Dementia

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Clinical Responses to
Frontotemporal Dementia

by R. D. Harbaugh, MD

 

Frontotemporal dementia (FTD) is the term used to describe a clinically heterogeneous group of patients with frontotemporal dominant neurodegeneration.

 

The FTD syndromes (several clinical and pathogenetic subtypes with shared features) can be characterized primarily as the "behavioral" dementias. The FTD-related clinical syndromes are a leading cause of dementia in patients under the age of 70 years, with the mean age of onset in the sixth decade. FTD is nearly as common as Alzheimer's disease (AD) in dementia patients under the age of 70 years and is more common in patients under the age of 60 years. FTD constitutes approximately 5 percent of all the dementias.

 

The main subtypes of FTD include:

•    a behavioral syndrome called behavioral variant FTD (bvFTD), which is exemplified in our case and which is the most common;
•    a nonfluent / agrammatic (meaning impairment in specific word utilization) variant known as aphasia primary progressive aphasia syndrome (nfavPPA);
•    a semantic variant (meaning impaired comprehension of words) known as primary progressive aphasia syndrome (svPPA).

 

Robert Harbaugh, MD

 


See Case Report below >


These later disorders overlap with a disorder previously known as Pick's disease.

 

These subtypes are connected by very complex clinical and, more importantly, pathological underpinnings, but also share substantial overlaps which, in reality, create a continuum of disease expression, especially as the disorders unfold over time.

 

This article will focus upon the behavioral variant. This area of clinical neuroscience is among the most complicated and dynamic arenas in all of neuroscience.

 

Symptoms and Etiology

The frontal lobes in Homo sapiens act to create truly advanced "social" animals; they shape goal-directed behaviors, motivation and our innate awareness of ourselves and those around us. The first symptoms in bvFTD are variable although most patients show dramatic changes in executive control (planning / executing adaptive behaviors) or personality.

 

Characteristic behaviors are an acquired change in social interactions, which tend to exclude the well being of those around the affected person (manifested as indifference, lack of concern and/or loss of insight).

 

Antisocial behaviors-including theft, reckless driving, and indecent exposure-can lead the FTD patient to be arrested. Some patients become socially withdrawn, leading to a misdiagnosis of depression. Apathy, overeating, disinhibition, hypersexuality and repetitive compulsive behaviors are common early features driven by degeneration of specific areas of the brain which modulate these activities. Ad- diction-related behaviors-including alcoholism, suicide, schizophrenia, sociopathy and bipolar disorder-are common initial diagnoses for individuals with FTD.

 

The bvFTDs are among the most challenging, and to a certain extent, devastating degenerative disorders seen on a routine basis by specialists. Many patients with bvFTD are considered initially to have purely psychiatric disorders, as basic cognitive skills may be well preserved in the first few years. Some individuals tragically end up within the legal system (e.g. incarceration) due to socially unacceptable behaviors. Other domains of the mind, such as cognitive capacities (e.g. language, memory, visuospatial functioning, etc.), invariably become impaired as the disorder progresses.

 

Diagnosis and Treatment

In experienced hands, characteristic bvFTD is readily diagnosed by routine clinical methods, including detailed neuropsychological testing. As the disorder progresses, brain imaging demonstrates the expected loss of tissue in the affected regions. Genetic testing is available on a research basis. Unfortunately, as with all the primary de- generative dementias, no disease-modifying interventions have been developed to date. However, a select number of medications (in particular the SSRI-class agents) can modulate unacceptable behaviors.

 

The FTD group of disorders, although uncommon and not a major health problem numerically in relationship to AD and other more common forms of dementia, have created a rapidly evolving scientific test-bed for understanding the basis of acquired brain degeneration. Researchers have now discovered that related (connected) brain circuits appear to "degenerate" in concert. The same processes we see in normal early brain development demonstrate a reverse process or "unraveling" due to the accumulation of misfolded, native structural or signaling proteins within specific nerve cells.

 

It now appears that all the common dementias share this property. Thus, developments in one research arena will undoubtedly impact another. In a quiet way, the very complex arena of the FTDs may unlock keys to combating the impending tsunami of dementias, which will inevitably descend upon our long-living human populations. From a basic research standpoint, understanding the most unique and complex part of our own legacy, the frontal lobes, remains a rewarding endeavor in itself.

  

Case Report: Frontotemporal Dementia

 

A 58-year-old, right-handed, white, married father of two, a disabled CPA, was evaluated neurologically for a 2.5-year history of progressive acquired behavioral and personality changes.

 

The patient describes no family history of significant neurological disorders. He was in his usual state of good health until approximately 2 years prior to his first medical contact, when co-workers approached his family about subtle but progressive changes involving his work-related aberrant behaviors. Whereas he had always been "detail-oriented," he was making careless errors, leading to client complaints about sloppy work. When confronted about these observations, the patient simply ignored the requests, making uncharacteristic profane statements.

 

Whereas he had been a devoted family man who participated in his local church, he now became disinterested in family and friends, spending time watching television and becoming entranced with simple household items (e.g. would pick up a spoon and manipulate it for long periods of time).

 

He was arrested for shoplifting and placed upon administrative leave by his employer. When confronted, the patient simply shrugged his shoulders and seemed to express a profound lack of concern, behavior in direct contrast to his lifelong personality style of compliance with social norms (his friends and family commented that this was "totally out of character").

 

His wife sought counseling and forced her spouse to see a mental health specialist. Several antidepressants had no effect upon his state of being and functionality. Finally, when he was found to be compulsively putting objects into his mouth, his physicians recognized the possibility of a neurological disorder.

 

When seen neurologically, the patient was unkempt, distracted and poorly cooperative (disinterested). The basic neurologic / physical exam was otherwise unremarkable. With vigorous coaching, he was able to complete essential elements of a bedside mental status exam without signs of major cognitive impairment. Of interest, his teenage son had first expressed concern that "maybe something is wrong with Dad's brain." The patient and family denied any other systemic or neurologic symptoms of consequence, and the patient was on no medications when first seen.

 

Neuropsychological testing confirmed definite impairment in frontal lobe functioning, with suggestions of mild language impairment (difficulty comprehending complex sentences and naming objects). MRI brain scan was unremarkable with the exception of mild but distinct atrophy for age of the lateral aspects of both frontal lobes, symmetrically. Brain PET scanning confirmed the presence of relative bifrontal hypometabolism.

 

Having met the accepted criteria for diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), the patient was placed on permanent medical disability and has moved into a residential care facility where high-dose selective serotonin-reuptake inhibitor (SSRI) treatment has markedly lessened his socially inappropriate behaviors (e.g. grabbing others, incessant profanity and resistance to care). He is being referred to a tertiary care center for further study and genotyping at the request of his family and medical professionals.

 

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