Dementia of the personality

Therapeutic development should not forget the symptoms

According to the 1983 edition of the Oxford textbook of psychiatry, “There are no specific clinical features to separate [frontotemporal dementia] from Alzheimer’s, and the distinction is generally made at autopsy not in life”.1 That was a popular view at the time — dementias are clinically all the same but sometimes pathologically different. Since then, the growth in understanding of non-Alzheimer degenerative dementias has been enormous. Careful clinical characterisation has, in turn, paved the way for numerous fundamental discoveries in pathology and genetics.

In hindsight, it seems hard to understand how, among the non-Alzheimer dementias, behavioural variant frontotemporal dementia (bvFTD) could have ever been confused with Alzheimer disease (AD). Whereas AD begins with cognitive symptoms — notably memory impairment — bvFTD begins with behavioural changes. In this issue of the MJA, Piguet and colleagues2 provide an excellent and up-to-date review of the characteristic changes.

Although bvFTD can now be clinically diagnosed with a high degree of accuracy, mistakes still occur in non-expert centres. Two common errors are the belief that bvFTD is diagnosed by neuropsychological tests, and failing to appreciate the temporal evolution of symptoms. The first of these has its origin in the assumption that bvFTD impairs executive functions — neuropsychological abilities relating, among others, to the processing of information, problem solving and multitasking.2 The problem is that executive functions are vulnerable to many factors, including cerebral pathology, psychoactive medication, pain, mood disturbance and fatigue.3,4 In contrast, some bvFTD patients do well on executive function tests while those who show executive impairments frequently do so in other cognitive domains as well; that is, the executive function deficit is not focal.5 As an example, I recall a recent patient who had been assessed for temporal lobe epilepsy surgery. A neuropsychological assessment identified focal executive dysfunction and suggested bvFTD. In fact, the patient had no clinical features of bvFTD, and the combination of chronic epilepsy and a large dose of carbamazepine was more than enough to explain the impairment shown in the tests.

Failure to appreciate the temporal evolution of symptoms means failing to recognise that the behavioural changes suggestive of bvFTD were not present at the outset of the condition. This usually occurs when a patient with AD presents late with behavioural disturbances such as restlessness and agitation. By focusing only on the presenting problem, the patient’s history of progressive cognitive impairment for (typically) years is missed. It is also worth noting that certain behaviours are more specific to bvFTD than others, particularly stereotypical behaviours and changes of food preferences.6

There are presently no treatments available to change the course of bvFTD. Given this also remains true for AD, why should it be important to make an accurate diagnosis? The standard answer in the literature is that disease-modifying therapies will likely work on specific molecular pathways, and that a specific pathological diagnosis should therefore be made at presentation. Without such treatments, however, this argument remains hypothetical. In the meantime, I would argue that an accurate diagnosis is required for the peace of mind of the family. Caregiver distress is immense in bvFTD.7 This cannot be ameliorated if caregivers are accessing information and support designed for a different disease — it can drive them, instead, to despair and insecurity if what they hear from elsewhere does not resonate with their own experience.

The profound behaviour and personality change in bvFTD is also relevant to therapeutic development. The focus in degenerative dementia for over a decade now has been on disease-modifying therapies, while novel symptomatic treatments have been largely ignored. Patients with dominantly inherited bvFTD can be identified pre-symptomatically, so therapy that delays or prevents onset is highly desirable. For the majority with sporadic disease, however, therapies that slow progression may be problematic. When I discussed the hypothetical scenario of a therapy that slowed disease progression with an FTD caregiver support group, none of the 40 or so people present said they would want such a treatment. The reason was that a disease that attacks the personality and gives rise to upsetting behaviours from the outset is not one that families may wish to prolong. To this end, more effort to develop novel therapies for the symptoms of bvFTD is needed. Given this would involve turning off unwanted behaviours, it might even be an easier nut to crack than that of attempting to switch cognition back on, as has been the aim of many symptomatic agents in AD. It is surely worth a try.