Psychosis
Hallucinations and delusions are uncommon in FTD as compared with other causes of dementia [52]. The prevalence rate of psychosis is 10-15 % in this population [53]. It is more frequent in some familial genetic forms of the disease [54]. When present, they raise the probability of a misdiagnosis of psychiatric disorder. In addition, many FTD patients present with unexplained somatic complaints, including worries about bowel function [55].
Delusions may occur at an early stage of FTD and can even be the presenting symptom. Rarely persecutory, somatic, or religious delusions or delusions of jealousy are rather observed. Delusions often have a bizarre content [9, 56-58].
Paranoid thoughts and delusions of spousal infidelity, visual hallucinations, and misidentification are described in patients with GRN mutation [59]. For instance, zooptic hallucinations were a salient feature of a late-onset phenotype resembling dementia with Lewy bodies (DLB), with visuospatial impairment, fluctuations, parkinsonism, and complex misidentification syndrome [60]: a patient with a family history of dementia presented with Fregoli’s delusion, a delusional belief that different persons were in fact a single person who changed appearance. There were no major cognitive or behavioral symptoms of the frontal type. The MRI scan showed diffuse cortical and subcortical atrophy, particularly in temporal and frontal regions with prevalence on the right hemisphere. The FDG-PET scan showed severe bilateral frontal hypometabolism extending to both parietal and temporal cortices, more pronounced on the right hemisphere. AD CSF biomarkers were within the normal ranges, but plasmatic progranulin level was very low. A GRN mutation was confirmed by genetic testing.
Up to 38 % of patients with C9orf72 mutations present with psychotic symptoms including mystic delusion, resulting in initial psychiatric diagnoses such as delusional psychosis, somatoform psychosis, or paranoid schizophrenia [61]. A further
28 % of patients with the same mutation exhibit paranoid, deluded, or irrational thinking, which are much rarer in patients without such a mutation. This led to the hypothesis that beyond FTD, C9orf72 mutations could also be a cause of late-onset psychosis. A case report of a 44-year-old man bearing a C9orf72 mutation is interesting in that regard [62]: this man was referred for a mystical delusion and visual and auditory hallucinations. There was no family history of dementia or psychiatric disorders. He was diagnosed with “delusional hallucinatory psychosis,” though a treatment with haloperidol brought no benefit. He did not show neurological symptoms for 7 years, and no atrophy nor hypometabolism was evident in neuroimaging. Mystical grandiose delusions with auditory hallucinations remained poorly controlled despite a switch for clozapine. Other case reports include a woman with delusion of pregnancy [63], a man complaining of having pieces of plastic emaning from his head, and a woman who had visions of the devil and developed strategies for keeping him at bay. Another patient had a mono-deluision of weakness of the gluteal muscles, prompting him to maintain his finger in his anus to prevent incontinence [61]. In the same article, the case of a patient with delusional parasitosis believing that he was infested by mites crawling under his skin and into his extremities is also reported. As the mites seemed to congregate in his earlobe, he could reduce their number by pinching his earlobe at regular 10-min intervals [61]. Lastly, a woman reported to the police that a man dressed in a gorilla outfit hid in her garden, and a man was convinced that had been contacted by letter or phone by dead friends and hatched plans to meet them.
Most of these patients had clinical or imaging FTD features [64]. However, long- lasting psychosis with no imaging abnormalities that did not meet the criteria for possible bvFTD has been described in patients with C9orf72 mutations [39, 65]. When parkinsonism is associated, and in the absence of motor neuron disease, the differential diagnosis of DLB is raised [66, 67]. Psychotic features including hallucinations and delusions are common in DLB, visual hallucinations being a core feature. However, there is no evidence for repeat expansions in the C9orf72 gene in DLB [68].
Tau gene mutations give a wide range of phenotypes including progressive psychosis [57] that may precede bvFTD features [58]. A patient bearing a mutation in MAPT obtained a bachelor’s degree in Engineering Technology at age 22. By that time, he became socially withdrawn, argumentative, and difficult. By age 25, he had lost his job as a teacher and was described as obstinate and emotionally blunted. He then developed stereotypical behavior. On neuropsychological assessment, he showed borderline intellectual functioning and a below-average memory performance. An MRI scan of the brain showed marked atrophy of the frontal lobes. Neurological examination was normal, and psychiatric evaluation revealed symptoms of psychosis that were not typical of schizophrenia. At age 27, further examination showed a reduced attention span and difficulties with simple abstract reasoning. The social conduct deteriorated significantly with disinhibition, theft, and violation of interpersonal space. He developed hyperorality and difficulties swallowing at age 33 and died of aspiration pneumonia at age 36.
As a whole, patients with C9orf72 mutations and/or the corresponding pathology (FTD-TDP43 type B) are more likely to show psychosis than those with other pathologies. Patients with FTD-FUS pathology may also show psychosis [53].
Behavioral Changes in the Language Variant of FTD
Behavioral changes are subtler and less socially disruptive in the language variant of FTD than in bvFTD. They are more obvious in semantic dementia, where the main characteristic changes are preference for routine; activity limitations to a few that may, however, involve complex sequences of procedure and require some skills and executive functions; stereotyped behavior; parsimony; loss of empathy; change in food preference; and lack of awareness of danger [69].
At follow-up, patients with semantic aphasia may develop severe agitation linked to their misunderstanding of the environment, which can mimic psychosis [70].
