Promising Techniques for Earlier Alzheimer’s Diagnosis

Recent technologies allow doctors to diagnose the degenerative brain disease earlier.

A close up of the patient in the MRI machine.

Researchers around the country are looking for ways to diagnose Alzheimer's accurately and sooner. Currently, doctors diagnose patients by ruling out all other possible causes of dementia-like symptoms.

Credit: Robert A. Lisak

A dense forest of 100 billion nerve cells flourishes deep within each of our brains. Each of those nerve cells has about 15,000 dendrites that branch out to connect with dendrites from other nerve cells at more than 100 trillion points. Electrical signals race from cell to cell at a rate of 200 times a second, sparking thoughts, memories, actions and feelings. These signals create pathways that transmit 4 billion pieces of information. All of this occurs in the time it takes to blink.

But imagine that the roots of this forest begin to tangle. Gunk begins to build up between the “trees," slowing down electrical activity, causing nerve cells to shrivel and die. It’s easy to picture how a once lively ecosystem would begin to go silent.

This is what happens in the brain of a patient with Alzheimer's disease.

Scientists believe that tangles inside cells (called tau tangles) and the plaque that builds up between them (called amyloid protein) cause the condition that affects 5.5 million Americans, but they still don’t know the exact reasons these changes occur. Nor do they have a concrete way to confirm that this is what’s happening in the brain of a particular patient. (The only way to know for sure if a patient has Alzheimer's is to analyze brain tissue after the patient has died for amyloid protein and tau tangles.) Currently, doctors diagnose patients by ruling out all other possible causes of dementia-like symptoms.

This is why researchers, including several here at Yale Medicine, are looking for ways to diagnose the disease through biomarkers—physical characteristics in blood or tissue samples that are unique to Alzheimer’s patients. Recent research published in the Proceedings of the National Academy of Sciences describes a new technique called vibrational spectroscopy that shows great promise. Vibrational spectroscopy uses reflection of light off a diamond core as a way to visually confirm specific characteristics within blood plasma that are typical for people with Alzheimer’s. The researchers reported that diagnosis using this technique was 90 percent accurate when compared against standard clinical diagnosis (which involves a combination of taking patient history, physical and neurological testing, brain imaging, etc.). This provides a more concrete way to confirm a doctor’s diagnosis, but further research needs to be done to compare the spectroscopy results with brain autopsies.

Even more promising, this method was able to differentiate between blood from an Alzheimer’s patient and one with Lewy Body dementia (LBD). Although LBD is the second leading cause of dementia, it’s often misdiagnosed because the symptoms are so similar to other degenerative brain disorders. “It’s difficult to distinguish between the two clinically,” explains Christopher van Dyck, MD, a psychiatrist at Yale Medicine and director of the Alzheimer’s Disease Research Unit. A misdiagnosis can be dangerous because certain types of medications that are helpful to people with Alzheimer’s can cause severe complications, such as neuroleptic sensitivity, irreversible parkinsonism or neuroleptic malignant syndrome, in patients with LBD. 

Dr. van Dyck’s own research is at the forefront of developing techniques to diagnose Alzheimer’s through biomarkers. His team partnered with the PET imaging center at Yale Medicine’s radiology department to use neuroimaging to detect the amyloid protein and tau tangles that are characteristic in the brains of Alzheimer’s patients. The amyloid part of the technique was approved by the FDA in 2012. Since then, it has revolutionized clinical research. While a positive scan showing amyloid protein doesn’t necessarily mean that a patient has Alzheimer’s, a negative scan definitively shows that the patient does not have Alzheimer’s. Now, many patients who want to enroll in clinical trials for Alzheimer’s medication are required to have a positive result from an amyloid PET scan first.  

Richard E. Carson, PhD Ming-Kai Chen, MD, PhD Sam Massaro (Research Assistant Scheduler – fake patient) Brenda Breault RN, BSN

The PET center at Yale Medicine scans patients for amyloid protein to detect Alzheimer’s. The PET team, including Richard Carson, PhD and Ming-Kai Chen, MD, PhD (pictured here), are collaborating with Dr. van Dyck to develop a novel way to scan for synaptic density in Alzheimer’s patients. This technique will be useful for determining whether or not a particular medication has the potential to reverse brain damage from the condition. 

Credit: Robert A. Lisak

The PET scan technique has also allowed doctors to diagnose the disease earlier than previously possible. The earlier the diagnosis of Alzheimer's disease is made, the earlier doctors can prescribe medications, such as cholinesterase inhibitors, which work best on patients with mild to moderate Alzheimer’s. These drugs can help delay or prevent symptoms from getting worse by preventing the brain from breaking down a chemical called acetylcholine, which plays an important role in memory. “Alzheimer’s causes progressive, irreversible brain damage. The earlier you catch it, the more effective our interventions will be,” says Dr. van Dyck.

When it comes to the complex and vibrant ecosystem within our brains, every second matters.

Resources for Alzheimer's Patients at Yale Medicine

Founded in 1981, Yale Medicine’s Dorothy Adler Geriatric Center is one of the oldest and most comprehensive geriatric assessment programs in the United States. The Adler Center is directed by Richard Marottoli, MD and provides evaluation and care of hundreds of patients with Alzheimer's disease annually. In addition, the center's Memory Clinic is led by Steven Strittmatter, MD, a neurologist at Yale Medicine who treats people with varying types of dementia. The clinic offers comprehensive support from both neurologists and neuropsychologists (clinicians who have expertise in the relationship between the brain and behavior) and connects families to support groups and services. New patients can expect to spend an hour and a half at the clinic. 

To schedule an appointment with the Geriatric Assessment Center, call 203-688-6361

To schedule an appointment with the Neurology Memory Clinic, call 203-785-4085