Biological Sex Differences in the Context of Alzheimer’s Disease: There’s No Time to Sleep on It

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Understanding Alzheimer’s Disease

AD is the most common type of dementia, affecting an estimated 7 million people in Europe alone as of 2025 (European Brain Council). The disease leads to degeneration of nerve cells and neuroinflammation due to accumulation of toxic extracellular amyloid plaques (Aβ), intracellular neurofibrillary tangles, and abnormal activation of microglia. These alterations result in neuronal death, brain tissue damage, and progressive brain atrophy, leading to cognitive decline and other behavioural alterations.

Alzheimer’s is influenced by both modifiable risk factors—such as diabetes, high blood pressure, physical activity, diet, and sleep—and non-modifiable ones like age, genetics, and biological sex.

Sex-Specific Vulnerability: A Research Gap

Women account for nearly two-thirds of AD cases, yet the impact of hormonal changes remains poorly understood (Barth et al., 2023). Major hormonal transitions such as pregnancy and menopause may represent critical windows of vulnerability in developing AD—a topic we discussed extensively with neuroscientist Dr. Claudia Barth.

The Sleep-AD Connection

As Dr. Laura Stankeviciute stated, sleep is not a lifestyle choice but a biological necessity that must be prioritised and protected. Sleep disruption is both a symptom and driver of AD progression, illustrating a two-way interaction between brain degeneration, cognitive decline, and disturbed sleep (Ju et al., 2013; Bubu et al., 2017). These disturbances affect quality of life for patients and caregivers and often hasten patients’ institutionalisation (Petit et al., 2017).

The connection becomes particularly relevant during hormonal transitions related to menopause. During menopause, the number of women reporting sleep problems nearly doubles. Difficulties include falling and staying asleep, frequent awakenings, and daytime fatigue, often intensified by hot flushes and mood disturbances, such as depression (Baker et al., 2019).

Technology and Future Directions

During the interview, we also emphasised incorporating wearable rest-activity pattern measures alongside traditional sleep studies, as sleep unfolds over time, and a single-night polysomnographic recording in the sleep laboratory fails to account for menstrual or seasonal changes. This longitudinal recording is particularly valuable in preclinical AD, as capturing early sleep and circadian disturbances could offer windows for timely, protective interventions.

Co-Creation in Dementia Research

We discussed the vulnerability of caregivers (predominantly women), noting the striking pattern that women are significantly more willing to participate as study volunteers in dementia research, and the importance of engaging participants as partners in science co-creation. As scientists, we are trusted sources of knowledge, but our participants’ insights are invaluable in making science meaningful for all.

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Equality, Diversity and Inclusion (EDI) Glossary

• Co-creation in science: Collaborative research approach involving researchers and communities working together across all research stages to assure relevant, inclusive, and impactful outcomes (Vargas et al., 2022).
• Sex vs. Gender: Sex refers to biological attributes, such as chromosomes, while gender relates to social and cultural roles typically linked to those biological differences.

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Meet the contributors

Dr. Adriana Michalak

Postdoctoral Fellow in Cognitive & Sleep Neuroscience at the Università degli Studi di Modena e Reggio Emilia, Modena, Italy. Chair & Board Representative of Early Career Network (ECN). Vice-Chair of Equality, Diversity and Inclusion Committee (EDIC). 

Links to social media/ websites: LinkedIn, Google Scholar

Speakers

Dr Claudia Barth is a biologist and neuroscientist by training with a strong background in neuroendocrinology. Her work integrates preclinical and clinical perspectives as well as computational approaches to study hormonal transition periods and their impact on brain health and psychiatric disorders. Currently, she is employed as a senior researcher at Diakonhjemmet Hospital (Oslo, Norway), where she leads the FemHealth project. She further serves as Chair of the ENIGMA Neuroendocrinology Working Group – Menopause Subgroup, to foster global research collaborations on this topic. In 2024, she was awarded with an ERC StartingGrant for her project MappingPerimenopause.

Dr Laura Stankeviciute is a clinical neuroscientist working on healthy ageing and the early diagnostics and prevention of Alzheimer’s disease. Her research focuses on how sleep alterations and sex differences, particularly in mid-life, contribute to increased vulnerability to Alzheimer’s. She uses a multi-modal approach combining neuroimaging, fluid biomarkers, cognition and sleep measures. She was recently awarded a grant to lead a wearable-based study mapping longitudinal changes in sleep and circadian metrics and their relationship to Alzheimer’s pathophysiology and cognition. Laura also serves as Program Chair of the Alzheimer’s Association Sleep and Circadian Rhythms Group, where she drives research dissemination, cross-disciplinary collaborations, and public outreach in the field. Laura is also a Scientific Program Chair under the ESRS Early Career Network (ECN).

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Links to Papers

Barth, C., Crestol, A., de Lange, A.-M. G., & Galea, L. A. (2023). Sex steroids and the female brain across the lifespan: Insights into risk of depression and Alzheimer’s disease. The Lancet Diabetes & Endocrinology

Barth, C., Galea, L. A., Jacobs, E. G., Lee, B. H., Westlye, L. T., & de Lange, A.-M. G. (2025). Menopausal hormone therapy and the female brain: Leveraging neuroimaging and Prescription Registry data from the UK biobank cohort. eLife, 13. 

Stankeviciute, L., Tort‐Colet, et al. (2025), Associations between objective sleep metrics and brain structure in cognitively unimpaired adults: Interactions with sex and Alzheimer’s biomarkers. Alzheimer’s & Dementia, 21(6)

 André, C., Stankeviciute, L., Michaelian, J. C., et al. (2025). International Recommendations for Sleep and Circadian Research in Aging and Alzheimer’s Disease: A Delphi Consensus Study.