Abnormal blood vessel growth in the brain may be an early diagnostic sign of cognitive impairment

Gender differences define how the human brain ages, and telltale biomarkers in the blood may be strongly suggestive of cognitive impairment and dementia, according to a comprehensive new study involving more than 500 people.

Just as skin wrinkles and muscles sag, the human body’s massive network of vasculature can be waylaid by the vagaries of age. Indeed, growing older can impact the very process by which healthy new blood vessels are made, resulting in aberrant angiogenesis—an abnormal and disordered formation of new vasculature.

A team of neuroscientists in the United States and Canada was able to uncover differences in brain aging between men and women by pinpointing biomarkers—fragments of blood vessel growth factors—the remains of aberrant angiogenesis in their blood. These scientists suggest that an ailing angiogenesis system offers a new target for early intervention against neurodegenerative disorders.

“Aberrant angiogenesis can contribute to the development of cognitive impairment,” writes neuroscientist Dr. Abel Torres-Espin, lead author of a new analysis published in Science Translational Medicine.

Many forms of dementia and cognitive impairment are linked to abnormalities in small vessels and capillaries in the brain. Vascular dementia is a prime example of a brain disorder that develops as a direct consequence of blood vessel impairment. But Alzheimer’s disease is among a host of others that are also marked by damaged vasculature in the brain.

As people age, vessels can lose their tensile strength as well as undergo a decline in density, and this can be accompanied by an overall slowdown in angiogenesis. While these problems do not become pervasive for many people, for some they contribute to irreversible brain disorders.

“With aging, numerous pathologies result in abnormal blood vessels across calibers of vessels, from capillaries to large vessels,” Torres-Espin stated. “The pathologies present in small blood vessels are among the most insidious and yet most prevalent and detrimental consequences of aging.”

Still, Torres-Espin and colleagues offer a ray of hope: The task now, they say, is to conduct additional studies to tease out how to exploit aberrant angiogenesis as a druggable target.

In the new study, the team studied brain imaging, clinical data, and blood markers of angiogenesis, including the family of VEGF growth factors and their receptors. VEGF stands for vascular endothelial growth factor. VEGF is critically necessary for angiogenesis and plays a central role in stimulating the growth and development of new blood vessels.

There are multiple types of VEGF that contribute to angiogenesis, with the most prominent being VEGF-A, but also VEGF-B, VEGF-C and placental growth factor, PlGF. Each has a slightly different role and binding affinity to VEGF receptors.

The research identified two main pathways to brain abnormalities—aberrant angiogenesis and sex-specific patterns in the trajectories of VEGF growth factors in the brain.

“The trajectories of some markers of angiogenesis are associated with better executive function and less brain atrophy in younger women, but not in men. However, these trajectories reversed at the age of 75, suggesting that both sex and age are critical variables [for future] study,” Torres-Espin wrote.

“We used unsupervised machine learning and linear mixed effects models and found sexually dimorphic and age-dependent associations between markers of angiogenesis and brain aging outcomes,” he continued.

The study revealed that angiogenesis markers weren’t the only ones that showed differences across a gender divide. For example, about 30% of participants were carriers of the APOE4 genotype with significant differences between men and women.

APOE4 is strongly associated with an increased risk of developing Alzheimer’s disease. In the study, men represented a higher proportion of APOE4 carriers—34.2%—compared with 25.6% among women. APOE4 is also linked with elevated cholesterol levels, particularly low-density lipoprotein, or LDL, the so-called bad form of the compound, which is additionally associated with obstructed arteries.

At the beginning of the research project, the Clinical Dementia Rating scale showed that 73% of participants were considered to be functionally normal with no evidence of cognitive impairment or dementia at first visit. However, by the end of the study, only 66% were considered functionally normal. The average age was 71 at the beginning of the analysis, and 77 by the end of the study.

There were statistically significant differences between men and women for Clinical Dementia Rating scores at both first and last visit. A higher proportion of men presented with signs of cognitive impairment at both visits.

“Most studies addressing angiogenesis and cognitive impairment focus on model organisms,” added Torres-Espin, an assistant professor at the University of Waterloo in Ontario, Canada, referring to animal models. The team’s newly published research focuses on human subjects—and more of these kinds of studies are needed, the team said.

Along with the University of Waterloo, a large collaborative group of medical scientists contributed to the new study from leading research centers, most of them in the United States. Scientists hailed from the University of California, San Francisco; the University of California, Davis, and the Icahn School of Medicine at The Mount Sinai Hospital in New York City, among other institutions.

Torres-Espin concluded that the team’s research serves as a model for other centers to conduct similar analyses because the “approach we adopted in this study provides a blueprint for the investigation of plasma biomarkers of vascular neurodegenerative disease, with great promise for future diagnostics and clinical trial interventions.”

