June 2, 2022/Geriatrics

Behavioral Symptoms in Neurodegenerative Diseases (Podcast)

Cognitive phenotypes are related to behavioral changes in Alzheimer’s and Lewy body dementia


When patients are diagnosed with a neurodegenerative disease such as Alzheimer’s disease or Lewy body dementia, they often ask what kinds of changes they can expect. The question can be difficult for neurologists to answer because a subset of these patients will experience behavioral symptoms during disease progression.

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“Managing behavioral changes is the toughest job I have,” says Jagan Pillai, MD, PhD, a behavioral neurologist in Cleveland Clinic’s Lou Ruvo Center for Brain Health. “So far, we have no way of even understanding which of these people are at high risk for developing behavioral symptoms, which of them are at low risk … and how we, as physicians, can guide them through this process.”

That was Dr. Pillai’s motivation for a recent study that showed the relation between presenting cognitive phenotypes of Alzheimer’s disease and Lewy body dementia and the likelihood of subsequently developing behavioral and psychological symptoms.

In the newest episode of Cleveland Clinic’s Neuro Pathways podcast, Dr. Pillai shares his findings and what they mean for the future of dementia practice and research. He discusses:

  • Risk factors associated with presenting clinical phenotypes
  • The likelihood of behavioral changes in young-onset versus older-onset Alzheimer’s
  • The potential effect of a patient’s sex on behavioral changes
  • How educational level and cognitive reserve impact outcomes for patients with cognitive problems
  • Clinical implications of the study results
  • Follow-up research, including a study examining cognitive circuits involved in hallucinations versus delusions in patients with neurodegenerative diseases

Click the podcast player above to listen to the 18-minute episode now, or read on for a short edited excerpt. Check out more Neuro Pathways episodes at clevelandclinic.org/neuropodcast or wherever you get your podcasts.

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Excerpt from the podcast

Podcast host Glen Stevens, DO, PhD: Take me through a little bit more of the research. If I come to see you, what are my risk factors for figuring out my phenotype and what’s going to happen to me down the road?

Dr. Pillai: The number one thing is localization. We always think about how do you localize the symptoms, and that’s pretty much what is primarily done in this paper. It basically makes the connection that if you localize a problem to a certain part of the brain, then you might have problems — both cognitive and behavioral issues — later in that part of the brain.

Take Alzheimer’s disease, for example. It’s generally thought about as someone having memory problems initially and over a period of time they develop other kinds of symptomatology. So when you have memory problems initially, that means your hippocampus or the medial temporal lobe is involved and then the disease affects other areas.

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What we have found out over a period of time is that this memory onset is only a subset of cases. It is definitely a majority of cases, but we still have a significant number of Alzheimer’s disease cases where the initial symptom may be primarily, say, language related, where patients have aspects of aphasic syndrome or they have problems with judgment where they are not able to take care of themselves or plan what their daily life looks like. Or they may have primarily visuospatial symptoms where they have difficulty navigating or reading.

The key idea that drove this research is that if you have amnestic or memory complaints, it is coming from the medial temporal lobe. If you are having primary executive or judgment problems, it’s likely to involve the frontal lobe. If it’s a language problem, it’s going to involve the left temporal lobe, and if it is a spatial problem, the parietal lobe. If you’re having relatively focal pathology at the outset, it’s also possible that the behavioral symptoms are going to match the same circuits that are being affected in each of those areas. It’s very intuitive, but actually it was never looked into.

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