Rapidly developing molecular research has given clinicians more insight into frontotemporal lobar degeneration (FTLD), an umbrella term for a group of neurodegenerative conditions characterized by progressive degeneration of the frontal and anterior temporal lobes of the brain. Both behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) are clinical dementia syndromes caused by FTLD.

Speech-language pathologists are deeply involved in the treatment of this patient population. Patients with FTLD require tailored, comprehensive evaluations to account for the variability of the condition and its subtypes.

Treatment efficacy research in FTLD is still in its infancy. "Right now researchers are just trying to figure out what the molecules are that make up the cellular pathology," said Sandra Weintraub, PhD, clinical core director of the Cognitive Neurology and Alzheimer's Disease Center at Northwestern University Feinberg School of Medicine in Chicago, IL. "In Alzheimer's we know our targets are plaques and tangles, but we don't know what our drug targets would be in the neuropathology that causes PPA and bvFTD. That's a big part of the puzzle."

PPA and bvFTD present with very different sets of symptoms. Patients with bvFTD generally present with behavioral and personality changes caused by damage to the areas of the prefrontal cortex linked to social cognition. Such changes can include lack of empathy or inappropriate social behavior.

PPA initially affects the language cortex but not necessarily memory. In patients with clinical symptoms, "episodic memory is intact in the early stages, before the pathology spreads to affect other brain regions," Dr. Weintraub said. "They start having difficulty with word finding and make errors in speech."

While researchers have a general idea of the symptoms associated with PPA and bvFTD, definitive diagnostic tests do not yet exist, aside from a brain autopsy. Blood tests and magnetic resonance imaging (MRI) scans cannot determine the cause of degenerative brain damage at a microscopic level. "Even when you make these diagnoses and follow the individuals to death, in most cases the underlying pathology is some kind of FTLD, but in some cases we find Alzheimer's pathology," she said.

Scientists have identified close to 15 types of degenerations, and new proteins and molecules related to FTD are discovered daily, she noted. To further complicate matters some patients with bvFTD and PPA clinically "have Alzheimer changes in their brain."

Researchers are working to define FTD targets and differentiate them from the neurofibrillary tangles and senile neuritic plaques of Alzheimer's disease. Brains affected by PPA and bvFTD have distortions of tau and amyloid protein similar to Alzheimer's but with different molecular abnormalities. "There is a subgroup of FTLD that is caused by an abnormality of the tau protein but different than what you see in Alzheimer's. Pick's disease is an example of a 'tauopathy,'" she explained.

Northwestern researchers were among a group that reported a genetic mutation in the progranulin gene associated with some forms of FTD in 2006. The following year they and colleagues at the Mayo Clinic described two families with several individuals affected by PPA due to a mutation in the progranulin gene. Most PPA cases are not inherited (i.e. familial), but these cases helped show a link to a gene known to cause forms of FTLD.

Research into primary progressive aphasia has focused on the identification and definition of severe language deficits associated with the condition. "The field of PPA is trying to subtype these language deficits because we believe they are all associated with different patterns of atrophy and might be informative on a neuropathological level," Dr. Weintraub said.

She was part of a group of researchers last year that found an association between agrammatism and tauopathy in brain autopsies of patients with PPA. "We thought a clinical sign of grammatical processing deficits may increase the suspicion that you are dealing with a tauopathy rather than something else, so we are trying to identify clinical markers that could increase our level of successfully predicting what we are going to find in the brain," she said.

That research led to the development of the Northwestern Anagram Test, which assesses grammatical processing abilities. Northwestern researchers now are developing a method to relate clinical language deficits to atrophy patterns on volumetric MRI, she said. "We are looking at evoked potential responses to words in people with PPA, trying to attack the problem from a molecular to a clinical, electrophysiological and structural level."

Dr. Weintraub also is involved in broader research on the differences in clinical features between patients with Alzheimer's and those with FTD to get a more complete picture of each pathology. "We are going to learn a lot about dementia and how to help people as well as how the brain works," she said.

