Neuropsychiatric Symptoms in FTD

Neuropsychiatric symptoms are common in dementias overall, but they are a true hallmark of bvFTD since they are inaugural and predominant throughout most of the disease, until the final loss of independence in activities of daily living. Since they usually precede the cognitive symptoms, failure to recognize the early stage of illness is the most troublesome aspect reported by carers [8]. Psychiatrists are often consulted first, and a third to a half of the patients receive a psychiatric diagnosis (e.g., depression, bipolar disorder, schizophreniform psychosis, depression with obsessive-compulsive feature, or alcohol dependence with hypomanic features), although “atypical” features are usually documented [9-11]. There is indeed a syndromic overlap between FTD and psychiatric disorders that may appear in late adulthood [12]. When dementia has become conspicuous and a neurodegenerative process is no longer in doubt, personality and behavioral changes can differentiate FTD from AD, even when described by a relative, years after the patient’s death

[13]. At the same level of functional disability, neuropsychiatric symptoms in FTD compared to AD patients cause a higher burden and distress in carers [14, 15]. The most frequent behavioral changes are the ones quoted in the International bvFTD Criteria Consortium (FTDC) [16]. Three of the six behavioral/cognitive symptoms must be present to meet diagnosis of possible or probable bvFTD (Table 13.1).

Symptoms must be persistent or recurrent rather than single or rare events. In patients with mild dementia (MMSE score > 18), the Frontotemporal Behavioral Scale helps to attribute these symptoms to FTD rather than to Alzheimer’s disease (AD) or vascular dementia [17]. The behavioral changes, assessed with a structured interview, are clustered under four headings corresponding to a common behavioral dysfunction: (i) self-monitoring dyscontrol linked with impulsiveness, related to serotonergic dysfunction; (ii) self-neglect and home neglect; (iii) self-centered behavior (apathy, perseverative stereotyped behavior, social neglect, and hypo-

Table 13.1 Behavioral/cognitive symptoms ofbvFTD [16]

chondriasis); and (iv) affective changes (elation, apparent sadness, flat affect, and emotionalism). A score of 1 is attributed to each heading if at least one symptom is present, whatever the number of items present, and the maximum score is 4. A score >3 differentiates FTD from AD and vascular dementia at mild stage [17]. Indeed, a change from the prior personality and behavior occurring early, or a fortiori preceding cognitive dysfunction, is most suggestive of FTD. None of these behavioral symptoms is specific to bvFTD; it is their combination that defines bvFTD.

Other scales can be useful to quantify these behavioral and affective changes. The Neuropsychiatric Inventory (NPI) [18], the Cambridge Behavioral Inventory [19], and the Frontal Behavioral Inventory [20] are among the most used. DAPHNE, a swift scale adapted from the FTDC criteria, was recently validated for bvFTD diagnosis and follow-up [21] . Standardized evaluation of social cognition represents one of the recent progresses of the neuropsychology of FTD. One such example is the Social Cognition and Emotional Assessment (SEA), whose five subtests assess a specific orbitofrontal-related function (identification of facial emotions, reversal/extinction task, behavioral control task, theory of mind test, and apathy scale) [22]. Some scales were specifically conceived to assess the severity and progression over time, such as the FTLD-specific Clinical Dementia Rating (FTLD- CDR) [23] and the Frontotemporal Dementia Rating Scale (FTD-FRS) [24]. The FTLD-CDR adds language and behavior to the CDR used in AD therapeutic trials. The FTD-FRS is a scale of 30 questions derived from the Cambridge Behavioral Inventory and Disability Assessment for Dementia, which captures the behavioral changes and impairment in activities of daily living in FTLD.