Translational Value of Neuroimaging for Alzheimer’s Disease

Clinical diagnosis of Alzheimer’s disease (AD) is through a comprehensive cognitive testing, assessment of medical and family history, and symptom tracking. The true diagnosis of Alzheimer’s disease is actually done at autopsy.

different brain scan imagesThe classic signs of Alzheimer’s disease are amyloid plaques and neurofibrillary tangles. The amyloid plaques build up outside of the nerve cells in the brain and it is thought that interaction of the nerve cell with the plaque causes nerve cells to make tangles inside the cell. The tangles cause the cells to degenerate and die. We have evidence that these amyloid plaques start occurring in people’s brains one to two decades before any symptoms like memory loss begin to show.

From a clinical symptom perspective, especially in the early disease stages, many diseases present clinically very similar to AD, like Frontal Lobe Dementia or Vascular Dementia, but without true AD pathology of amyloid and tangles. Before we utilized the above imaging biomarkers, clinical diagnostic methods were not precise or accurate enough to give someone a solid AD diagnosis. Now, the use of imaging and plasma biomarkers allow AD diagnosis more definitively by either viewing these plaques with PET imaging or analyzing cerebrospinal fluid from a spinal tap to look for these disease-inducing beta amyloid proteins. It is a technological triumph that we can use these methods, but there is a huge problem with them in clinical practice as well as clinical trials.

First, PET Imaging gives us a fantastic look at the human brain in vivo, but requires exposure to X-ray radiation, is extremely expensive, and requires a health center to possess that technology to begin with. Most medical centers do not actually have access to PET Imaging systems or imaging tracers required to highlight these proteins in human brain, and this diagnostic test is not always covered by insurance. While PET is expensive and exposes individuals to radiation, the less expensive diagnostic method - analysis of spinal fluid - requires a spinal tap. Spinal taps are painful, can cause uncomfortable side effects and are not always easy to complete on potentially non-compliant patients. Alzheimer's symptoms can cause confusion at the best of times, so needing to be still while under a great deal of pain may be impossible, if not very difficult.

At the moment, most of the AD clinical trials on potential treatments are being conducted using the participation of individuals who likely have not been confirmed to have biomarkers of AD, for the reasons stated above. As a result, success rate may be artificially low. The treatments, medications or otherwise, might work on AD but not for other forms of dementia, skewing the data to look more like a placebo effect. Researchers aren’t currently able to justify the costs and risks of the more accurate tests, resulting in a barrier to scientifically accurate clinical trials. However, VA/UCSF researchers seem to have found the answer to this conundrum. Utilizing a large data set of potentially AD affected individuals, together with healthy individuals and individuals with early AD-like clinical symptoms, we compiled MRI scans and were able to detect a way to recognize the same biomarkers through the much safer, much more financially and geographically accessible MRI technologies that already exist. Not only are MRIs safer, with no radiation exposure, but these brain-scanning diagnostic tools are much more comfortable to endure by the AD study participants. This is extremely important because this allows clinicians and researchers alike to truly diagnose AD etiology in dementia-affected or early symptomatic populations via an additional screening step.

Future clinical studies will be able to afford to utilize the more precise PET imaging and/or spinal tap diagnostic tools if they can limit the number of people they are testing via this initial checkpoint. This will allow for greater diversity and accuracy within clinical trials. Also, because this test is so low-risk to patients, the ability of healthy individuals to be preemptively screened will allow physicians to potentially be proactive and administer preventive medications or life-style modifications to slow the progress of the toxic effects of these proteins before cell death begins, and more importantly, before devastating symptoms arise.

This is incredibly exciting because when the cause of degeneration is discovered earlier in the progression, there is a much better prognosis for the individuals. Neurodegeneration can be permanent, so it is extremely crucial to not miss an active neuroprotective window where interventions are much more successful. These brain scans also have applications that would not be obvious at first glance. There are certain individuals with these biomarkers who are somehow free of any symptoms and otherwise quite healthy. If we begin to scan more otherwise healthy brains in order to discover these biomarkers before illness becomes apparent, we will also have the ability to find AD-marked yet symptomless individuals. Studying these brains will allow us to potentially find new ways to fight Alzheimer’s, once we know how the brain is being protected in these rare cases.

It is incredibly important that we educate the public about how amazing this breakthrough is. In fact, it could save lives. More public support behind cost-effective, accurate diagnostic scans of the brain may bring about further funding for researchers working towards AD treatments. Also, public awareness is likely to lead towards a push to a different diagnostic standard, and will hopefully inspire more people to contribute to science by becoming research participants, even if they don’t currently have neurodegenerative symptoms. These discoveries were only made possible through the application of AI and machine learning. These research tools require a great deal of data in order to be effective. The brain, as you may know, is an extremely complicated organ, and there are so many questions that still exist. The more brain scans we have access to, the more we can compile data, and the more data we have, the more exciting discoveries we can make. We hope that with the participation of patients and further collaboration with researchers both in academia and biotechnology that we can uncover much more about the brain.