Women and Alzheimer's disease risk: a focus on gender

A previous chapter highlighted the biological mechanisms by which female sex contributes to Alzheimer's disease (AD) risk and outcomes. However, discussion of AD in women is incomplete without considering the impact of female gender on AD risk, as gender encompasses psychosocial and cultural differences between women and men that also modulate risk for cognitive decline. The current chapter discusses several main social determinants of health and explains how women, as a historically oppressed population, may be particularly vulnerable to the effect of each on cognition. This chapter also considers the disproportionate female burden of dementia caregiving, how associated stresses augment risk for later cognitive decline among caregivers themselves, and how the COVID-19 pandemic may add to this risk. Understanding the gender-specific factors that affect AD risk and disease progression is essential for developing targeted preventative interventions and treatments. Future research is necessary to better characterize how social determinants of health uniquely impact female cognition compared to males. Moreover, future studies focused on gender identities outside of the male–female binary are critical to developing a holistic understanding of how gender may impact late-life cognition. © 2023 Elsevier Inc. All rights reserved.

Women and Alzheimer's disease

Approximately, two-thirds of individuals with Alzheimer's disease (AD) are women. Though previously attributed to differences in lifespan, accumulating evidence suggests that the reasons for the higher prevalence of AD in women are multifactorial and related to differences in risk factors, biomarkers, and neuropathology. Sex also contributes to significant disease heterogeneity, which has important implications for prevention and treatment. This chapter discusses the evidence for sex differences in AD, with an emphasis on disease presentation, biomarkers, pathophysiology, progression, and risk. Women tend to present later in the disease course and with different clinical features, progress faster, and are disproportionately affected by the APOE-ϵ4 risk allele and AD neuropathologic changes. Lifetime estrogen exposure, pregnancy, and menopause also affect a woman's risk for cognitive decline later in life. Despite such differences, women are dramatically underrepresented in pharmacologic randomized control trials, leading to significant gaps in knowledge regarding the most effect AD treatment strategies for women. Both researchers and providers need to be aware of sex differences in AD risk, presentation, and outcomes to develop sex-specific prevention and treatment strategies, as well as provide optimum healthcare to women as they age. © 2023 Elsevier Inc. All rights reserved.

HIGH NEUTRALIZING CONVALESCENT PLASMA RESULTS in RAPID CLEARANCE of SARS-CoV-2

Background: Neutralizing antibodies are recognized as a principal correlate for protection induced by SARS-CoV-2 vaccines and have been considered for antiviral treatment as an active component in convalescent plasma therapy (CPT) and as monoclonal antibody therapeutics. However, unless used at a very early stage of infection, antibody-based SARS-CoV-2 therapies have not achieved the substantial disease-modulating effect hoped for. Methods: Here, we conducted a proof-of-principle study of CPT based on a phase I trial in thirty hospitalized COVID-19 patients with a median interval between the onset of symptoms and the first transfusion of 9 days (IQR, 7-11.8 days). A comprehensive longitudinal monitoring of the virologic, serologic, and disease status of recipients in conjunction with detailed post-hoc seroprofiling of transfused convalescent plasma allowed deciphering of parameters on which plasma therapy efficacy depends. Results: In this study, CPT was safe as evidenced by the absence of transfusion-related adverse events. We also observed an overall low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (p = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio (HR) = 3.0 [95% confidence interval (CI) 1.1;8.1], p = 0.026) (Figure 1). Endogenous immunity had strong effects on virus control. Lack of endogenous neutralizing activity at baseline was associated with a higher risk of systemic viremia. The onset of endogenous neutralization had a noticeable effect on viral clearance but, importantly, even after adjusting for their endogenous neutralization status recipients benefitted from plasma therapy with high neutralizing antibodies (HR= 4.0 [95% CI 1.3;13], p = 0.017). Conclusion: In summary, our data demonstrate a clear impact of neutralizing antibody therapeutics on the rapid clearance of viremia and with this provide directions for improved efficacy evaluation of current and future SARS-CoV-2 therapies beyond antibody-based interventions. In particular, incorporating an assessment of the endogenous immune response and its dynamic interplay with viral production is critical for determining therapeutic effect.