Frontotemporal Dementia and the Importance of Accurate Diagnosis

Relatively speaking, of the major leading causes of dementia out there, there is one that has one of the most mercurial of histories in terms of its respective nosology: frontotemporal dementia (FTD). Depending on what variant one is referring to, FTD is variously referred to as “frontotemporal lobar dementia,” “Pick’s Disease,” “sementic dementia,” and “progressive nonfluent aphasia.” Originally called “Picks Disease” (first described by Arnold Pick in 1892) it was originally described as a syndrome characterized by “amnestic aphasia,” a focal pattern of atrophy involving the temporal and frontal lobes of the brain, and the presence of Pick “inclusion bodies,” and accompanied by a characteristic pattern of language impairment.

Depending on the sources you consult, FTD is either the second or third leading cause of dementia worldwide (with dementia of the Alzheimer’s type and vascular dementia taking up the other of the top three slots). Either way, it seems to be a disease that’s most frequently misdiagnosed. Probably this is because when Arnold Pick identified the first cases of FTD he thought it was necessary to identify these agyrophobic inclusion bodies (Pick bodies) on postmortem in order to positively diagnose FTD (of course, now it’s know that this is not the case).

Dementia in general has been traditionally seen as a disease characterized by cognitive loss leading to significant functional loss. However, there is significant heterogeneity in presentation across dementias. In the case of Alzheimer’s disease, memory dysfunction tends to be the earliest and most central complaint. In the case of vascular dementia, gait disturbance, falls, and a “vascular depression” phenomenon may be leading-edge symptoms.

FTD presents differently. One thing to get out of the way is that FTD is not actually a single disease entity – there are actually two sub-variants, first, probably representing the form noted by Arnold Pick is so-called semantic dementia, where a progressive breakdown in semantic knowledge is evidenced in speech and testing, accompanied by a fluent aphasia (often those suffering from this disorder will be able to easily speak, but it sounds nonsensical at times). Interestingly, in the case of semantic dementia (unlike Alzheimers or vascular dementia), episodic memory is well-preserved well into the progression of the disease.

The second sub-variant of FTD is the behavioral variant (bvFTD), which, as you might expect, has a relatively dramatic presentation. Its presentation often takes the form of rather dramatic personality changes. Early symptoms might include mood lability (e.g, anger outbursts), restlessness, and apathy. As the disease progresses, patients lose insight into their deficits, withdraw socially, and may start exhibiting distressing behavior like impulsiveness (often sexual in nature). Criminal behavior is sometimes reported. Another symptom seen prominently in bvFTD sufferers is hyperphagia, where sufferers will uncharacteristically gravitate towards eating large amounts of food, often carbohydrate-laden. Frontal release signs are seen on neurological exam, such as the palmomental reflex (which is something normally seen in newborns).

One of the issues that comes up when I talk about assessment is the question of, “why does it matter”? In other words, I’ve heard it argued (often from family members and occasionally from physicians) that differentiating, say, differential diagnosis of Alzheimer’s from an FTD variant is largely an academic exercise. Dementia is dementia and really all family members and primary care physicians tend to be interested in is how to manage the diversity of behavioral symptoms that come with any dementia.

I think it does matter. In my practice as a geropsychologist I’ve seen more than a handful of cases of dementia that I was reasonably certain were in fact FTD. A case I recall in particular was of a lady whom I assessed, who was at that time living in an assisted living facility in San Francisco. She was in her late 60s and had been diagnosed with Alzheimer’s disease and her family had approached the Institute on Aging to give her a comprehensive examination. One of the issues that was particularly worrisome for her was this woman’s apathy, she was reported by her family to be sleeping “a lot,” she seemed disinterested in activities, and her neuropsychological testing profile indicated severe impairment in executive functioning. On interview, she presented with a prominently “flat” affective expression and poor eye contact. Due to her apathy and listlessness, the rapid decline in her clinical picture, and the cognitive profile evidenced, I diagnosed her with FTD.

One of the most significant recommendations I made in my report on this woman was that her prescription for Aricept (which is a popular medication, belonging to the class of acetylcholinesterase inhibitors, or AChEI, approved to treat Alzheimer’s disease) be discontinued in light of her probable FTD, because depending on who you talk to (for example, see the reference below of Boxer, Trojanowski & Lee et al., 2005) AChEI therapy can make the symptoms of FTD worse, and not better.

After seeing this woman and completing her testing report, weeks later I received a call from her physician, actually, if I remember correctly, 2-3 of them in one week. Initially thinking something was wrong, I called back. The physician excitedly reported to me that he had followed my recommendation to discontinue her Aricept prescription, and had switched her from a less activating antidepressant (Lexapro) to a more activating one (Prozac). Within weeks, the patient had apparently changed dramatically. She had become more interested in activities, her “flat” expression had gone away, and she had proceeded to become her “old self!” I was delighted, of course.

One of the lessons of this assessment was that diagnosis of dementia can matter, and sometimes profoundly. It should be noted that there are no cures for [edit] most forms of dementia (although, as a LinkedIn commenter rightly pointed out – there are some forms of dementia that are reversible, such as in the case of depression, as I pointed out previously here). In the case of FTD, there are also no effective treatments, but there are management techniques that can occasionally make a profound difference. So, when I first see families who approach me for assistance with their loved one suffering from dementia, one of the first things I find out is if a proper assessment has been done. If not, it’s one of the first things I do.

Boxer, A. L., Trojanowski, J. Q., Lee, V. Y. M., & Miller, M. J. (2005). Frontotemporal lobar degeneration. Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics.

Bozeat, S., Gregory, C. A., Ralph, M. A. L., & Hodges, J. R. (2000). Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer’s disease?. Journal of Neurology, Neurosurgery & Psychiatry, 69(2), 178-186.

Lane, G., Ratto, W. (2009). The importance of geriatric assessment in clinical

outcome: A case of frontotemporal dementia. Psychologists in Long Term Care Newsletter, 23 (3), 3-5.

Varma, A. R., Snowden, J. S., Lloyd, J. J., Talbot, P. R., Mann, D. M. A., & Neary, D. (1999). Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer’s disease and frontotemporal dementia. Journal of Neurology, Neurosurgery & Psychiatry, 66(2), 184-188.