New Imaging Techniques Could Identify Connection in AD and Vascular Disease

Radiologists play important role in identifying vascular dementia

Laura Burns Eisenmenger, MD

RSNA News highlights the research being done in brain imaging to support Alzheimer's disease and dementia diagnosis and treatment. This is part three in a series of stories on this topic. Read part one, part two and part four.

Vascular findings have long been associated with Alzheimer’s disease (AD) and other dementias, but when it comes to quantification, a radiologist’s role is complicated.

“In medical school, we were taught that vascular dementia is the second most common type of dementia,” said Laura Burns Eisenmenger, MD, assistant professor of neuroradiology at the University of Wisconsin in Madison. “But how often do radiology reports findings state, ‘this is vascular dementia’?”

As Dr. Eisenmenger points out, it’s currently unclear whether cardiovascular disease causes, precipitates, amplifies, precedes or simply coincides with AD. Dr. Eisenmenger demonstrated in an
RSNA 2023 session how radiologists can identify patterns with common clinical techniques—and how researchers are developing new methods to define reliable biomarkers.

The Importance of White Matter Hyperintensities

In the clinical setting, the preferred modality is T2-weighted imaging, such as T2 FLAIR, Dr. Eisenmenger said.

“This imaging technique emphasizes parenchymal abnormalities and what we think of in clinical imaging is white matter hyperintensities— but are they always a marker of vascular disease? The answer is not always, but they are a good indicator.”

White matter hyperintensities (WMH) are more common in people who have risk factors for stroke, even in those who don’t show clinical signs of dementia. They also tend to increase with age and to some extent can be considered “normal” in older patients.

Dr. Eisenmenger noted that, when reporting WMH, adhering to a specific grading scale isn’t critical as long as radiologists are consistent.

“At our institution, we report whether or not the degree of WMH seems greater than expected for the patient’s age.”

brain and alzheimers disease month image

In addition to grading, examining the volume of WMH can be useful and software can assist with quantifying volume. As for patterns of WMH, different distributions can indicate different etiologies. The Fazekas scale, for example, differentiates patterns of deep white matter or subcortical WMH as associated with chronic small vessel ischemia, whereas periventricular WMH may indicate a combination of demyelination, ependymitis granularis and subependymal gliosis.

T2-weighed imaging can demonstrate additional pathologies such as damage to small blood vessel walls, breaches of the barrier etween the cerebrospinal  fluid and the brain, and loss or deformation of the myelin sheath. T2*-weighted imaging, as opposed to susceptibility-weighted imaging, is another technique that is especially useful for cerebral amyloid angiopathy, Dr. Eisenmenger noted. The condition is apparent in 80%-90% of patients with AD.

“Whenever I ever see a pattern of AD on any clinical imaging, I start to super-hunt for microhemorrhages,” Dr. Eisenmenger said.

Imaging Techniques for the Future

In the laboratory setting, Dr. Eisenmenger and fellow researchers are exploring advanced methods like 4D flow MR to develop whole-brain assessments that can translate to multiple measures of vascular health. Using a phase-contrast technique with both a blood flow vector and a temporal component, they’ve captured both volumetric angiographic and quantitative assessment of blood flow velocities in a single acquisition.

“Perfusion is impacted by metabolism,” Dr. Eisenmenger said. “We know that as cells are dying, the metabolism is going down. In that case, are we measuring actual vascular disease, or just that decrease in metabolism?”

Examining shear stress, pulsatility, pressure gradients and vessel area, the team saw higher pulse wave velocities in patients with AD than in age-matched controls. “We took it a step further with an impact group—people with family members suffering from AD, and a positive amyloid test, who are cognitively normal,” Dr. Eisenmenger said. “The idea was to show that even before someone has any cognitive impairment, having those risk factors meant that they had more vascular disease. The question is whether patients have co-occurring disease or whether vascular disease is impacting Alzheimer’s risk?"

For More Information

Read previous RSNA News stories on Alzheimer's disease research: