Addressing Modifiable Risk Factors of Alzheimer Disease Is Effective for All and Has Greater Impact in Women 

In the CEDAR study (NCT03687710), clinical interventions designed to reduce risk factors for Alzheimer disease (AD) improved cognition for both individuals with and without cognitive impairment at baseline. Further analysis of data from the study, published in the Journal of the Prevention of Alzheimer’s Disease, shows these interventions had a greater impact on specific risk factors among women. 

Richard Isaacson, MD, director, Alzheimer's Prevention Clinic, Schmidt College of Medicine, Florida Atlantic University and principal investigator for CEDAR said, "Women are more likely than men to develop AD, not just because they live longer, but also because of biologic and social differences, including hormonal changes during the perimenopause transition, sex-specific impact of high abdominal adiposity, and biopsychosocial risk factors, such as sex-specific life stressors like widowhood and more. While adherence to individualized preventive care recommendations improved cognitive outcomes in both women and men, cardiovascular and dementia risk factors improved more so in women, who are known to have a higher risk of AD." 

Among participants without cognitive impairment (including some with preclinical AD), there were larger improvements for women on the Multi-Ethnic Study of Atherosclerosis (MESA) risk score. For those with mild cognitive impairment (MCI) or early AD, women had higher risk score reductions on both the MESA and Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) scales. Women in the study also had greater reductions of blood glucose, low-density lipoprotein (LDL) cholesterol, and the prediabetes blood biomarker HbA1C. 

Dr. Isaacson continued, "We need more people working on modifiable risk factors for AD prevention. Our initial 2-site study planned to include 280 participants, but due to Hurricane Maria, our collaborating site in San Juan, Puerto Rico was unable to continue operations and 106 subjects were lost to follow-up. Our next aims to enroll 480 people at 9 multinational sites working as a consortium with harmonized measures and methods. We hope to move the field of AD prevention forward, and in the meantime, encourage patients and their clinicians to “know their numbers.” That is, be aware of individual risk factors, and work together to track and change behavior if those move in a direction that increases the risk of AD."  

In this study, individualized risk-reduction interventions included education/genetic counseling, pharmacologic and nonpharmacologic approaches (eg, medications, supplements, exercise and diet counseling, vascular risk reduction, sleep hygiene, stress reduction, and general medical care), and other evidence-based interventions. The individualization of interventions was based on baseline clinical assessments, including detailed clinical history, physical examination, anthropometrics, blood biomarkers, apolipoprotein-ε4 (APOE-e4) genotyping, and cognitive assessment. 

Although all participants were asked to share their sex assigned at birth and their self-identified gender, the number of transgender and nonbinary individuals was too small to make any valid comparisons. Nonbinary and transgender individuals were included in the analysis based on their sex assigned at birth.