Health, Imaging, and Cognition Across the Menopausal Transition

NCT07021664 | Not Yet Recruiting

• 1 other identifier: 2025-58-28
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This observational cross-sectional study aims to better understand how the menopausal transition affects brain energy metabolism and cognition. Menopause, a natural stage in a woman's life, is typically divided into three phases: premenopause, perimenopause, and postmenopause. This transition involves hormonal fluctuations and a decline in estrogen levels, which can impact physical, emotional, and cognitive well-being. Common symptoms include hot flashes, sleep disturbances, mood changes, and difficulties with memory and concentration. Emerging evidence suggests that the decline in estrogen may impair how the brain uses glucose, its primary energy source. This reduction in glucose metabolism is thought to contribute to cognitive difficulties reported during midlife. In contrast, the brain's capacity to use ketones-alternative energy substrates produced during fasting or low-carbohydrate intake-appears preserved during aging and hormonal changes. Increasing circulating ketones may offer a promising strategy to support brain energy and cognitive function. To explore these relationships, the study will employ advanced brain imaging (PET scans) to assess glucose and ketone uptake in the brain. Additional measures will include hormone levels, cognitive testing, continuous glucose monitoring, and MRI. PET tracers will also be used to evaluate estrogen receptor distribution, providing insight into how the brain responds to hormonal changes. A total of 45 women aged 35-60 will be enrolled and categorized into three groups (15 per group): premenopause, perimenopause, and postmenopause. Each participant will attend four study visits that include questionnaires, blood tests, cognitive assessments, metabolic measurements, and imaging procedures. The results may help identify early neurobiological and metabolic markers associated with the menopausal transition. These findings could inform new approaches to preserve brain health and prevent cognitive decline in aging women. Improving understanding of how the female brain adapts to hormonal shifts may ultimately support more targeted strategies for promoting healthy aging.

Conditions

Menopause

Keywords

menopause; cognition; metabolism; estrogen; ketone; PET scan; estrogen receptor

Outcome Measures

Primary Outcomes (2)

• cerebral metabolic rates (μmol/100 g/min) measured by PET (11C-AcAc +18F-FDG)

  Brain energy metabolism will be quantified using two PET tracers: 11C-acetoacetate (for ketone use) and 18F-fluorodeoxyglucose (for glucose use). This will allow comparison of brain fuel usage between three menopausal groups (PRE, PERI, POST).Total Cerebral metabolic rates (μmol/100 g/min) (CMR tot= CMR acac + CMRglu)

  1 day at baseline

• Tracer influx rates (k) measured by PET (11C-AcAc +18F-FDG)

  Brain energy metabolism will be quantified using two PET tracers: 11C-acetoacetate (for ketone use) and 18F-fluorodeoxyglucose (for glucose use). This will allow comparison of brain fuel usage between three menopausal groups (PRE, PERI, POST). tracer influx rates (K values).

  1 day at baseline

Secondary Outcomes (5)

• Time-activity curves of the estrogen receptor in the brain (by 18F-4FMFES PET)

  1 day at baseline

• distribution volume ratio of the estrogen receptor in the brain (by 18F-4FMFES PET)

  1 day at baseline

• Glucose variability (SD of glucose measured by continuous glucose monitoring)

  Over 5 days following sensor placement et stabilisation

• Glucose average (mean of glucose measured by continuous glucose monitoring)

  Over 5 days following sensor placement et stabilisation

• Time in range

  Over 5 days following sensor placement et stabilisation

Other Outcomes (22)

• Brain volume

  1 day at baseline

• Rey Auditory Verbal Learning Test (RAVLT)

  1 day at baseline

• Stroop Color and Word test (Stroop Test) (secondes)

  1 day at baseline

Study Arms (3)

premenopause

Women between 35 and 55 years old who still have regular menstrual cycles, with no noticeable changes in the past 10 months.

perimenopause

Women between 40 and 60 years old who have experienced changes in their menstrual cycles, such as irregular timing (varying by more than 7 days) for at least 10 cycles, or no period for 3 to 11 months.

postmenopause

Women between 45 and 65 years old who have not had a menstrual period for 12 months or more.