© 2025 Science X Network

Gender differences define how the human brain ages, and telltale biomarkers in the blood may be strongly suggestive of cognitive impairment and dementia, according to a comprehensive new study involving more than 500 people.

Just as skin wrinkles and muscles sag, the human body’s massive network of vasculature can be waylaid by the vagaries of age. Indeed, growing older can impact the very process by which healthy new blood vessels are made, resulting in aberrant angiogenesis—an abnormal and disordered formation of new vasculature.

A team of neuroscientists in the United States and Canada was able to uncover differences in brain aging between men and women by pinpointing biomarkers—fragments of blood vessel growth factors—the remains of aberrant angiogenesis in their blood. These scientists suggest that an ailing angiogenesis system offers a new target for early intervention against neurodegenerative disorders.

“Aberrant angiogenesis can contribute to the development of cognitive impairment,” writes neuroscientist Dr. Abel Torres-Espin, lead author of a new analysis published in Science Translational Medicine.

Many forms of dementia and cognitive impairment are linked to abnormalities in small vessels and capillaries in the brain. Vascular dementia is a prime example of a brain disorder that develops as a direct consequence of blood vessel impairment. But Alzheimer’s disease is among a host of others that are also marked by damaged vasculature in the brain.

As people age, vessels can lose their tensile strength as well as undergo a decline in density, and this can be accompanied by an overall slowdown in angiogenesis. While these problems do not become pervasive for many people, for some they contribute to irreversible brain disorders.

“With aging, numerous pathologies result in abnormal blood vessels across calibers of vessels, from capillaries to large vessels,” Torres-Espin stated. “The pathologies present in small blood vessels are among the most insidious and yet most prevalent and detrimental consequences of aging.”

Still, Torres-Espin and colleagues offer a ray of hope: The task now, they say, is to conduct additional studies to tease out how to exploit aberrant angiogenesis as a druggable target.

In the new study, the team studied brain imaging, clinical data, and blood markers of angiogenesis, including the family of VEGF growth factors and their receptors. VEGF stands for vascular endothelial growth factor. VEGF is critically necessary for angiogenesis and plays a central role in stimulating the growth and development of new blood vessels.

There are multiple types of VEGF that contribute to angiogenesis, with the most prominent being VEGF-A, but also VEGF-B, VEGF-C and placental growth factor, PlGF. Each has a slightly different role and binding affinity to VEGF receptors.

The research identified two main pathways to brain abnormalities—aberrant angiogenesis and sex-specific patterns in the trajectories of VEGF growth factors in the brain.

“The trajectories of some markers of angiogenesis are associated with better executive function and less brain atrophy in younger women, but not in men. However, these trajectories reversed at the age of 75, suggesting that both sex and age are critical variables [for future] study,” Torres-Espin wrote.

“We used unsupervised machine learning and linear mixed effects models and found sexually dimorphic and age-dependent associations between markers of angiogenesis and brain aging outcomes,” he continued.

The study revealed that angiogenesis markers weren’t the only ones that showed differences across a gender divide. For example, about 30% of participants were carriers of the APOE4 genotype with significant differences between men and women.

APOE4 is strongly associated with an increased risk of developing Alzheimer’s disease. In the study, men represented a higher proportion of APOE4 carriers—34.2%—compared with 25.6% among women. APOE4 is also linked with elevated cholesterol levels, particularly low-density lipoprotein, or LDL, the so-called bad form of the compound, which is additionally associated with obstructed arteries.

At the beginning of the research project, the Clinical Dementia Rating scale showed that 73% of participants were considered to be functionally normal with no evidence of cognitive impairment or dementia at first visit. However, by the end of the study, only 66% were considered functionally normal. The average age was 71 at the beginning of the analysis, and 77 by the end of the study.

There were statistically significant differences between men and women for Clinical Dementia Rating scores at both first and last visit. A higher proportion of men presented with signs of cognitive impairment at both visits.

“Most studies addressing angiogenesis and cognitive impairment focus on model organisms,” added Torres-Espin, an assistant professor at the University of Waterloo in Ontario, Canada, referring to animal models. The team’s newly published research focuses on human subjects—and more of these kinds of studies are needed, the team said.

Along with the University of Waterloo, a large collaborative group of medical scientists contributed to the new study from leading research centers, most of them in the United States. Scientists hailed from the University of California, San Francisco; the University of California, Davis, and the Icahn School of Medicine at The Mount Sinai Hospital in New York City, among other institutions.

Torres-Espin concluded that the team’s research serves as a model for other centers to conduct similar analyses because the “approach we adopted in this study provides a blueprint for the investigation of plasma biomarkers of vascular neurodegenerative disease, with great promise for future diagnostics and clinical trial interventions.”

© 2025 Science X Network