Research
On this page we post interesting Alzheimer’s research related to menopause and women’s health. We know it can feel like there is no progress in research, this page is here to ensure your optimism.
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Hormone therapy is associated with lower Alzheimer’s disease tau biomarkers in post-menopausal females -evidence from two independent cohorts
Alz Res Therapy 16, 162 (2024). https://doi.org/10.1186/s13195-024-01509-5
These findings suggest that hormone therapy is associated with lower tau pathology in post-menopausal women, which may have implications for reducing Alzheimer's disease risk. It investigates the relationship between hormone therapy (HT) and Alzheimer's disease (AD) biomarkers in post-menopausal women. Key findings include:
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Reduced Tau Pathology with HT: Post-menopausal women undergoing HT exhibited significantly lower levels of tau pathology, as measured by tau-PET standardized uptake value ratios (SUVRs) in various brain regions, compared to those not on HT. Specifically, reductions were observed in Braak regions I-II, III-IV, and V-VI.
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Lower Phosphorylated Tau Levels: HT users also demonstrated significantly reduced concentrations of cerebrospinal fluid (CSF) and plasma phosphorylated tau (p-tau₁₈₁), indicating a systemic decrease in tau pathology.
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Interaction with Amyloid-β (Aβ): The study found that HT interacts with cortical Aβ levels, correlating with lower regional tau accumulation, suggesting a potential modulatory effect of HT on the relationship between Aβ and tau pathology.
Menopause, Brain Anatomy, Cognition and Alzheimer’s Disease
Menopause, Brain Anatomy, Cognition and Alzheimer’s Disease eLife, November 2023. DOI: https://doi.org/10.7554/eLife.91038.1
These findings suggest that while menopausal status and type may not significantly affect cognitive or neuroanatomical measures, the timing of menopause, particularly early or surgical onset, is linked to a higher risk of Alzheimer's disease. The study examines the relationships between menopausal status, type (surgical or natural), age at menopause, and their effects on cognition, brain structure, and Alzheimer's disease (AD) risk. Key findings include:
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Cognitive and Neuroanatomical Measures: The study found no significant impact of menopausal status, type, or age at surgical menopause on brain structure or cognitive performance. However, a positive correlation was observed between age at natural menopause and both brain anatomy and cognition, suggesting that later onset of natural menopause may be associated with better cognitive health.
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Alzheimer’s Disease Risk: Both early and surgical menopause were associated with an increased risk of developing AD, indicating that early or abrupt loss of ovarian hormones may contribute to the development of the disease.
Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia
Front. Aging Neurosci., 23 October 2023. Volume 15 - 2023 | https://doi.org/10.3389/fnagi.2023.1260427
This review examines the relationship between menopause hormone therapy (HT) and Alzheimer's disease (AD) risk. The study analyzes data from both randomized controlled trials (RCTs) and observational studies to assess how different types of HT—estrogen-only therapy (ET) and estrogen-plus-progestogen therapy (EPT)—affect the likelihood of developing AD.
These studies suggested a reduced risk of AD with HT use, with a relative risk of 0.78, indicating a 22% decreased risk. However, observational studies are more susceptible to biases and confounding factors, which may influence these findings. The article highlights a complex relationship between HT and AD risk, with RCTs indicating an increased risk, especially with EPT, and observational studies suggesting a potential protective effect. The authors emphasize the need for personalized approaches when considering HT, taking into account individual risk factors and the type of therapy. They also call for further research to clarify these associations and to explore the underlying mechanisms.
This study discusses research findings on the relationship between the timing of menopause, initiation of hormone therapy (HT), and the risk of Alzheimer's disease (AD). Key findings include:
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Early Menopause and Alzheimer's Risk: Women who experience early menopause (before age 45) have a higher risk of developing AD. This increased risk is associated with a longer duration of estrogen deficiency.
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Timing of Hormone Therapy: Initiating HT more than five years after the onset of menopause may not mitigate the increased risk of AD associated with early menopause. In contrast, starting HT closer to the onset of menopause could be more beneficial in reducing AD risk.
Menopausal hormone therapy and dementia: nationwide, nested case-control study
BMJ 2023; 381 doi: https://doi.org/10.1136/bmj-2022-072770 (Published 28 June 2023)
The study suggests a potential association between MHT, particularly estrogen-progestin combinations, and an increased risk of dementia, even when therapy is initiated around the typical age of menopause onset. It investigates the association between menopausal hormone therapy (MHT) and the risk of developing dementia. Key findings include:
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Increased Risk with MHT Use: The study analyzed data from 5,589 women diagnosed with dementia and 55,890 age-matched controls in Denmark. It found that women who had used estrogen-progestin therapy had a 24% increased rate of developing all-cause dementia compared to those who had never used MHT.
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Duration of Therapy Matters: The risk of dementia increased with longer durations of MHT use. For instance, women who used MHT for one year or less had a 21% increased risk, while those who used it for more than 12 years had a 74% increased risk.
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Age at Initiation: The increased risk was observed even in women who began MHT at age 55 or younger, aligning with current recommendations for MHT initiation.
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Type of Therapy: Both continuous (daily estrogen and progestin) and cyclic (daily estrogen with progestin taken 10-14 days a month) regimens were associated with an increased risk of dementia. However, progestin-only therapy and vaginal estrogen were not linked to an increased risk.
Menopause and Alzheimer’s disease susceptibility: Exploring the potential mechanisms
BMJ 2023; 381 doi: https://doi.org/10.1136/bmj-2022-072770 (Published 28 June 2023)
The review underscores the need for further research to fully understand the mechanisms linking menopause to increased AD risk in women. It examines why women are disproportionately affected by Alzheimer's Disease (AD) and explores menopause as a contributing factor. Key points include:
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Higher Prevalence in Women: AD accounts for 62% of all dementia cases, with a consistently higher prevalence in women, suggesting a gender-specific vulnerability.
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Menopause as a Risk Factor: The review identifies menopause, particularly early onset, as a potential contributor to increased AD risk in women. The hormonal changes during menopause, especially the decline in estrogen, may influence this susceptibility.
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Potential Mechanisms: Several mechanisms are proposed to explain the link between menopause and AD risk:
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Hormonal Shifts: The reduction in estrogen levels during menopause may impact brain function and increase AD risk.
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Gut Dysbiosis: Changes in gut microbiota during menopause could influence neuroinflammation and AD progression.
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Lipid Dysregulation: Alterations in lipid metabolism may affect neuronal health and contribute to AD development.
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Inflammation: Increased systemic inflammation during menopause might exacerbate neurodegenerative processes associated with AD.
This study investigates the impact of menopausal hormone therapy (MHT) on Alzheimer's disease (AD) biomarkers in newly diagnosed menopausal women.
This research provides initial clinical evidence that MHT during menopause can significantly affect AD-related pathophysiological biomarkers, especially in women genetically predisposed to the disease. These findings suggest that MHT may play a role in modulating AD risk factors during menopause.
Does Hormone Replacement Therapy Increase Women's Risk of Dementia?
Neurology. October 25, 2022 issue 99 (17) e1954-e1956 DOI:
The findings suggest that HRT is associated with an increased risk of dementia in women. The study investigates the association between hormone replacement therapy (HRT) and the risk of developing dementia in women. Key findings include:
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Increased Dementia Risk with HRT: The study found that women undergoing HRT have a significantly increased risk of all types of dementia, including Alzheimer's disease, vascular dementia, and other forms.
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Higher Risk with Higher Doses: Higher doses of HRT were associated with a higher risk of developing dementia.
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No Impact of Duration: The duration of hormone use, whether 13.5 years or less versus 13.5 years or more, did not appear to affect the risk.
Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition
Sci Rep 11, 10867 (2021). https://doi.org/10.1038/s41598-021-90084-y
All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. This multi-modality neuroimaging study indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-menopause, peri-menopause, and post-menopause).
These data show that human menopause is a dynamic neurological transition that significantly impacts brain structure, connectivity, and metabolic profile during midlife endocrine aging of the female brain.
Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy
Alzheimer's & Dementia: Translational Research & Clinical Interventions: Volume 7, Issue 1. 13 May 2021 DOI: https://doi.org/10.1002/trc2.12174
This study suggests that menopausal HT, particularly formulations with natural steroids and longer duration of use, is associated with a reduced risk of neurodegenerative diseases. The research investigates the relationship between menopausal hormone therapy (HT) and the risk of developing neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), dementia, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Key findings include:
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Reduced Risk with HT Use: The analysis of 379,352 women aged 45 and older revealed that those who used HT had a significantly reduced risk of developing NDDs compared to non-users. Specifically, HT users exhibited a 58% reduction in the risk of combined NDDs.
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Impact of HT Formulations: Natural steroid formulations containing 17β-estradiol and/or progesterone were associated with a greater reduction in NDD risk compared to synthetic formulations. Oral HT users showed a significant risk reduction for combined NDDs, while transdermal HT users had a notable decrease in risk for all-cause dementia and MS.
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Duration of Therapy: Long-term HT use (over one year) was linked to a greater protective effect against NDDs, AD, PD, and dementia compared to short-term use (one year or less).
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Age-Related Effects: The protective effects of HT became more apparent in women aged 65 and older, indicating that age may influence the efficacy of HT in reducing NDD risk.
Sex-driven modifiers of Alzheimer risk: A multimodality brain imaging study
Neurology. July 14, 2020 issue. 95 (2) e166-e178 DOI:
The study highlights that middle-aged women exhibit a higher burden of AD-related brain biomarkers compared to men, potentially due to menopause and hormonal changes. It investigates sex differences in Alzheimer's disease (AD) risk by analyzing various brain biomarkers in cognitively normal individuals aged 40 to 65. Key findings include:
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Higher AD Biomarker Levels in Women: The study found that women exhibited higher levels of β-amyloid deposition, reduced glucose metabolism, and decreased gray and white matter volumes compared to men. These biomarkers are associated with increased AD risk.
