Building on Advancements in Alzheimer Disease Diagnostic Methods

Jonathan Graff-Radford, MD

As our understanding of the various Alzheimer disease-related pathologies grows, so does the promise of being able to utilize new biomarkers for diagnosis and possible prevention efforts. The ability to diagnose at-risk patients earlier in the disease process may be the missing link to getting a step ahead of treatment, as well as employ risk-mitigating practices.

Jonathan Graff-Radford, MD, a neurologist at Mayo Clinic, is among many in the field who are ecstatic with the most recent progress made. In a year that has shown so much promise, Graff-Radford singled out blood tests as the most notable clinical accomplishment the community has made, adding that the potential use for them will only grow. Blood tests are simple, noninvasive, and present a much more accessible route to screening than other measures currently used, including lumbar punctures.

Despite these developing diagnostic innovations, differentiating AD from other dementias and cognitive impairment remains a concern. Graff-Radford, sat down with NeurologyLive to discuss challenges in diagnosing AD, innovative tactics, and what the next steps are going forward.

NeurologyLive: Can you discuss the importance of World Alzheimer’s Day and what raising awareness for the disease can do?

Jonathan Graff-Radford, MD: World Alzheimer’s Day is really important because it allows us to bring to light the fact that there’s over 5 million Americans with AD over the age of 65. Something people may not know is that there’s actually almost a quarter of a million Americans with AD under 65. This isn’t just a disease affecting the elderly. There’s actually a group of young onset cases as well. It’s the 6th leading cause of death in the US and if we don’t find treatments for, by 2050, we estimate that they’ll be about 14 million people with AD. This really allows us to bring awareness to this public health problem and dementia in general. In fact, there’s a lot we can do as a society and community to work towards lowering dementia rates worldwide. There was an important Lancet paper published this year that identified 12 risk factors for dementia. If we can target those risk factors, they estimated that we can delay or prevent dementia in as many as 40% of cases. These include risk factors such as high blood pressure, diabetes, obesity, physical inactivity, and societal problems including air pollution, which was a new risk factor. For those reasons, it’s really an important day to bring everyone’s attention to.

What are some of the challenges in diagnosing AD?

First, it’s really important to get an accurate diagnosis. When we see people for cognitive impairment in the clinic, there’s a lot of mimics to AD that need to be evaluated for. For example, sleep apnea, vitamin deficiencies, and thyroid problems can all cause cognitive issues that can look a little bit like AD, but instead are reversible. It is important to get an accurate diagnosis because it allows people to be treated at an earlier stage. Additionally, it allows patients and families with AD to get appropriate support and education on the disease so they can plan for the future.

Are there any new diagnostic tools you feel are promising and can be applied in the future?

Over the last decade we’ve really developed biomarkers that can measure the toxic proteins that cause AD amyloid and tau, both in the spinal fluid and then in the brain. Over the last few years there’s been some promising work on blood tests for AD. These blood tests are less invasive, less expensive ways to measure these toxic proteins. They could potentially be used the same way a cholesterol test is used to determine someone’s cardiovascular risk. Essentially, you can get this blood test to determine your risk for AD. They could also be used to screen people for clinical trials in a less expensive and invasive way. I think these are really promising diagnostic tests that are potentially coming on the horizon in the next couple of years.

Among the notable clinical events within the AD community this year, was there anything specific that stuck out to you?

I would echo the fact that everyone in the field is very excited for the blood tests. It has been something we’ve been waiting for because the current biomarker tests are only available at a limited number of centers. Patient’s often don’t want to undergo a lumbar puncture, but a blood test is something that people are really used to from a screening perspective. It really will be a game changer when it becomes available. That’s really the thing we’re most excited about and eager to see more of in the next meeting.

Can you discuss the progress that AD has made over the past decade and where we could be going next?

The progress we’ve made in biomarkers of amyloid and tau in the brain have provided key insights. One of those is that the pathologic processes that lead to AD start 20 years before the first symptom develops. Which correlates to where the field is moving, which is earlier treatment. Because we can identify people who have these proteins in their brain before they develop symptoms, we can then enroll them into trials to try to prevent the buildup of these proteins and hopefully downstream cognitive consequences through the early enrollment. The other area I see the field moving is into treating multiple pathologies at the same time. What I mean by that is, as we’ve learned from people’s donated brains is that they often have more than just AD changes in their brain. They may have vascular changes as well. I see clinical trials starting to target not just AD, but also Alzheimer’s in vascular disease or whatever pathology that person may have as well. It is sort of a cocktail approach to therapy.

One of the things we want to convey to our patients and families is that there is hope for AD. Even though we’ve had a run of negative trials, the research has moved leaps and bounds over the past few years and we’re optimistic that there will be treatments available on the horizon in the not too distant future.

Transcript edited for clarity.