Pilot Study Links Alzheimer’s with Vascular Changes in Neck

The researchers believe their study is the first to associate jugular venous reflux (JVR) — a hemodynamic abnormality in these veins — with a higher frequency of white matter changes in the brain, says senior author Robert Zivadinov, MD, PhD, professor of neurology.

Using Doppler ultrasound and magnetic resonance imaging, the researchers assessed 12 patients with Alzheimer’s disease, 24 with mild cognitive impairment and 17 elderly controls.

Although results must be validated through larger studies, this research could potentially lead to a better understanding of Alzheimer’s and other aging-related neurological disorders.

Age-related white matter changes have long been associated with dementia and faster cognitive decline, and Alzheimer’s patients have more white matter lesions than healthy people, Zivadinov explains.

If validated, the observed JVR-white matter association “also could be significant for the development of new diagnostic tools and treatments for pathological white matter lesions,” notes first author Ching-Ping Chung, assistant professor of neurology at National Yang-Ming University in Taiwan.

Another finding suggests that JVR is associated with dirty-appearing white matter, which is thought to represent early-stage lesion formation.

The researchers believe this is one of the first studies to explore the impact of dirty-appearing white matter in the elderly, says second author Clive Beggs, professor of medical engineering at the University of Bradford in the United Kingdom, adding that the significance of this research requires additional study.

White matter changes have a direct relationship to the buildup of amyloid plaque, long seen as central to the development of Alzheimer’s disease.

“The accumulation of amyloid plaque may result from the inability of cerebrospinal fluid to be properly cleared from the brain,” says Beggs.

JVR, which is more common in the elderly, may be the culprit leading to impaired cerebral venous drainage.

The process begins as the internal jugular vein valves do not open and close properly, causing the pressure gradient to reverse the direction of blood flow in the veins, in turn causing blood to leak backwards into the brain.

JVR’s accumulated effects on cerebral circulation may take many years to develop, Zivadinov says, noting that “patients are likely to be asymptomatic for a long time.”

This would explain why Zivadinov’s team previously found structural and hemodynamic changes of the extracranial venous system in both healthy controls and people with a variety of neurological diseases.

The research, “Jugular Venous Reflux and White Matter Abnormalities in Alzheimer's Disease: A Pilot Study,” has been published in the Journal of Alzheimer’s Disease.

Other UB co-authors, all with the Department of Neurology’s Buffalo Neuroimaging Analysis Center, include Deepa P. Ramasamy, MD, clinical trial neuroimager and senior clinical trial research assistant; Niels Bergsland, integration director; and Michael G. Dwyer, director of technical imaging.

Additional colleagues from the University of Bradford, the Taipei Veterans General Hospital and the National Yang-Ming University School of Medicine also contributed.