Implications for Diagnosis and Management Pharmacological Interventions

As previously mentioned, identifying behavior symptoms is relevant for diagnosis since they are more likely to occur in frequency and severity in the context of FTLD rather than AD [13, 58]. The identification of patterns of behavior change associated with specific PPA profiles might contribute to a more accurate diagnosis of the PPA syndromes and, as a consequence, help in differential diagnosis by predicting the underlying disease process. Furthermore, early detection of these behavior changes implicates a specific management, therapeutic options, and global outcome.

PPA is a devastating progressive disorder for which a specific pharmacological treatment is presently unavailable. This leaves the clinician with a few therapeutic options, the majority of which relying upon off-label use of medication for symptomatic management that lacks quality evidence from robust randomized, placebo- controlled clinical trials [59].

Compared with AD, the cholinergic neurons in brains of patients with FTLD are relatively intact [60]. Given the relative preservation of the cholinergic system, a benefit from using cholinesterase inhibitors in this condition, as in AD, is not expectable. Nonetheless, a number of small trials have been conducted in FTLD with rivastigmine, donepezil, and galantamine, but results have shown that they do not improve cognition or behavior in FTLD [61-64]; on the contrary, they may aggravate behavior disturbance [65].

Most behaviors tend to be treated with selective serotonin reuptake inhibitors (SSRIs) based on the premise that they usually respond to this class of drugs in primary psychiatric diseases. Several trials have been conducted to ascertain the impact of different SSRIs in the management of behavior changes in FTLD. These include paroxetine [66], sertraline [67], trazodone [68], fluvox- amine [69], citalopram [70], and moclobemide [71]. With the exception of paroxetine, modest positive effects on behavior, assessed with the NPI, were observed, giving some good overall clinical evidence that the serotonergic antidepressants have potential for reducing behavioral disturbances, in particular disinhibition, apathy, repetitive behaviors, sexually inappropriate behaviors, and hyperorality [72, 73].

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