Frontotemporal Dementia and Aphasia: Celebrity Diagnoses and Misconceptions

In February 2023, American actor Bruce Willis disclosed his official diagnosis of frontotemporal dementia at age 67.¹ The following year, American television talk show host Wendy Williams revealed her same diagnosis at age 59.² Both public figures’ diagnoses have brought renewed attention to the rare neurodegenerative disease due to obvious changes to their language, behavior, and speech.

Frontotemporal dementia, also referred to as Pick Disease, presents with neuronal damage to the brain’s frontal and temporal lobes. It is unusual in that it is diagnosed at an earlier age of 65 and younger. Aphasia is a hallmark symptom of frontotemporal dementia and is identifiable by the immense impact it has on a patient’s behavioral and emotional capabilities.³

To delve deeper into frontotemporal dementia, a neurodegenerative disease state that is distinct from the more familiar Alzheimer disease (AD), we interviewed Henry Paulson, MD, PhD, a neurology professor and director of the Alzheimer Center at the University of Michigan Medical School.

Dr Paulson studied movement disorders and neurogenetics at the University of Pennsylvania Health System, specializing in AD and frontotemporal dementia. He has also conducted research at the Paulson Laboratory, examining mechanisms of frontotemporal dementia, and has treated patients dealing with a variety of cognitive disorders, including different types of dementia.

In his interview, Dr Paulson shares insights into common misconceptions of frontotemporal dementia, as well as challenges that physicians face in the field. He also explains differential diagnosis, etiologies, and rare presentations of frontotemporal dementia, as well as recent work conducted at his laboratory.

What are some common misconceptions you’ve heard or read regarding frontotemporal dementia?

Dr Paulson: Many people don’t have any misconceptions about the disease; they just don’t know anything about it at all. When someone of prominence — a celebrity or an actor — develops a condition, then people say, “what is that?” They’ve never heard of it and very little is known by many people. Even though it’s always sad when someone develops frontotemporal dementia, it is good when more people are aware of the condition. 

A common misconception I see in the clinic is when people say, ‘Doctor, the good news is I don’t have AD, I just have dementia.’ Well, some dementias are not as good as AD. I would say, in general, frontotemporal dementia tends to be earlier onset, tends to have a faster rate of progression, and often has more disabling symptoms. So, although some people may consider dementia a ‘good’ neurologic disorder, relative to others, frontotemporal dementia can, in some ways, be more tragic than AD.

A couple of years ago, when they announced that Bruce Willis had primary progressive aphasia, those of us who study dementia knew exactly what that meant. It was described in literature that he has a language problem. And all of us knew that meant he had frontotemporal dementia, which can take different flavors. But, one of the most common flavors is, in fact, progressive language disturbance. And that was his first presentation.

I think sometimes physicians are more comfortable telling a patient that they have aphasia, rather than saying, ‘you have dementia.’ In fact, someone could have aphasia before they’ve met the clinical criteria for dementia. So, it is a precise thing to say, ‘you have primary progressive aphasia,’ if you’re having language disturbances that are progressive and intrinsic to the brain. And, one may not have signs of frank dementia at that point in time.

What is the differential diagnosis of frontotemporal dementia? What are some challenges neurologists may experience when diagnosing the disease?

Dr Paulson: Frontotemporal dementia can have a lot of mimics. If someone has a frontal lobe tumor, it can manifest with progressive symptoms that look like frontotemporal dementia. Sometimes AD manifests as a frontal variant form and people express profound behavioral issues. That is a frontal variant of AD. You would not know that unless you actually did biomarker testing for AD. 

There are different forms of primary progressive aphasia. One of those forms is the logopenic variant. The logopenic variant is a form of progressive language disservice that is more often due to an AD process than it is to the classic frontotemporal dementia processes.

What are some uncommon or rare presentations and symptoms of frontotemporal dementia that make it challenging to diagnose?

Dr. Paulson: I think it can be challenging even for the expert to diagnose because a condition like frontotemporal dementia, which has different clinical phenotypes, has to start with something; and that something can be a fairly subtle symptom. In particular, behavioral variant frontotemporal dementia, often also called Pick disease, manifests with behavioral and psychiatric disturbances that might easily be interpreted as a psychiatric disorder, as opposed to a degenerative brain process. 

Moreover, the frontal lobe is a fairly large part of our brain, which is incredibly important for controlling our emotions, inhibitions, decision-making, as well as planning. There can be fairly subtle changes to the brain in terms of circuits that are affected that can lead to profound behavioral changes without seeing a whole lot during brain imaging. That can be a little difficult at times.

For a couple of years at minimum, the pathology of any dementia is occurring before any symptoms manifest. Certainly, in AD, that’s probably a decade of accumulation of amyloid before you see many symptoms. In the case of the frontotemporal dementias, it’s a shorter period of time; however, I would say when families show up to the doctor due to a troubling symptom, it’s already a couple of years into the course of the disease.

Can you walk us through possible etiologies for early vs late onset frontotemporal dementia? Are there any biomarkers, patient or family histories, genetics that are correlated with early onset frontotemporal dementia, or early onset dementia more generally?

Dr Paulson: In a way, I think that it’s good to consider frontotemporal dementia as both a genetic and environmental condition with a little more of a genetic flavor to it than AD. AD clearly has an underlying genetic component. Most AD is not strictly genetic, but there are genetic factors that contribute to its development. In the case of frontotemporal dementia, the genetic load is even greater. The disease tends to occur earlier. Instead of being diagnosed at age 68 or 75, it’s more likely to be diagnosed at age 58 or 60. 

In those families that have a clearly inherited form of frontotemporal dementia, it can even be a little bit earlier. Those inherited forms of frontotemporal dementia tend to be dominantly inherited, running from generation to generation. An individual who inherits the mutated gene will develop frontotemporal dementia within their lifetime, if they live to age 70 or 75. In general, the hereditary forms of frontotemporal dementia, which comprise at least one-third of frontotemporal dementia cases, tend to develop a little bit earlier than sporadic forms of the disease.

Can you share any exciting research or projects on which you’re working? Are there any studies you or your colleagues have published that you feel have made an impact in this space?

Dr Paulson: One of the most important proteins that underlies frontotemporal dementia is TDP43. While there are a couple of major proteins implicated in frontotemporal dementia, 2 of those are tau and TDP43, which also occur in AD. At my center, our brain bank director, Sami Barmada, MD, PhD, has done some beautiful work identifying genes that can regulate the toxicity of TDP43. That has not led to a therapy yet, but I think it could lead to one down the road. 

I think that it’s also a very exciting time in the world of frontotemporal dementia. For reasons we don’t fully yet understand, the genetics of frontotemporal dementia are shared with the genetics of amyotrophic lateral sclerosis (ALS). They’re all on a spectrum. Some disease genes, such as C9orf72 repeat expansion, are the most common cause of multiple disease states, including ALS and frontotemporal dementia.

Historically, we have thought of the 2 as completely separate diseases, but now we recognize they are part of the same group of disorders. Because we know that mutation is a repeat expansion, there are many groups that are working on ways to reduce the levels of that toxic gene product. And while we don’t have a therapy yet, we have our fingers crossed.

I think it’s a good time for research in frontotemporal dementia disorders. Most of the AD centers in the country have focused on AD, but now there are several major centers that are really leading the way toward understanding the causes and treatments for frontotemporal dementia. Our center is among those, and we’ll just keep pushing.

Editor’s note: Some responses have been revised for clarity and brevity.