Jessica Caldwell, PhD

"That kind of precision medicine, including directing medical targets toward women and men specifically, is certainly the goal. I don't think we're there yet, but I think that work like mine points to the fact that it may be more important to engage women, either in trials or in preventative approaches, even earlier than men.”

, a recently conducted study explored sex differences in regions of the default network (DN), otherwise considered one of the most important and affected networks in Alzheimer disease (AD). Significant diagnosis by interaction effects were observed in functional connectivity (FC), especially at the level of posterior ventral DN, and specifically, between the bilateral angular gyrus (ANG) and calcarine (CAL), and precuneus and middle occipital gyrus (MOG). Post hoc analysis showed discrepancies between women and men observed in the AD vs mild cognitive impairment comparison, such as the left ANG–left MOG and right ANG–CAL, where they showed an opposite direction of FC.

Despite the large-scale efforts to improve drug development, the options for patients with AD remain limited, especially for women, who are disproportionately impacted by the disease. In an interview with 

, Caldwell, director of the Women’s Alzheimer’s Movement Prevention Center at 

, discussed the possibility of future therapeutics directed solely for women, and whether these routes are worth pursuing. Additionally, she provided insight on prevention methods for both men and women with the disease, and whether they can be tailored to certain brain regions.

REFERENCE
1. Cieri F, Yang Z, Kinney J, Cummings JL, Cordes D, Caldwell JK. Interaction effect of sex and diagnosis on functional connectivity within the default network in healthy controls, mild cognitive impairment, and Alzheimer disease. Presented at: 2022 Alzheimer’s Association International Conference; July 31 to August 4; San Diego, CA. 68142

Videos

The director of the Women’s Alzheimer’s Movement Preventer Center at Cleveland Clinic provided perspective on the possibility of gender-specific therapies to overcome disparities in Alzheimer disease. [WATCH TIME: 3 minutes]

The Realities of Gender-Targeted Therapeutics for Alzheimer Disease: Jessica Caldwell, PhD

Previous studies have shown that about two-thirds of people diagnosed with Alzheimer disease (AD) are women; however, the reasons for these sex disparities remain unsolved. To better understand these issues, a group of investigators explored functional connectivity of the default network (DN), one of the most important and affected networks in AD. The study compiled individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, clinically diagnosed as either healthy controls, or having mild cognitive impairment (MCI) or AD.

, the analysis used Pearson correlations to characterize functional connectivity between several regions of interest, including bilateral angular gyrus (ANG), calcarine (CAL), precuneus (PCUN), medial orbital frontal gyrus, and bilateral occipital gyrus. All told, the findings showed distinct effect sizes and/or opposite direction effects in women compared with men. Left ANG-CAL and left ANG-PCUN connectivity had medium effect (

 >.05) for men in the MCI vs HC comparison, although small effect (

Caldwell, director of the Women’s Alzheimer’s Movement Prevention Center at 

, discussed the findings in greater detail, along with the reasons for the study, and the most notable findings of which the clinical community should be aware. She also touched on how these new data adds to the growing knowledge of sex differences and their long-term effects on late-life cognition.

The director of the Women’s Alzheimer’s Movement Prevention Center at Cleveland Clinic provided insight on data presented at AAIC 2022 that evaluated the interaction effect of sex and diagnosis on functional connectivity in various cognitive stages. [WATCH TIME: 3 minutes]

Using Functional Connectivity and the Default Network to Uncover Sex-Based Differences: Jessica Caldwell, PhD

"The simplistic argument is that we’ve been studying men only, and then men and women, for quite a long time. We don’t need that comparison. Of course, that argument could be made with other divisions as well."

, was awarded a granted expected to total $1.8 million from the National Institutes of Health to study the interactive effects of gender and sex on biological processes in Alzheimer disease (AD). Over the next 4 years, Caldwell and her team will examine how gender-linked stress exposure and estrogen may interact to impact memory, inflammation in the body, and brain activation and connectivity in women at risk for AD.

