“For the first time, we found that better blood flow makes the hippocampus area stiffer,” stated Mehmet Kurt, University of Washington Associate Professor and Kurtlab Director. Kurt recently discovered, working with his lab team as co-researchers, an autonomous relationship between circulation and biomechanics of the hippocampus area that is involved in remembering and learning function within the brain. The findings of the study have very important implications, which can lead to an Alzheimer’s disease diagnosis several years prior to when patients present symptoms of memory loss.
The memory center of the brain or the hippocampus is one of the first parts of the brain attacked by Alzheimer’s disease. The neurodegenerative disease slowly destroys mental powers and makes patients unable to execute basic functions. Though softening of the hippocampus has been observed in Alzheimer’s patients, Kurt’s researchers found the astounding correlation: more blood flow is paired with greater stiffness in this area. This was the astounding finding made possible with new imaging technology, including magnetic resonance elastography (MRE), which combines magnetic resonance imaging (MRI) with sound waves to gauge stiffness of tissues.
UW Center for Human Neuroscience and Icahn School of Medicine at Mount Sinai scientists imaged 17 young adults, between 22 and 35 years, with MRE scans. Result was amazing. “The hippocampus is the only part of the brain that shows this relationship between blood flow and stiffness,” said Caitlin Neher, lead author of the study, a Ph.D. candidate. She credited this bizarre effect to the extremely active metabolism of the hippocampus, which is different from the rest of the brain.
The research forms part of a series of expanding research connecting cerebral blood flow and brain function. Hypoperfusion, or reduced blood flow, is a characteristic of Alzheimer’s disease, which occurs normally years before cognitive impairment symptoms. In accordance with review on cerebral blood flow in Alzheimer’s, in Alzheimer’s disease, 10–20% declines from baseline flow are the norm in early disease and correlate directly with the level of cognitive impairment. In a turnabout, mouse models of Alzheimer’s have demonstrated that normalization of blood flow improves short-term memory, showing the pivotal function of vascular integrity in brain performance.
So why would blood perfusion make a difference to hippocampal stiffness? The reason is in the biomechanical intricacy of brain tissue. MRE quantifies tissue elasticity by inducing mechanical waves and observing how they propagate in tissue. Hippocampal stiffness is a measure of deformation resistance itself a function of vascular and cellular contents. A change in blood flow might alter the biomechanical environment for regulating the accommodation of hippocampal learning and memory function.
The present study is part of a complete program for the application of MRE as a disease diagnostic tool within the field of neurology. MRE has already been applied in the past in an effort to measure liver fibrosis and is more commonly applied in the research of the brain. Experiments have proven that brain stiffness decreases with increased age as well as with illness such as multiple sclerosis and dementia. A recent review placed in broad relief on the potential of MRE for differential diagnosis of several forms of dementia based on characteristic stiffness change patterns. In Alzheimer disease, the method can provide noninvasive early hippocampal diagnosis for an intervention window.
The hippocampus itself consists of non-homogenous subregions with various functions and metabolic requirements. Another study on hippocampal metabolic networks of the hippocampus discovered that anterior and posterior subregions have distinct patterns of glucose metabolism and connection. These distinctions will interact with the interaction between blood flow and stiffness, so the findings will be even more complex.
Where Kurt’s team experimented with young healthy adults, the future would be to include the elderly and Alzheimer’s patients. Funding by institutions like UW Medicine would make it possible to determine MRE’s potential as a clinical diagnostic tool. “We want to better understand this link between brain stiffness and blood flow and come up with diagnostic criteria,” Neher added.
This discovery of the significance of blood flow and stiffness within the hippocampus is not only a scientific breakthrough, but also a paradigm shift to predict and diagnose Alzheimer’s disease. It is through destroying high-technology imaging modalities against knowledge in brain biomechanics that researchers are de-mystifying the disease in an orderly manner. The path here will not be smooth, but the point is that half a billion potential human beings being early diagnosed and treated could become a reality.
