Dementia is more prevalent in females than in males. In the United States, women account for nearly two-thirds of Alzheimer’s disease, the most common form of dementia. Previously, researchers suggested this discrepancy may be due to women living longer, with increasing age being the strongest known risk factor for dementia.
However, growing evidence suggests that sex differences may influence both the development and progression of dementia. Notably, hormonal changes, genetics, healthcare disparities, and social determinants of health could all contribute to the unequal burden of dementia among women. Additionally, women may respond differently to certain risk factors across their life span.
Now, a new study from researchers at the University of California, San Diego School of Medicine suggests that women may experience stronger cognitive effects from several modifiable dementia risk factors than men, even when those risks are less common overall.
Published in Biology of Sex Differences, the findings support tailored dementia prevention strategies that target the specific modifiable risk factors most applicable to each individual.
In the study, the researchers analyzed health and cognitive data from more than 17,000 middle-aged and older adults in the U.S.
They examined 13 established modifiable dementia risk factors using data from the nationally representative Health and Retirement Study. These included depression, obesity, physical inactivity, smoking, hearing loss, diabetes, hypertension, sleep problems, alcohol use, cholesterol levels, poor vision, social isolation, and education level.
The analysis found notable differences in both the prevalence and impact of these factors between sexes.
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Namely, females were more likely to report depression, physical inactivity, sleep problems, elevated cholesterol, smoking, poor vision, and lower educational attainment. Meanwhile, males were more likely to experience hearing loss, diabetes, and heavy alcohol use.
However, the most significant finding was that several risk factors appeared to be more strongly associated with poorer cognitive performance in females.
Conditions relating to cardiovascular and metabolic health, such as hypertension and higher body mass index (BMI), had stronger negative cognitive associations in women than in men. Additionally, although hearing loss and diabetes were more common in males, they were linked to worse cognitive outcomes in females.
These findings suggest that the higher dementia risk in females may reflect both greater exposure and stronger negative effects of these risk factors.
Judy Pa, PhD, professor of neurosciences at UC San Diego School of Medicine and corresponding author of the study, spoke to Medical News Today about the possible sex-based differences that may cause these factors to affect female cognition more strongly:
“There are a few areas of research that link women and heightened Alzheimer’s disease risk. In addition to the additional stressors from caregiving (and sandwich generation of young children plus aging parents), strong evidence shows that the major genetic risk factor for late-onset Alzheimer’s disease is the APOE4 risk allele.”
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“This is found in about 25% of the general population and elevates the risk of developing Alzheimer’s disease dementia in women more than in men. This may be due to the role of the APOE gene in lipid metabolism (heart health),” she continued.
“Another factor to consider for women is the major life event of menopause, which is largely a neurological [transition]. There are major biological shifts that occur with menopause, like changes in blood pressure, glucose metabolism, and inflammation. But we don’t understand how these systemic changes influence brain health.”
— Judy Pa, PhD
Pa also mentions they are part of a national scientific leadership team that is studying how menopause influences brain health through the Longitudinal Menopause Project (LMP). She adds that this study will serve as one of the flagship scientific programs examining the perimenopause period in women 35 to 59 years of age.
“We would encourage anyone to do as much as they can to live a healthy and active lifestyle. The adage in our field is, ‘if it’s good for the heart, it’s good for the brain.’”
“This means regularly visiting your doctor who can help monitor and treat conditions like hypertension, managing vision and hearing problems, living a physically active lifestyle including weight-bearing exercises especially for women, and eating a heart- and brain-healthy diet.”
“There is no single magic bullet but rather embracing a healthy lifestyle. Keeping your body healthy will keep your brain healthy.”
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— Judy Pa, PhD
The researchers suggest the results support a more personalized approach to dementia prevention, often referred to as precision medicine.
Rather than applying the same prevention priorities to everyone, future strategies could move beyond identifying the most widespread risks and instead focus on the risk factors that appear most harmful within specific groups.
“We are pursuing different approaches to personalized dementia prevention, including a current large NIH clinical trial grant under review,” Pa told MNT.
“The key is personalized, precision prevention. What is the best treatment and for whom? This includes both sex/gender and genetic risk as there is emerging evidence that dementia prevention approaches could differ depending on APOE4 status,” she said.
“While this newly published study is not causal in nature as it comes from longitudinal observation data in the U.S., we are examining each of the factors individually based on one’s risk profile to better understand causality in a randomized clinical trial, and one factor of many is sex/gender.”
— Judy Pa, PhD
Based on these findings, for females this may include a greater emphasis on treating depression, increasing physical activity, managing blood pressure, improving cardiovascular health, and addressing obesity and metabolic conditions.
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As these risk factors are modifiable, they offer practical opportunities to reduce dementia risk before cognitive symptoms appear.
“Women face additional factors in their lives that contribute to later-life brain health. This includes stress from caregiving, as 2/3 of dementia caregivers are women.”
“Women also uniquely experience biological shifts during menopause that can cause temporary cognitive symptoms, impaired sleep quality, and overall lower quality of life.”
“Recognizing these additional factors that impact women can empower women to seek answers and appropriate treatment or lifestyle modifications to manage these events in midlife. Protecting midlife health is important for protecting the brain in the long-term as we get older.”
However, the study authors add that additional long-term research is still necessary to better understand why these sex-based differences emerge and how they evolve over time.
“We are deeply committed to tailored, personalized, precision prevention approaches for dementia,” Pa emphasized to MNT.
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“We believe a one size fits all approach will not work for everyone. And that we are likely to have greater benefit and impact if approaches are tailored to a specific risk factor profile, including sex/gender, APOE4, and current risks like untreated high blood pressure, inactive lifestyle, poor sleep, and early cognitive complaints, among others.”
— Judy Pa, PhD
“With successful NIH funding, we will launch a precision prevention approach in a large, randomized controlled trial of approximately 1,000 older adults in the U.S., to move the needle closer and closer to tailored prevention strategies for our communities,” Pa announced.
Although more research is required to develop more targeted interventions for disproportionately affected groups, such as females, previous research has highlighted various risk factors for the general public.
Namely, evidence suggests that nearly half of all dementia cases worldwide can be prevented or delayed by addressing 14 modifiable risk factors across a person’s lifespan. These include:
As such, while the magnitude of certain risk factors will vary among individuals, it is generally advisable to address preexisting health issues, adopt a healthier dietary plan, increase physical activity, and maintain cognitive stimulation to help prevent dementia.
