Exercise in Perimenopause to Improve Cognitive Health (EPIC)

Resistance Training and Cognitive Health in Perimenopause

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.

Study Overview

• Status: Recruiting
• Conditions: Perimenopause; Subjective Cognitive Complaints
• Intervention / Treatment: Behavioral: Progressive Resistance Training; Behavioral: Balance, Flexibility, and Tone Exercises

Detailed Description

1. 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.

2. 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.

3. 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.

4. 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.

   Optional Qualitative Component: To assess knowledge and experiences of perimenopause (pre- and post-intervention), expectations of exercise intervention (pre-intervention), and perceived benefits of exercise intervention (post-intervention).

5. 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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Teresa Liu-Ambrose, PhD; Phone Number: 6046178047; Email: teresa.ambrose@ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • University of British Columbia
      • Contact: Teresa Liu-Ambrose, MHK; Phone Number: 69059 604-875-4111; Email: teresa.ambrose@ubc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 for in-person or >=19/22 for telephone , 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Progressive Resistance Training (PRT); Each PRT session will be 1-hr in duration and consists of a warm-up (10 mins), PRT (45 mins), and cool-down (5 mins). 2x/week and group-based.	Behavioral: Progressive Resistance Training; 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
Active Comparator: Balance, Flexibility, and Tone Exercises (BAT); Each BAT session will be 1-hr in duration. 2x/week and group-based.	Behavioral: Balance, Flexibility, and Tone Exercises; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rey Auditory Verbal Learning Test (RAVLT)	The RAVLT is a valid, reliable, and widely-used instrument of verbal episodic memory and learning, with normative values.	Baseline, 13 weeks, 26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIH TB Cognitive Battery - Flanker Test	A measure of executive functions	Baseline, 13 weeks, 26 weeks
NIH TB Cognitive Battery - Dimensional Change Card Sort Test	A measure of executive functions	Baseline, 13 weeks, 26 weeks
NIH TB Cognitive Battery - Picture Sequence Memory Test	A measure of visual episodic memory	Baseline, 13 weeks, 26 weeks
NIH TB Cognitive Battery - List Sorting Test	A measure of working memory	Baseline, 13 weeks, 26 weeks
NIH TB Cognitive Battery - Pattern Comparison Processing Speed Test	A measure of processing speed	Baseline, 13 weeks, 26 weeks
Everyday Memory Questionnaire	A subjective measure of memory failure in everyday life	Baseline, 13 weeks, 26 weeks
Muscle strength of quads	Muscle strength measure by isokinetic dynamometer	Baseline, 13 weeks, 26 weeks
Peripheral QCT of the tibia	A measure of bone and muscle health	Baseline, 13 weeks, 26 weeks
Blood pressure	Blood pressure - systolic and diastolic	Baseline, 13 weeks, 26 weeks
Lipid panel	Lipid levels	Baseline, 26 weeks
Hemoglobin A1-C	Average blood sugar levels	Baseline, 26 weeks
C-reactive protein	Measure of inflammation	Baseline, 26 weeks
Health resource utilization	Cost of health resource used	Baseline, 13 weeks, 26 weeks
Carotid-femoral pulse wave velocity	Arterial stiffness	Baseline, 13 weeks, 26 weeks
Pittsburgh Sleep Quality Index	Subjective sleep quality	Baseline, 13 weeks, 26 weeks
Actigraph	Using actigraphy data, quantify sleep quality (e.g., duration, efficiency, fragmentation).	Baseline, 13 weeks, 26 weeks
Actigraph	Using actigraphy data, quantify physical activity (e.g., intensity and minutes)	Baseline, 13 weeks, 26 weeks
Actigraph	Using actigraphy data, quantify sedentary behaviour (minutes)	Baseline, 13 weeks, 26 weeks
Fatigue Severity Scale	Subjective fatigue	Baseline, 13 weeks, 26 weeks
PHQ-9	Depression severity	Baseline, 13 weeks, 26 weeks
GAD-7	Generalized anxiety disorder	Baseline, 13 weeks, 26 weeks
Menopause Rating Scale	Menopause symptoms	Baseline, 13 weeks, 26 weeks
EuroQol-5 Domain-5 Level	Quality of life	Baseline, 13 weeks, 26 weeks
International Physical Activity Questionnaire	Physical activity	Every 30 days over 26 weeks
DEXA	Lean mass	Baseline, 13 weeks, 26 weeks
DEXA	Body fat	Baseline, 13 weeks, 26 weeks
DEXA	Appendicular Skeletal Muscle Mass Index (ASMI); a measure of sarcopenia	Baseline, 13 weeks, 26 weeks
Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) Diet score	Diet	Baseline, 13 weeks, 26 weeks
Processing Speed by smartphone	Processing Speed	Baseline, 13 weeks, 26 weeks
Memory by smartphone	Memory	Baseline, 13 weeks, 26 weeks
Productivity Questionnaire	Measure of work productivity	Baseline, 13 weeks, 26 weeks
Brain-Derived Neurotrophic Factor	Neurotrophic Factor	Baseline, 26 weeks
IGF-1	Neurotrophic Factor	Baseline, 26 weeks
Optional Qualitative Interviews	The interviews will involve questions about participants' experiences and impact of perimenopause in their daily lives, their expectations of an exercise intervention, and perceived benefits of group-based exercise training	Baseline, 26 weeks
Optional Measure: Muscle Health	Myosteatosis measured by Upright Open Magnetic Resonance Imaging (UO-MRI) of the mid-thigh and lower leg (dominant)	Baseline, 26 weeks
Optional Measure: Cerebral Oxygenation	Measured by the functional near-infrared spectroscopy (fNIRS)	Baseline, 13 weeks, 26 weeks

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Vancouver Coastal Health Research Institute
• Investigators: Principal Investigator: Teresa Liu-Ambrose, PhD, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2026
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 26, 2025
• First Posted (Actual): December 9, 2025

Study Record Updates

• Last Update Posted (Actual): October 20, 2026
• Last Update Submitted That Met QC Criteria: October 16, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: progressive resistance training, perimenopause
• Additional Relevant MeSH Terms: Mechanical Phenomena; Physical Phenomena; Pliability
• Other Study ID Numbers: H25-01552

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