Recent News of Bruce Willis’s Frontotemporal Dementia Diagnosis Raises Questions About Available Treatments

Recent News of Bruce Willis’s Frontotemporal Dementia Diagnosis Raises Questions About Available Treatments

Frontotemporal Dementia (FTD) is a neurodegenerative disease that affects two brain structures:  the frontal lobes and the temporal lobes. The location of damage is distinct from that of Alzheimer’s Disease (AD), which is characterized by the degeneration of the brain structure known as the hippocampus. For each of these conditions, neurodegeneration can be readily quantified by the amount of shrinkage (loss of tissue) in these structures, which can be observed through MRI or PET imaging. 

Pure FTD is most frequently seen in individuals between the ages of 50 and 60, if not earlier, whereas AD is generally seen after age 65.  However, degeneration of multiple brain structures can occur at the same time, resulting in simultaneous symptoms for some patients.

The symptoms of FTD fall into two broad categories:  1) the speech variant, which manifests as language problems — typically, difficulty forming words and phrases; and 2) the behavior variant, where someone loses the behavioral guards that form part of their normal personality.  Examples of the behavior variant include apathy, a lack of caring about others, and an inability to distinguish between right and wrong.  These two variants can occur at the same time, to varying degrees.

FTD can have a genetic accelerant, much as AD does.  The arrival and progression of AD are accelerated by the status of the ApoE gene; FTD is commonly accelerated by inherited mutations of the GRN and PGRN genes, as well as a run of “letters” known as “C9orf72” (Chromosome 9 open reading frame 72).

As with AD, the symptoms – and progression – of FTD can be masked or exacerbated by numerous comorbidities. These can include thyroid disorders, anemias and nutrient deficiencies, sleep apnea and sleep disorders, inflammation and infections, lack of exercise and mobility, cardiovascular diseases, kidney and liver disease, hearing loss, depression, and drug burden. Many of these are readily treatable, and the combination of those treatments can unmask the root problems, as well as slow the progression of the neurodegeneration.

Looking specifically at drug burden: FTD is accelerated by medications with a high anticholinergic cognitive burden (ACB), as is AD. Nephrotoxic drugs exacerbate the progression of kidney disease, so these drugs should be carefully managed. Similarly, patient and provider should carefully manage medications that induce or exacerbate heart disease, sleep problems, liver disease, and hearing loss.  A high opioid load is frequently seen in those who are concomitantly dealing with chronic pain and neurodegeneration. Opioids can also accelerate overall neurodegeneration. Polypharmacy often results in dozens or even hundreds of clinically-significant drug-to-drug interactions (DDIs), which can “scramble” someone’s neurological and behavioral status.

Management of FTD thus resembles potentially effective care for AD.