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy individuals from the general population

You may qualify if:

• Able to read and speak French
• Perimenopause: Women aged 40 to 60; Menstrual cycles varying by more than 7 days per cycle for at least 10 cycles, or no period for 3 to 11 months
• postmenopause: Women aged 45 to 65; No menstrual period for ≥ 12 months

You may not qualify if:

• Pregnancy, childbirth within the past 12 months, or breastfeeding
• Use of hormone replacement therapy or hormonal contraceptives in the past 6 months
• contraindications to MRI (e.g., presence of non-compatible metallic objects)
• Claustrophobia
• Type 1 diabetes
• Adherence to a ketogenic intervention (e.g., ketone supplements, intermittent fasting, ketogenic diet) in the past 3 months
• Engaging in intense physical activity 5 times per week or more
• Any significant neurological disorder (e.g., dementia, brain tumor, seizure disorder, history of significant head trauma with persistent neurological deficits, known structural brain abnormalities)
• History of oophorectomy or hysterectomy
• Any significant psychiatric disorder (e.g., major depression within the past 2 years, bipolar disorder, schizophrenia)
• Systemic diseases or unstable/uncontrolled medical conditions (e.g., cardiovascular disease, uncontrolled diabetes, kidney or liver disorders)
• Any other condition that may interfere with participation, as judged by the study physician

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Nestlé Health Science: collaborator

Study Sites (1)

Centre de recherche sur le Vieillissement

Sherbrooke, Quebec, J1H 4C4, Canada

Location

Related Publications (17)

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• Paquette M, Phoenix S, Lavallee E, Rousseau JA, Guerin B, Turcotte EE, Lecomte R. Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using 18F-FES and 18F-4FMFES PET Imaging. Mol Imaging Biol. 2020 Oct;22(5):1403-1413. doi: 10.1007/s11307-020-01520-w. Epub 2020 Jul 22.

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• Arjmand S, Bender D, Jakobsen S, Wegener G, Landau AM. Peering into the Brain's Estrogen Receptors: PET Tracers for Visualization of Nuclear and Extranuclear Estrogen Receptors in Brain Disorders. Biomolecules. 2023 Sep 18;13(9):1405. doi: 10.3390/biom13091405.

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• Fortier M, Castellano CA, St-Pierre V, Myette-Cote E, Langlois F, Roy M, Morin MC, Bocti C, Fulop T, Godin JP, Delannoy C, Cuenoud B, Cunnane SC. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimers Dement. 2021 Mar;17(3):543-552. doi: 10.1002/alz.12206. Epub 2020 Oct 26.

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• Croteau E, Castellano CA, Richard MA, Fortier M, Nugent S, Lepage M, Duchesne S, Whittingstall K, Turcotte EE, Bocti C, Fulop T, Cunnane SC. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease. J Alzheimers Dis. 2018;64(2):551-561. doi: 10.3233/JAD-180202.

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• Mosconi L, Brinton RD. How would we combat menopause as an Alzheimer's risk factor? Expert Rev Neurother. 2018 Sep;18(9):689-691. doi: 10.1080/14737175.2018.1510320. Epub 2018 Aug 13. No abstract available.

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• Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Osorio RS, Connaughty C, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Swerdlow RH, Brinton RD. Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery. PLoS One. 2017 Oct 10;12(10):e0185926. doi: 10.1371/journal.pone.0185926. eCollection 2017.

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  PMID: 30540774 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood and plasma will be retained

MeSH Terms

Conditions

Ketosis

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Stephen Cunnane, Ph.D

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melanie Fortier, M.Sc.

CONTACT

1-819-821-5206; recherche.cerveau@usherbrooke.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2025
• First Posted: June 15, 2025
• Study Start: July 1, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: June 15, 2025

Record last verified: 2025-05

Locations

CA (1)