Brain’s ‘Wakeful Rest’ network may hold key to Alzheimer’s risk

Overview: In women, parts of the default mode network responsible for memory retrieval and recall, and spatial cognition were more likely to be connected to the overall DMN network. The patterns of connectivity, correlated with brain structures associated with short-term memory problems, resembled changes seen in preclinical Alzheimer’s disease.

Source: Yale

If you’ve ever let your mind wander, you rely on the brain’s default mode network (DMN). Scientifically, the DMN is a connection of brain regions that interact when a person is in a state of awake rest.

This network is important for the use of our short-term memory and raises the question: do changes in the DMN play a key role in the short-term memory loss observed in the progression of Alzheimer’s disease (AD)? And is the DMN affected differently in women and men?

Women’s Health Research at Yale (WHRY) contributor Carolyn Fredericks, MD, assistant professor of neurology, has worked to understand AD and why it disproportionately affects women.

Robust research shows that women clearly have an increased risk of AD compared to men. While there has been a lot of research on AD, there are far fewer studies that take sex differences into account.

Fredericks’ latest study, published in cerebral cortex, specifically examines sex differences in DMN connectivity in healthy aging adults. Fredericks and her team, which included Bronte Ficek-Tani, a sophomore medical student at the University of Washington, set out to identify the differences in these compounds for both women and men, which could provide clues as to why the risk of AD is higher in women.

Previous studies have shown that brain connectivity within the DMN changes in association with symptomatic and preclinical AD, but research on sex differences in such changes is limited. Fredericks’ study also examined how connectivity changes in women and men as they age.

Using data from the Human Connectome Project-Aging, the team analyzed brain scans of patients who were awake. They found differences in how central communication points in the brain work for women and men.

For example, in women, compared to men, the parts of the DMN responsible for memory recall and retrieval, and spatial cognition were more likely to be connected to the overall DMN brain network. These connectivity patterns, correlated with brain structures responsible for short-term memory performance, resembled changes seen in preclinical AD.

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Previous studies have shown that brain connectivity within the DMN changes in association with symptomatic and preclinical AD, but research on sex differences in such changes is limited. The image is in the public domain

In addition, greater sex differences were observed during aging. In their 30s and 40s, women relied more on the connection to the part of the brain responsible for spatial and verbal memory. In the decades surrounding menopause (1940s and 1950s), areas critical to memory retrieval showed higher connectivity to the overall DMN.

Men, on the other hand, showed a different pattern and their highest connectivity was not observed until later in life (60-80 years). For men, the highest connection to the DMN was in a part of the brain responsible for habit formation and long-term memory.

The researchers believe their findings show that women are more dependent on DMN compounds than men for memory and for a longer period of time. A high level of connectivity can cause a network to become strained and more vulnerable to conditions such as AD. This “wear and tear” on the parts of the brain critical to memory could partly explain why women are at higher risk for AD.

Fredericks suggested that these findings could help clinicians and scientists alike better understand memory performance and how it relates to brain networks, even in people without AD, and in turn determine the type of memory loss in AD.

By identifying patterns in the brains of healthy, aging people, scientists may not only have a future target for intervention, but also more time to treat before symptoms are seen.

About this news about Alzheimer’s disease

Writer: Amanda Steffen
Source: Yale
Contact: Amanda Steffen-Yale
Image: The image is in the public domain

Original research: Closed access.
“Sex Differences in Default Mode Network Connectivity in Healthy Aging Adults” by Bronte Ficek-Tani et al. cerebral cortex

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Sex differences in default mode network connectivity in healthy aging adults

Women show an increased lifetime risk of Alzheimer’s disease (AD) compared to men. Characteristic changes in brain connectivity, particularly within the default mode network (DMN), have been associated with both symptomatic and preclinical AD, but the impact of sex on DMN function during aging is poorly understood.

We examined sex differences in DMN connectivity across the lifespan in 595 cognitively healthy participants from the Human Connectome Project-Aging cohort. We used the intrinsic connectivity distribution (a robust voxel-based metric of functional connectivity) and a seed connectivity approach to determine sex differences within the DMN and between the DMN and the whole brain.

Compared to men, women showed higher connectivity with age in posterior DMN nodes and lower connectivity in the medial prefrontal cortex.

Differences were most prominent in the decades surrounding menopause. Seed-based analysis revealed higher connectivity in women from the posterior cingulate to angular gyrus, which correlated with neuropsychological measures of declarative memory and hippocampus.

Taken together, we show significant sex differences in DMN subnetworks across the lifespan, including patterns in aging women that resemble changes previously seen in preclinical AD.

These findings highlight the importance of considering sex in neuroimaging studies of aging and neurodegeneration.

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