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Influence of Menopause and Hormonal Factors: Menopause and related hormonal changes were identified as significant factors contributing to the observed sex differences in AD biomarkers. This suggests that hormonal transitions may play a role in increasing AD risk among women.
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Independence from Other Risk Factors: The observed differences remained significant even after adjusting for various factors such as age, education, APOE status, family history, and lifestyle factors, indicating a robust association between sex, hormonal changes, and AD biomarkers.
Sex and Gender Driven Modifiers of Alzheimer’s: The Role for Estrogenic Control Across Age, Race, Medical, and Lifestyle Risks
Front. Aging Neurosci., 15 November 2019
Sec. Alzheimer's Disease and Related Dementias
Volume 11 - 2019 | https://doi.org/10.3389/fnagi.2019.00315
Research indicates that after advanced age, the major risk factor for late-onset Alzheimer’s disease (AD) is female sex. Out of every three AD patients, two are females with postmenopausal women contributing to over 60% of all those affected. Sex- and gender-related differences in AD have been widely researched and several emerging lines of evidence point to different vulnerabilities that contribute to dementia risk. Among those being considered, it is becoming widely accepted that gonadal steroids contribute to the gender disparity in AD.
This review discusses genetic, medical, societal, and lifestyle risk factors known to increase AD risk differently between the genders, with a focus on the role of hormonal changes, particularly declines in 17β-estradiol during the menopause transition (MT) as key underlying mechanisms.
Two thirds of all persons with late-onset Alzheimer’s disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer’s disease (AD) biomarker changes [brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18FFDG PET and structural MRI] and cognitive performance in midlife.
This article underscores the critical need for heightened awareness and proactive strategies to mitigate menopause-related Alzheimer's risk in women. It explores the connection between menopause and the increased risk of Alzheimer's disease (AD) in women. Key points include:
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Increased Risk in Women: Women constitute approximately two-thirds of Alzheimer's patients globally, a disparity not solely attributable to longer lifespans. Menopause-related hormonal changes, particularly the decline in estrogen, are believed to contribute to this heightened risk.
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Menopause as a Neurological Transition: Menopause involves neurological symptoms such as disruptions in thermoregulation, sleep, and cognitive functions. Brain imaging studies have identified an "Alzheimer's endophenotype" in perimenopausal and postmenopausal women, characterized by reduced brain metabolism, loss of gray and white matter, and increased amyloid-beta deposition—a hallmark of Alzheimer's pathology.
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Bioenergetic Crisis: During menopause, the female brain experiences a bioenergetic crisis due to the loss of estrogen's regulatory effects on glucose metabolism. This leads to increased reliance on ketone bodies for energy, potentially resulting in white matter degradation and mitochondrial dysfunction, thereby elevating the risk of cognitive decline and Alzheimer's disease.
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Early Intervention: The authors advocate for early therapeutic interventions targeting women in their 40s, prior to the onset of neurological symptoms.
Understanding the impact of sex and gender in Alzheimer's disease: A call to action
Alzheimers Dement. 2018 Jun 12;14(9):1171–1183. doi: 10.1016/j.jalz.2018.04.008
This paper emphasizes the critical need to consider sex and gender differences in Alzheimer's disease (AD) research and treatment. Key findings include:
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Prevalence: Approximately two-thirds of individuals diagnosed with AD are women.
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Research Gaps: Historically, sex and gender differences have been underexplored in AD studies, hindering progress in understanding and treating the disease effectively.
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Priority Areas for Research: The authors identify 12 key areas requiring further investigation, including:
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Sex-specific risk factors such as menopause and hormone therapy.
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Genetic risk variations between sexes.
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Differences in disease progression and biomarker trajectories.
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Impact of sex and gender in diverse racial and ethnic groups.
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Influence of caregiving roles on AD risk.
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This study reviews most relevant/new information about estrogen in relation to cognitive decline/aging. Individual results were inconsistent but a wider look at overall data indicates that estrogen plays a key part in the progression of Alzheimer's Disease. Further research needs to look into hormone supplementation's possible crucial windows in large groups of younger people. Their cognitive outcomes need to be tracked for an extended period of time (this would help shed light on effective intervention and treatment before pathological feature of AD have begun).
The findings suggest a critical window near menopause when HT may provide neuroprotective benefits. The study investigates the impact of hormone therapy (HT) on Alzheimer’s disease (AD) risk, with a focus on the timing, duration, and type of HT used in postmenopausal women. Key findings include:
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Women who began hormone therapy within five years of menopause experienced a 30% reduced risk of Alzheimer’s disease.
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Longer durations of HT (10 years or more) further enhanced this protective effect.
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Starting HT five or more years after menopause showed no significant association with a reduced risk of AD.
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Women who recently started estrogen-progestin therapy ("opposed" HT) near the study's baseline exhibited an increased risk of Alzheimer’s disease.