"FTD encompasses several variants that affect speech, language and behavior differently," said Daisy Sapolsky, MS, CCC-SLP, of the FTD Unit and Department of Speech, Language and Swallowing Disorders at Massachusetts General Hospital in Boston, MA. "Even within these variants, patients are heterogeneous and can present differently in terms of their receptive and expressive language skills, rate of decline, and psychosocial factors. Relying on knowledge of general characteristics of the disorder as a whole can be insufficient to help an individual patient."

An evaluation identifies strengths that can be capitalized on in treatment. Therapy at MGH centers around teaching patients and families compensatory strategies designed to optimize function and reduce frustration. "We focus on compensation rather than on rehabilitation or reversal of the aphasia, as this is a progressive disorder," Sapolsky said.

Patient and family education is a major part of treatment. Patients may see media accounts of stroke survivors overcoming aphasia and wonder why they do not see similar improvement. Understanding and involvement by family members and caregivers are crucial, especially in preparing for future decline and making use of strategies on a daily basis, noted Sapolsky, who said therapy is a 50-50 endeavor between the patient and caregiver. "The job of implementing these communication strategies often can fall more heavily on the partner than the patient."

Preparing for future decline is a delicate matter that should include a discussion about the difference between aphasia from stroke versus from a progressive disorder and what patients should expect in terms of deficits. Encourage them to implement compensatory strategies as early as possible. Sapolsky typically tells a patient, "Even if we don't need to use these strategies for quite a few years, it will help us down the road to introduce them now."

Some patients are receptive to early implementation, while others are reluctant to think about what may lie ahead. "Use your clinical judgment as to when you should push a little bit and when you should back off," she advised. "Give them time to adjust to the diagnosis."

Generally, she begins therapy by employing strategies that address word-finding difficulties, a common problem in many patients. Patients and caregivers learn strategies such as semantic and phonemic cueing and the use of pictures. Whether the patient provides the target word, a successful circumlocution, or points to a picture, the goal is to facilitate expression in any way that works.

"The partner can prompt the patient to use any modality they can think of if they can't say the word," Sapolsky explained. "Can they describe the concept, draw it, or gesture? Can the partner ask yes-or-no questions until they can guess what the word or thought is?"

A strategy may be simple, such as slowing down speech and allowing for natural pauses within the flow of conversation. "Society often is rushed, and people speak very quickly," she said. "Patients feel pressured to think of a word, and a cycle can start of getting frustrated, feeling rushed, and not being able to think of the word. It is helpful to allow for some pauses to relax and give the patient time."

Other strategies include using multiple choice questions with patients, such as "Do you want to go to the movies or to the supermarket?" Caregivers can write down options so patients with severe word-retrieval problems can point to their choice. A communication picture book created by the patient, caregiver and speech-language pathologist can use words, pictures or a combination as an effective conversation tool.

Outpatient speech-language therapy at MGH typically is provided in hour-long sessions over a six- to eight-week period. The speech-language pathologist asks patients and communication partners to return for follow-up visits.

Patients who complete individual therapy may participate in group therapy, in which patients and families practice therapy strategies in a safe environment. "They can share tips and strategies," Sapolsky said. "It's often beneficial just to meet other people going through the same thing."

She stressed the importance of speech-language pathologists educating others about FTD, not only the family but related professionals who may not be aware of it.

Patient empathy and sensitivity are paramount, she said. "By the time patients come to our door, they can be very distressed. It may have been a long road to get the correct diagnosis and to find a health care team that is knowledgeable about FTD. They have gone through a lot already, so it's important to be sensitive to that."

For More Information

• Daisy Sapolsky, dsapolsky@partners.org, online: www.ftd-boston.org

• Sandra Weintraub, sweintraub@northwestern.edu, online: www.brain.northwestern.edu/ppa

Alyssa Banotai is a Senior Associate Editor at ADVANCE. She can be reached at abanotai@advanceweb.com.