Recognizing and Managing Alzheimer’s Disease in People With Down Syndrome (Podcast)

Individuals with Down syndrome carry an additional copy of chromosome 21 (trisomy 21), the site where the gene for the amyloid precursor protein lies. This leads to overproduction and accumulation of amyloid protein in the brain, a fundamental pathological process in Alzheimer’s disease (AD).

“As a result, individuals with Down syndrome have a nearly inevitable risk of developing Alzheimer’s disease, with lifetime risk estimates of 90% to 95%,” observes Charles Bernick, MD, MPH, a neurologist specializing in AD at Cleveland Clinic Lou Ruvo Center for Brain Health.

Dr. Bernick notes that diagnosing and managing AD-related cognitive decline presents special challenges in individuals with Down syndrome but that this population also offers unique opportunities to better understand AD. In the latest episode of Cleveland Clinic’s Neuro Pathways podcast, Dr. Bernick explores these challenges and opportunities, along with a range of other issues around AD specifically in the setting of Down syndrome, including:

• The connection between Down syndrome and AD
• Screening and monitoring recommendations
• Diagnostic testing and biomarkers
• Treatment considerations
• Emerging research and clinical trials
• Insights into AD from Down syndrome research

Click the podcast player above to listen to the 25-minute episode now or read on for an edited excerpt of its transcript. Check out more Neuro Pathways episodes at clevelandclinic.org/neuropodcast or wherever you get your podcasts.

This activity has been approved for AMA PRA Category 1 Credit™ and ANCC contact hours. After listening to the podcast, you can claim your credit here.

Excerpt from the podcast

Podcast host Glen Stevens, DO, PhD:Are there modifiers in the Down syndrome population that would affect the age at onset or the progression of the disorder among those who are going to develop Alzheimer's disease?

Charles Bernick, MD, MPH: Yes, there probably are, but on the flip side, there’s a certain predictability, at least biologically, in the progression of the amyloid deposition. So we know that by around the age of 35 and certainly by age 40, accumulation of amyloid is almost inevitable. So you can measure that. And symptoms often will start five to 10 years later, or maybe a little after that. So the onset of symptoms is somewhere in the mid-40s to mid-50s. However, just as in sporadic Alzheimer's disease, there are some individuals who have amyloid present but who seem resilient, at least resilient to developing some of the symptoms or decline that we see clinically. We don’t really understand why that happens. It probably is multifactorial, but certainly there is some heterogeneity in the symptom progression, yet it’s a very predictable disease from a biological standpoint.

Dr. Stevens: I guess then the question is whether Alzheimer’s is underrecognized or undertreated in this population.

Dr. Bernick: I think it is, for a lot of different reasons. One is that Down syndrome patients didn’t used to have the longevity that they do now. There weren’t as many people with the condition living into their 50s or 60s, so people didn’t pay much attention to Alzheimer’s-like symptoms because they weren’t that common. Now it’s different. It’s much more likely that an individual with Down syndrome who has control over their other medical issues will make it into their 60s. So one factor is just this change in the frequency of the disease. I think another factor is that when you have individuals who already have intellectual developmental disability of various levels, the cognitive or functional decline sometimes just gets washed out. If people get older, they figure they’re just getting older and they don’t really think about a secondary process that might be going on.

Dr. Stevens: Let’s say I’m a primary care physician who has some patients in my practice who have Down syndrome. Should I start doing cognitive screening on these patients at some point? Are there recommendations or guidelines?

Dr. Bernick: Yes, there are some general guidelines. One is that probably at least by the age of 40, the person should undergo some baseline assessment of their functional capacity and maybe even their cognitive capacity. There are some batteries that are available for this population. This should be done to get a sense of where they are, starting at about 40 and then subsequently with some type of annual examination. If there is a change, that should lead to further workup that we do for cognitive impairment, which would be looking for other comorbidities that could cause the problem. And now that we have various tools available for the diagnosis of Alzheimer's disease, they can be applied to this population with Down syndrome as well.