The main risk factors for Alzheimer’s disease affect men more than women

Overview: Men with the BIN1 Alzheimer’s genetic risk factor and poor vascular health showed a greater and more rapid decline in memory than women.

Source: University of Alberta

Scientists at the University of Alberta have found that key risk factors for Alzheimer’s disease affect men and women very differently.

“Two types of Alzheimer’s risk act differently for men and women, and dramatically so,” said Mackenzie Heal, a neuroscience master’s student in the Neuroscience and Mental Health Institute graduate program and lead author of the recent study.

In the large-scale study, the researchers used neuroinformatics to analyze data from 623 older adults over 44 years of their lives, ages 53 to 97, drawn from the Victoria Longitudinal Study database.

The researchers looked at two known risk factors for Alzheimer’s disease: a gene called bridging integrator 1 (BIN1) and vascular health, as measured by pulse pressure. They then compared a known early symptom, episodic memory loss, in men and women. Episodic memory refers to our recollection of everyday events, such as what we ate for breakfast the previous day.

“In the study, we found that memory loss was negatively impacted by poor vascular health (high pulse pressure) for everyone,” explains Heal.

“Second, for those with BIN1 genetic risk, even a good pulse pressure cannot protect them from amnesia. And third, for men at BIN1 genetic risk and poor vascular health, the slopes were much steeper, showing a sharp decline in memory, while women did not.”

Women are more likely to be diagnosed with Alzheimer’s

This finding is unexpected because women are more likely to be diagnosed with Alzheimer’s than men. There are several reasons for this, one being that women live longer than men, but there are also other neurobiological and hormonal changes in middle age that play a role.

Discovering that these two risk factors do not have the same impact on women highlights the importance of considering differences between men and women when diagnosing and treating Alzheimer’s disease, says Heal’s supervisor and study co-author Roger Dixon, professor of psychology in the Faculty of Science and NMHI member.

“Precision health approaches are needed. Different treatment may be needed for a person with one risk profile versus another, and this has important implications for prevention and treatment.”

A treacherous start

The researchers looked at 44 years of data because Alzheimer’s disease has “a treacherous onset,” Dixon notes.

“That means it starts long before we can diagnose it. Not just five years, but 10, 15, 20 years before diagnosis, there are changes in the brain that are early signals of the disease.

“One thing a lot of researchers are doing is striving to find those individuals who are most at risk for Alzheimer’s long before they get it, because once they get it, there’s not much we can do except treat some of the symptoms.” relieve,” says Dixon.

This shows a brain
This finding is unexpected because women are more likely to be diagnosed with Alzheimer’s than men. The image is in the public domain

The problem is how to identify the people who are at high risk.

“Fortunately, there are a number of large-scale longitudinal studies where we follow older adults and produce trajectories of change over time in factors of significance for Alzheimer’s disease – and this is where Mackenzie’s paper fits in,” says Dixon.

“We need neuroinformatics and analytical technologies that help us identify combinations of risks that are most problematic for individuals.”

Pathways to prevention

According to Dixon, another complicating factor is that everyone accumulates some risk factors as they age, and there are multiple risk factors that can lead to Alzheimer’s disease. So there’s no single risk factor that will tell researchers who will get it or not — it’s a combination that unfolds over time.

But if they have the right data, they can track and identify who is most at risk, he says.

“There are many pathways leading to Alzheimer’s disease, so the study looked alone and together at both genetic risk and vascular health,” says Dixon.

“Some roads lead to Alzheimer’s disease and others lead away from it. What we’re doing here is to find subtypes, as defined by these risk factors, and identify which ones are most likely to benefit from which kind of risk intervention or risk reduction intervention.

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“We need to be able to determine the risk factors much earlier,” Heal adds, “because there is currently no cure for Alzheimer’s disease.”

About this news about Alzheimer’s disease

Writer: Ramona Czakert Franson
Source: University of Alberta
Contact: Ramona Czakert Franson – University of Alberta
Image: The image is in the public domain

Original research: Open access.
“Bridging Integrator 1 (BIN1, rs6733839) and sex are moderators of vascular health predictions of memory aging trajectories” by Mackenzie Heal et al. Journal of Alzheimer’s disease


Abstract

Bridging Integrator 1 (BIN1, rs6733839) and Sex are moderators of vascular health predictions of memory aging pathways

Background: A promising risk loci for sporadic Alzheimer’s disease (AD), Bridging Integrator 1 (BIN1), is believed to act through the tau pathology pathway.

Objectively: We investigate BIN1 risk for a moderating role with vascular health (pulse pressure; PP) and gender in predictions of episodic memory trajectories in asymptomatic aging adults.

methods: The sample included 623 participants (baseline mean age = 70.1; 66.8% female) with a longitudinal band of 44 years (53-97 years). With an established latent memory variable arranged as individualized trajectories, we applied Mplus 8.5 to determine the best fit longitudinal growth model. Principal analyzes were performed in three sequential phases to examine: 1) memory trajectory prediction by PP, 2) moderation by BIN1 genetic risk, and 3) stratification by gender.

Results: We first confirmed that good vascular health (lower PP) was associated with higher memory levels and more superficial decline and that men were more severely affected by deteriorating PP in both memory performance and longitudinal decline. Second, the PP prediction of memory trajectories was significant for BIN1 C/C and C/T carriers, but not for individuals with the highest AD risk (T/T homozygotes). Third, when further stratified by gender, the BIN1 moderation of memory prediction by PP was selective for females.

Conclusion: We observed a novel interaction where BIN1 (linked to tauopathy in AD) and sex sequentially moderated a benchmark PP prediction of differential memory decline in asymptomatic aging. This multimodal biomarker interaction approach, broken down by gender, may be an effective method to improve the precision of AD genetic risk assessment.

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