baseline, 26 weeks

    Lipid levels

  11. Hemoglobin A1-C

    Time frame: Baseline, 26 weeks

    Average blood sugar levels

  12. C-reactive protein

    Time frame: Baseline, 26 weeks

    Measure of inflammation

  13. Health resource utilization

    Time frame: Baseline, 13 weeks, 26 weeks

    Cost of health resource used

  14. Carotid-femoral pulse wave velocity

    Time frame: Baseline, 13 weeks, 26 weeks

    Arterial stiffness

  15. Pittsburgh Sleep Quality Index

    Time frame: Baseline, 13 weeks, 26 weeks

    Subjective sleep quality

  16. Actigraph

    Time frame: Baseline, 13 weeks, 26 weeks

    Using actigraphy data, quantify sleep quality (e.g., duration, efficiency, fragmentation).

  17. Actigraph

    Time frame: Baseline, 13 weeks, 26 weeks

    Using actigraphy data, quantify physical activity (e.g., intensity and minutes)

  18. Actigraph

    Time frame: Baseline, 13 weeks, 26 weeks

    Using actigraphy data, quantify sedentary behaviour (minutes)

  19. Fatigue Severity Scale

    Time frame: Baseline, 13 weeks, 26 weeks

    Subjective fatigue

  20. PHQ-9

    Time frame: Baseline, 13 weeks, 26 weeks

    Depression severity

  21. GAD-7

    Time frame: Baseline, 13 weeks, 26 weeks

    Generalized anxiety disorder

  22. Menopause Rating Scale

    Time frame: Baseline, 13 weeks, 26 weeks

    Menopause symptoms

  23. EuroQol-5 Domain-5 Level

    Time frame: Baseline, 13 weeks, 26 weeks

    Quality of life

  24. International Physical Activity Questionnaire

    Time frame: Every 30 days over 26 weeks

    Physical activity

  25. DEXA

    Time frame: Baseline, 13 weeks, 26 weeks

    Lean mass

  26. DEXA

    Time frame: Baseline, 13 weeks, 26 weeks

    Body fat

  27. DEXA

    Time frame: Baseline, 13 weeks, 26 weeks

    Appendicular Skeletal Muscle Mass Index (ASMI); a measure of sarcopenia

  28. Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) Diet score

    Time frame: Baseline, 13 weeks, 26 weeks

    Diet

  29. Processing Speed by smartphone

    Time frame: Baseline, 13 weeks, 26 weeks

    Processing Speed

  30. Memory by smartphone

    Time frame: Baseline, 13 weeks, 26 weeks

    Memory

  31. Productivity Questionnaire

    Time frame: Baseline, 13 weeks, 26 weeks

    Measure of work productivity

  32. Brain-Derived Neurotrophic Factor

    Time frame: Baseline, 26 weeks

    Neurotrophic Factor

  33. IGF-1

    Time frame: Baseline, 26 weeks

    Neurotrophic Factor

Study contacts

Contact information is provided by the study sponsor or research team.

Teresa Liu-Ambrose, PhD

CONTACT

[email protected]

6046178047

Sponsors and collaborators

Lead sponsor

University of British Columbia

Other

Collaborators

  • Vancouver Coastal Health Research Institute

Registry information

Official study title

Resistance Training and Cognitive Health in Perimenopause

Acronym: EPIC

Important dates

Study start
2026
Primary completion
2026
Study completion
2027
First posted
Dec 9, 2025
Registry last updated
Apr 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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