Frontotemporal Dementia (FTD): A disabling disease with some promise for the future
Scientist Explains with Dr. Nico Paulo Dimal
What is FTD?
FTD is the umbrella term for a group of progressive brain diseases that cause significant loss of function primarily through changes in behaviour, personality, and language skills. FTD is nearly as common as Alzheimer disease as a cause of dementia symptoms before age 65. Symptoms can start as early as 30 to as late as 80 years of age.
Although there is no cure for FTD at present, there is ongoing research into causes, diagnostics, and treatment modalities, some of which are showing exciting promise.
What causes FTD?
FTD is caused by an abnormal buildup of proteins in specific parts of the brain responsible for thinking and behaviour. The most common abnormal proteins are called tau and TDP-43. When these proteins accumulate, they cause death of neurons and supporting cells that then leads to shrinkage of those areas, which is termed neurodegeneration. When these changes are identified under the microscope at autopsy, the pathologic diagnosis of frontotemporal lobar degeneration is made. 20-40% of FTD cases can be from an inherited cause or a genetic mutation.
What are the types and the symptoms of FTD?
There are three main types of FTD, one of which is behavioral variant FTD (bvFTD).
The most important symptom of bvFTD is a change in personality; this happens particularly during the first 2-3 years of the disease. Changes in personality include disinhibition or loss of one’s ability to control impulses and maintain social appropriateness. Another symptom is apathy wherein one gradually loses motivation and interest in one’s activities or hobbies. Others lose the capacity to be empathetic or have abnormally increased appetites. People with bvFTD can develop obsessions and rituals. Lastly, decision-making capacity and concentration skills also decline.
The other two types of FTD cause a decline particularly in communication skills. For example, in nonfluent FTD, one develops increasing difficulty pronouncing words and stringing sentences together. In semantic variant FTD, one may slowly lose vocabulary and knowledge of the world and struggle with understanding what other people say. All these types of FTD have one thing in common—these changes in linguistic skills and personality significantly impair one’s day to day activities.
How is FTD diagnosed?
Clinicians will gather information about changes in thinking, behaviour, and function from the patient and the family. Importantly, thorough physical and cognitive examinations are performed. It is essential to have brain imaging done, which often shows signs of shrinkage in the frontal and temporal lobes. Aside from routine blood work, genetic testing is often performed to check for a possible inherited mutation as a cause.
How is FTD treated today?
There is currently no Health Canada-approved treatment for FTD. Clinicians often take a symptomatic approach to management—they target various symptoms of FTD through non-pharmacological strategies or with medications directed towards disabling symptoms.
What are some potential new treatments for FTD?
Potential treatments for FTD aim to alter the course of the disease (disease-modifying treatment) or target cognitive and neuropsychiatric symptoms. Therapies for disease modification are being explored in those with genetic mutation carriers in the progranulin (GRN) or the C9orf72 genes. One investigational drug is a monoclonal antibody which targets the sortilin protein in the brain. The objective is to increase progranulin levels as a potential strategy to address neurodegeneration. Other studies employ gene therapy using viral vectors that transport a functional GRN gene into the brain.
Treatment modalities that target malfunctioning brain circuitry using brain stimulation are also being studied. These aim to enhance cognition or treat behavioral symptoms of FTD by modulating or stimulating dysfunctional neural circuits. Brain stimulation can be done through noninvasive techniques that deliver weak electrical currents (transcranial direct current stimulation) or magnetic pulses (repetitive transcranial magnetic stimulation) applied to the scalp. Conversely, electrodes can be implanted surgically in specific areas through a procedure called deep brain stimulation (DBS). DBS has been proven effective and is Health Canada-approved for other neurological diseases such as Parkinson disease, epilepsy, and essential tremor.
The FRONTSTIM trial, with co-principal investigators, Drs. Andres M. Lozano and Carmela Tartaglia, is investigating the role of DBS in addressing apathy, one of the symptoms of FTD and other dementias. This trial and others like it are providing much-needed hope for this debilitating disease.
