Psychosis is more common than previously thought in frontotemporal dementia

FTD is a progressive condition so multiple aspects of cognition, function and behaviour may eventually become affected, and psychiatric states like apathy, depression, anxiety, irritability, agitation and aggression are not uncommon. In contrast, the set of symptoms known as psychosis appeared to be rare until recently.

Psychosis in dementia

Psychosis consists of hallucinations and delusions in a person who is then confused about reality. In other words, a person who appreciates that a hallucination is not real would not be said to be suffering psychosis. The everyday experience of individuals with psychosis is coloured by their hallucinations and delusions, which can drive how they act or think.

Psychosis is common in the major dementias. It is typical of Dementia with Lewy bodies, very common in Alzheimer’s disease and occurs, although to a lesser degree, in vascular dementia. It is also a frequent complication of Parkinson’s disease dementia. The psychosis in most dementias is typically dominated by visual hallucinations, with delusions often consisting of the reactions or rationalizations that follow. However delusions do occur as distinct phenomena, often taking the form of misinterpretations of real or imaginary objects, delusions of infidelity or abandonment, or beliefs such as thinking that spouses or relatives are duplicates of the original person.

Psychosis in FTD

Psychosis was previously believed to be rare in FTD. Seven years ago, investigators in California found psychosis in 2.3% of people with FTD observed for 2 years, much lower than the 17.4% rate seen in those with Alzheimer’s disease. The same year, a working group of the American Neuropsychiatric Association reviewed the medical literature, noting that 1) psychosis is uncommon in FTD, and 2) many subjects with FTD who had been erroneously diagnosed with schizophrenia or a related condition had never suffered hallucinations or delusions. Subsequently, a group in Australia linked psychosis in FTD to the youngest cases (in other words those developing illness before age 40).

A renewed interest in the symptoms of psychosis came when it was noticed that carriers of the C9ORF72 mutation, a major cause of genetic FTD discovered four years ago, frequently suffer psychosis. Indeed several reports describe psychosis, mania and suicidal depression as the first manifestation of the illness.

The latest reviews estimate that 10% of FTD cases suffer psychosis, with higher rates in carriers of the C9ORF72 and progranulin mutations. A group working in Sweden has found an even higher prevalence, 32%, in their cohort of patients that have come to autopsy, with an average age at onset of 58 years and high prevalence of dementia and psychiatric disorders in relatives. Psychosis was equally common in those with tau and TDP-43 pathology, and very frequent in those with FUS pathology, who were also the youngest cases. In contrast to the California study, the observation period was the entire duration of the illness, which may explain the higher prevalence here. Psychosis was common in those in whom neurodegeneration mainly affected the right hemisphere of the brain. In most of the people, the FTD diagnosis was missed during life, and misdiagnosis with a psychiatric disorder was common.

Summary

Psychosis in FTD is more common than we had appreciated, and it was the recognition of psychosis in carriers of the C9ORF72 mutation that highlighted this issue. The prevalence is uncertain but appears highest in hereditary cases and in those with very young onset. This is undoubtedly relevant to patient care, but the risk of missing a diagnosis of FTD, especially in younger patients, also raises diagnostic questions. More research is needed to clarify the prevalence of hallucinations and delusions, their relation to FTD onset and diagnosis, and to learn why and how they develop.

References

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Mendez MF, Lauterbach EC, Sampson SM, ANPA Committee on Research. An evidence-based review of the psychopathology of frontotemporal dementia: a report of the ANPA Committee on Research. J Neuropsychiatry Clin Neurosci. 2008;20(2):130–149.

Mendez M, Shapira J, Woods R, Licht E, Saul R. Psychotic Symptoms in Frontotemporal Dementia: Prevalence and Review. Dement Geriatr Cogn Disord. 2008 Jan 17;25(3):206–211.

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Sha SJ, Takada LT, Rankin KP, Yokoyama JS, Rutherford NJ, Fong JC, Khan B, Karydas A, Baker MC, DeJesus-Hernandez M, Pribadi M, Coppola G, Geschwind DH, Rademakers R, Lee SE, Seeley W, Miller BL, Boxer AL. Frontotemporal dementia due to C9ORF72 mutations: Clinical and imaging features. Neurology. 2012 Sep 4;79(10):1002–1011.

Shinagawa S, Nakajima S, Plitman E, Graff-Guerrero A, Mimura M, Nakayama K, Miller BL. Psychosis in frontotemporal dementia. J Alzheimers Dis. IOS Press; 2014;42(2):485–499.

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