Caldwell currently serves as the director for the Women’s Alzheimer’s Movement Prevention Center at 

, which celebrated its 1-year inauguration with the grant. Since opening its doors in summer 2020, the center has welcomed women from 40 states across the country and received honorable mention in Fast Company’s list of 2021 

. Caldwell hopes that her research will continue to drive change within the space and create more all-women and women-inclusive trials.

she provided perspective on the ways genetics impact AD trial design and the goal of enrolling homogenous populations. She also pled her case for why the space needs more studies focused on the effects of AD in women, considering women are at a higher risk for the disease.

The director of the Women’s Alzheimer’s Movement Prevention Center at Cleveland Clinic discussed the role genetics play in Alzheimer disease and the importance for all-women trials. [WATCH TIME: 2 minutes]

Prioritizing Women and Genetics in Alzheimer Disease Trials: Jessica Caldwell, PhD

"Trying to personalize and capture the whole person when they come into clinical trials will be very important. That includes genetics, but does not rely on genetics as the mechanism of further tailoring development of drugs."

A significant hurdle in developing therapeutics and care models for Alzheimer disease (AD) that work for people of all ethnic and racial backgrounds is the recruitment and retention of traditionally underrepresented groups in clinical trials. Previous research indicating a higher risk of AD among certain groups of individuals has forced clinicians to stress the importance of inclusion. While most clinical trials aim to have a homogenous population, excluding these patients could have potentially harmful long-term effects on the effectiveness of and process for future approved medications.

, understands there are complexities in recruiting these patients to these clinical trials. Caldwell, the director of the Women’s Movement Prevention Center at 

, will head a recently announced project that aims to uncover why women are more likely to be impacted by AD and how to reduce that risk. She anticipates that the data from this study will provide evidence linking greater lifetime gender-based stressor exposures to poorer verbal memory in women at risk for AD, as well as processes likely to contribute to sex and gender disparities in the disease.

Caldwell discussed the complexities in compiling relatively homogenous populations for AD clinical trials. She noted that while genetics can complicate these studies, they are crucial to understanding the true efficacy of investigational interventions.

The director of the Women’s Prevention Center at Cleveland Clinic discussed why understanding genetics may help drug development of Alzheimer disease treatments. [WATCH TIME: 2 minutes]

Improving Alzheimer Disease Trials With Genetics: Jessica Caldwell, PhD

"The research needs to focus on a number of different things, including whether or not we are inviting people to the research in the same way. Lots of studies have shown that White people come to the research because they’re recruited through the clinic while non-White people get recruited because we’re supposed to recruit non-White people. It’s a very different way to sample people in terms of their concerns and risks."

Although it has been previously documented that the frequency of Alzheimer disease (AD) dementia is higher in women, sex differences in the incidence of AD dementia are less than clear. To better understand the effects of gender and sex in AD, the National Institutes of Health (NIH) awarded a 4-year, $1.8-million grant to Jessica Caldwell, PhD, director, Women’s Alzheimer’s Movement Prevention Center, 

. The grant marked the 1-year anniversary of the center’s opening, which was the first prevention center designed specifically for women.

Caldwell will use the grant to study how gender-linked stress exposure and estrogen may interact to impact memory, inflammation in the body, and brain activation and connectivity in women at risk for AD. She hopes that the findings will help to inform development of interventions targeting stress and inflammation to reduce AD risk.

Caldwell discussed the details of the grant and how it will be utilized. She also provided insight on some of the biggest remaining questions regarding the impact of genetics and sex in AD risk and prevalence.

The director of The Women’s Alzheimer’s Movement Prevention Center at Cleveland Clinic discussed her recently awarded NIH grant and her work to understand why women are more likely to be impacted by Alzheimer disease. 

Jessica Caldwell, PhD

Articles

The Realities of Gender-Targeted Therapeutics for Alzheimer Disease: Jessica Caldwell, PhD

Using Functional Connectivity and the Default Network to Uncover Sex-Based Differences: Jessica Caldwell, PhD

Prioritizing Women and Genetics in Alzheimer Disease Trials: Jessica Caldwell, PhD

Improving Alzheimer Disease Trials With Genetics: Jessica Caldwell, PhD

Studying Effects of Gender and Sex in Alzheimer Disease: Jessica Caldwell, PhD

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