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Lipedema, a poorly understood disease characterized by irregular fat distribution and accumulation, can dramatically impact quality of life, workforce participation, and healthcare costs. It frequently causes physical discomfort, psychological distress, and other health complications. Yet despite Lipedema’s impacts and a high estimated prevalence of the disease, we know little about how frequently it manifests in different populations, how regularly symptoms disrupt daily life, or its precise healthcare costs.

This knowledge gap is largely due to inadequate studies of epidemiology (i.e., patterns in the distribution of a disease). Accurate and innovative prevalence data is necessary to understand the true dimensions and impacts of Lipedema. With more accurate prevalence data, we can identify important research questions, develop better diagnostics and treatments, educate patients and providers—and crucially, we can motivate funders and policymakers to prioritize all of these efforts. In this post, we review the status of current epidemiology research and spotlight how high-quality studies and new research approaches could reveal Lipedema’s true burden to both individuals and healthcare systems.

The Need for Precise Lipedema Prevalence Data

While we know Lipedema occurs almost exclusively in women, Lipedema’s precise prevalence is uncertain. A literature review published in 2020 estimated that 10-11% of women—some 400 million people—have Lipedema [1]. But numbers vary widely across different studies and tend to be based primarily on European populations, which likely skews the overall picture. One British dermatology department documented 67 Lipedema cases in 15 years, resulting in a minimum prevalence estimate of 0.001%— although the authors noted this is likely an underestimate [2]. A Brazil-based online screening tool indicated that 12.3% of respondents would meet criteria for Lipedema [3], whereas one screening in Germany found 4.8-9.7% of participants had moderate to pronounced Lipedema [4].

Prevalence of Lipedema Symptoms

In addition to identifying Lipedema’s prevalence, we also need to better understand the prevalence of specific symptoms in the disease. For example, all published Lipedema diagnosis guidelines mention the presence of pain as a possible symptom. Yet recent estimates of pain and sensitivity prevalence range between 62% and 100% [2,5,6,7,8,9,10,11,12,13,14]. (Because some research studies require pain, the frequency of 100% could be an artifact of the inclusion criteria necessary to be enrolled in the study.) Moreover, people with Lipedema report pain that can range from mild to debilitating and that can range in quality from “dull” to “throbbing” to “tearing”—yet many studies do not describe pain intensity or quality at all.

These challenges extend to a range of other symptoms. In addition to the hallmark excess adiposity in limbs, some people with Lipedema report daily fatigue [15,16] attention and working memory issues (commonly referred to as “brain fog”), easy bruising, swelling, cold skin, spider veins, fat pads around the knees, and hypermobile joints. However, these reports tend to draw on a variety of small studies that may use different approaches to symptom measurement. Without robust data from systematic, large-scale surveys, the true prevalence of these symptoms remains unclear, and it is difficult to identify the most urgently needed treatments.

Beyond Lipedema: A Web of Comorbidities

Although Lipedema may be mistaken for other health conditions, people with Lipedema may also have other conditions. One study found that Lipedema patients are more likely to develop obesity, lymphedema, migraines, and hypothyroidism, but these findings require further confirmation [10]. Similar to prevalence estimates for Lipedema itself, prevalence estimates for these comorbidities vary dramatically. Obesity may affect between 37.6% and 79.6% of Lipedema patients [10, 14, 17, 18], and migraines impact anywhere from 7% to 22.6% of patients [10, 14, 17, 19, 20]. If we knew how often these comorbidities overlap with Lipedema, clinicians could build better care plans and researchers could better quantify the disease’s economic toll.

The Hidden Cost to Healthcare Systems

Lipedema burdens not only individuals, but entire healthcare systems. The precise economic burden of Lipedema is largely hidden due to incomplete prevalence data. How much money do Lipedema patients spend on healthcare? How frequently does Lipedema force people out of the workforce? Establishing a clear picture of these costs will enable us to build accurate value frameworks that can assess the cost-effectiveness of specific therapies.

Understanding Lipedema Prevalence: Obstacles and Opportunities

Despite the urgent need for accurate data on Lipedema prevalence, there are still substantial challenges to collecting this information. High-quality epidemiology studies require significant financial resources and time. We can’t simply identify people who have been diagnosed with Lipedema, because a lack of standardized diagnostic criteria and diagnostic coding makes these data unreliable. Instead, we may need more innovative approaches to prevalence studies.

Novel data collection practices could help. Large public health databases are one potential tool. For example, the UK Biobank, the Germany-based National Cohort study (NAKO), and the U.S.-based National Health and Nutrition Examination Study (NHANES), may have relevant data on large numbers of people. Similarly, we could collect data through collaborations with specific healthcare providers who are more likely to engage with Lipedema patients (such as gynecologists or bariatric surgeons), or by partnering with long-term studies of other conditions (such as obesity) to track risk of Lipedema in those populations.

In fact, this kind of data mining has already proven fruitful. In November 2022, an analysis of data from the UK Biobank identified women with and without the Lipedema phenotype [21]. The researchers subsequently used that information to identify 18 regions within the genome that likely play a role in Lipedema. This analysis demonstrates how, despite challenges, we can leverage innovative approaches and existing resources to further our knowledge of this disease's prevalence and mechanisms.

Collective Efforts to Improve Outcomes

As challenging as it may be, epidemiology studies have the potential to change the foundations of Lipedema research and care. With more precise prevalence estimates, we can demonstrate to funders and policy makers the importance of Lipedema research and public health approaches and broaden support for a wide range of innovative future research.

So what creative ideas do you have to uncover the true prevalence of Lipedema? What strategies have been successful in other fields that have faced similar challenges? We want to hear what you think! Your input may lead us to new and effective ways of understanding the prevalence of Lipedema and help us improve the lives of everyone affected by this disease.

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As dementia continues to impact millions of people worldwide, researchers and policymakers have urgently sought effective treatments to prevent and treat the disease. One promising area of research is the potential for existing medications for chronic conditions to reduce the risk of dementia or slow its onset. Researchers at USC’s Schaeffer Center for Health Policy and Economics have been at the forefront of these investigations.

A growing body of research highlights existing blood pressure medications as one potential avenue for reducing dementia risk. Currently, nearly half of adults in the U.S. have high blood pressure, most of whom are prescribed blood pressure medication (called antihypertensives). Antihypertensives may reduce dementia risk directly by lowering blood pressure, a risk factor for cardiovascular disease, stroke and subsequent dementia. Some antihypertensives have also been found to impact Alzheimer's disease pathology and provide further protection against this common form of dementia. (add citation). Clinical trials have not given us a definitive answer on the relationship between blood pressure medications and dementia. USC Schaeffer Center researchers have turned to real-world data to probe the relationship between antihypertensive use and dementia risk in the U.S. population and among minoritized populations who are at the highest dementia risk of dementia.

Beyond Blood Pressure: Antihypertensive Drug Class and Dementia Protection

A 2018 study led by Douglas Barthold, Geoffrey Joyce and Julie Zissimopoulos used examined longitudinal data on the use of antihypertensive medications and new dementia diagnoses of millions of Medicare beneficiaries. With multiple different classes of antihypertensive medications used to treat hypertension, the authors focused on distinguishing between them. The study reported that high blood pressure treatments that act on the renin-angiotensin hormone system reduced the risk of dementia more than antihypertensives that do not act on this system. Importantly, the study provided insight into heterogeneity in effects for men and women and for different racial and ethnic persons. RASRenin-angiotensin-acting antihypertensives were associated with reduced risk of dementia in white men and white and Black women, but not in Hispanic men and women.

Many older individuals with hypertension also have other chronic conditions treated with pharmaceuticals. A second study conducted by the same team in 2020 found that the use of renin-angiotensin-related blood pressure drugs along with certain cholesterol-lowering drugs (pravastatin or rosuvastatin) was associated with reduced risk of developing dementia more than any other combination of cholesterol and antihypertensive medicines.

Two recent studies also reported heterogeneity in response to different classes of hypertensive medications. One, an RCT randomized clinical trial from researchers at Uppsala University and the University of New South Wales, found considerable variation in individuals’ blood pressure response to four different classes of antihypertensives, including two that act on the renin-angiotensin system and two that do not. A recent study from researchers at the University of Washington reported results similar to early studies by the USC team. Study authors Zachary Marcum and colleagues found that antihypertensives that stimulate type 2 and 4 angiotensin II receptors were associated with lower risk of developing dementia compared to medications that inhibit those receptors.

The Path Forward

Antihypertensives may provide a low-cost and scalable opportunity to reduce dementia incidence worldwide. However, the considerable variation in individuals’ response to these medications points to potential benefits to personalized therapy. Pragmatic trials may offer a strategy for measuring the complex relationships between medication class, sex, race and ethnicity for informing on effective treatment and prevention strategies for dementia.

The Apolipoprotein E gene (APOE) has emerged as a central player in the pathogenesis of Alzheimer’s disease (AD), with distinct APOE isoforms exerting diverse effects on AD pathogenesis. Accumulating evidence suggests that APOE influences not only amyloid-beta and tau pathologies, but also neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. However, the underrepresentation of diverse populations in AD and APOE research remains a key issue. To conduct a thorough review of the state of the science on APOE and AD and to foster the development of transformative neuroscience research, the Alzheimer’s Association convened a multidisciplinary group of researchers at the AAIC Advancements: APOE workshop on March 6-7, 2023. Participants developed a comprehensive overview of the APOE gene, its isoforms, and their roles in AD pathogenesis, including the influence of APOE genotype on pathological pathways and disease progression. This manuscript presents the results of the workshop and outlines the most significant avenues for future APOE and AD research, drawing on recent progress in APOE-targeted therapeutic strategies, updates on disease models, and various interventions that modulate APOE function and expression. Understanding APOE’s multifaceted roles in AD pathogenesis and developing targeted interventions will help advance precision medicine and aid in the prevention and treatment of AD (Leng and Edison, 2021).