Early Diagnosis Helps Fight Alzheimer’s Disease

If you know someone with Alzheimer’s disease or Parkinson’s disease, the diagnosis was most likely based on an educated guess. Until recently, confirmed diagnoses could only be performed with an autopsy. If the presenting symptoms are short-term memory loss, it’s diagnosed as Alzheimer’s disease. If the presenting symptom is a movement or motion disorder, the diagnosis is Parkinson’s disease. If the symptoms are severe, it’s likely Creutzfeldt-Jakob disease (CJD). That’s about as scientific as it has been without a lumbar puncture.

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As it turns out, these brain diseases and their causes are all related. The biggest difference between Alzheimer’s disease and Parkinson’s disease is the region of the brain that is under attack. As these diseases progress, the dividing lines are blurred even more. Creutzfeldt-Jakob disease is in a league of it’s own due to its severity.

Although there is no cure for Alzheimer’s disease, Parkinson’s disease or CJD, getting a diagnosis quickly at an early stage helps patients and their families in many ways. It allows them to access help and support, get treatment to manage their symptoms and plan for the future. Doctors currently use a raft of tests to diagnose Alzheimer’s disease, including memory and cognitive tests and brain scans. The scans are used to check for protein deposits in the brain and shrinkage of the hippocampus, the area of the brain linked to memory. These tests can take several weeks.

When the patient dies, neurodegenerative disease is rarely marked as the cause of the death, so millions of cases are left out of mortality calculations around the world. Millions of additional cases are misdiagnosed or not diagnosed at all.

Despite the incomplete data, neurodegenerative disease is the fastest-growing cause of death in the world. The surge in autism is on a similar trajectory and it is also vastly under-diagnosed.

For these reasons and more, scientists are searching to find new ways to get an early diagnosis of Alzheimer’s disease using easy, noninvasive, low-cost methods. Some of the most recent research has focused on using magnetic resonance imaging, or MRI, scans of the brain. Alzheimer’s is usually diagnosed by the onset of symptoms, but by that time the disease is already underway. Once diagnosed, an MRI scan is able to show brain shrinkage associated with Alzheimer’s disease. Unfortunately, an MRI hasn’t been able to detect early signs of the disease, yet, but hope is on the horizon.

A team of researchers from both the United Kingdom and the United States divided the brain into 115 regions and allocated different features to each region. They developed an algorithm to track changes in those features to accurately predict the onset of Alzheimer’s disease. The team tested its diagnostics system on brain scans from more than 400 people with early-stage and late-stage Alzheimer’s disease and other neurological conditions. The researchers also tested it on data from more than 80 people undergoing tests to diagnose Alzheimer’s. In 98 percent of cases, their MRI-based machine learning system could accurately predict whether a person had Alzheimer’s-related brain changes. They said it was also able to distinguish between early-stage and late-stage Alzheimer’s disease in 79 percent of people.

“This research is not ready as a stand-alone diagnostic tool,” said Rebecca Edelmayer, Ph.D., Senior Director of Scientific engagement for the Alzheimer’s Association. “It is a model that will need more testing in a larger prospectively collected set of data from a diverse group of individuals. For the model to be effective at predicting Alzheimer’s disease and other dementia, it must be applicable to the entire Alzheimer’s disease population.”

Edelmayer also noted that the diagnostic model was developed for a specific type of MRI machine with a particular strength of magnetic field. She said with a variety of machines in use, the results can’t be generalized to all types of scanners. But she said the research is working to improve the early detection of Alzheimer’s disease, Parkinson’s disease, ALS and Creutzfeldt-Jakob disease.

“It is vital that individuals with Alzheimer’s disease receive a diagnosis early in the disease process when treatment may be most beneficial,” she explained. “Plus, early detection of Alzheimer’s disease allows individuals and their families more time to plan for the future, participate in clinical trials and seek community resources.”

A single MRI scan of the brain could diagnose Alzheimer’s disease, according to additional research. The technique is simple and it can identify the Alzheimer’s disease at an early stage.

“Currently no other simple and widely available methods can predict Alzheimer’s disease with this level of accuracy,” said Professor Eric Aboagye, from Imperial’s Department of Surgery and Cancer, who led the research. “Many patients with Alzheimer’s disease at memory clinics have other neurological conditions, but even within this group our system could pick out those patients who had Alzheimer’s disease from those who did not. Waiting for a diagnosis can be a horrible experience for patients and their families. If we could cut down the amount of time they have to wait, make diagnosis a simpler process, and reduce some of the uncertainty, that would help a great deal. Our new approach could also identify early-stage patients for clinical trials of new drug treatments or lifestyle changes.”

The new system identified changes in areas of the brain not previously associated with Alzheimer’s disease, including the cerebellum (the part of the brain that coordinates and regulates physical activity) and the ventral diencephalon (linked to the senses, sight and hearing). This opens new avenues for research into these areas and their links to Alzheimer’s disease.

“Although neurologists already interpret MRI scans to help diagnose Alzheimer’s disease, there are likely to be features of the scans that aren’t visible, even to specialists,” said Dr. Paresh Malhotra, a neurologist at Imperial College Healthcare NHS Trust and a researcher in Imperial’s Department of Brain Sciences. “Using an algorithm able to select texture and subtle structural features in the brain that are affected by Alzheimer’s could really enhance the information we can gain from standard imaging techniques.”

“There is a lot of research going in this direction to try to use MRI or some other kinds of technology to detect early onset of Alzheimer’s,” said Dmitriy Yablonskiy, Ph.D., a professor of radiology at the Mallinckrodt Institute of Radiology at the Washington University School of Medicine in St. Louis.

Yablonskiy and his colleagues say they have a “novel MRI approach” that could be a way to identify brain cell damage in people in the early stages of Alzheimer’s before brain shrinkage is visible and before they have cognitive symptoms. It only takes six minutes to get this diagnostics information.

These researchers published their study results in the Journal of Alzheimer’s Disease three months ago. Their approach involves a new MRI technique that shows brain areas that are no longer functioning because of a loss of healthy neurons. The areas where the neurons were starting to degenerate appeared as darker matter as compared to healthy regions of the brain.

The research team studied 70 people, ages 60 to 90. They included people with no cognitive impairment as well as those with very mild, mild or moderate impairment.

Researchers applied their diagnostics technique to scan the hippocampus, the brain’s memory center and one of the earliest regions affected by Alzheimer’s disease. Their results showed that, in some participants, the region often contained a healthy tissue section with relatively preserved neurons and a “dark matter” dead zone without healthy neurons. Those dark areas showed up in people who tested positive for amyloid buildup, but were not yet experiencing symptoms. Yablonskiy plans to validate its findings with a larger study group.

Alzheimer’s disease is the most common form of dementia, affecting over half a million people in the UK. Although most people with Alzheimer’s disease develop it after the age of 65, people under this age can develop it too. The most frequent symptoms of dementia are memory loss and difficulties with thinking, problem solving and language. Diagnosing patients at an early stage will help patients, families and medical researchers.

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