Suicide Attempt as the Presenting Symptom of C9orf72 Dementia
To the Editor: Dementia is generally considered to have a low risk of suicide, but several reports have highlighted suicide in dementia, and the exact predictors are still poorly known (1). Here we show that a suicide attempt can be the first manifestation of early dementia due to the recently identified C9orf72 expansion (2, 3). This novel type of dementia can be easily missed in elderly patients with dementia or misdiagnosed as Alzheimer’s disease (4).
A 72-year-old German man without significant previous medical or psychiatric illnesses was admitted after trying to hang himself. An adjustment disorder was assumed at first, but psychiatric examination revealed a striking lack of concern about the suicide attempt, frequent irrelevant answers, and inappropriate jocularity without any signs of depression. His wife reported a 2-year history of subtle behavioral disinhibition (short episodes of socially inappropriate behavior and impulsive reactions) and deficits in short-term memory and face recognition in her husband, but history and observation did not reveal additional symptoms necessary for a diagnosis of possible behavioral frontotemporal dementia (5). (For details of the diagnostic workup, see the data supplement that accompanies the online edition of this letter.) Neuropsychological testing results revealed mild deficits in the domains of verbal episodic memory and visuospatial abilities but not in executive functions such as strategic thinking and executive flexibility (see the online data supplement). MRI and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) revealed several abnormalities, including temporal atrophy with hippocampal degeneration and biparietal and temporomesial hypometabolism, but no frontal atrophy or hypometabolism (Figure 1). Although behavioral frontotemporal dementia can present with anterior temporal atrophy without frontal atrophy or hypometabolism (5), this imaging pattern was considered to be atypical for behavioral frontotemporal dementia or, at least, to be unspecific. The patient’s sister died by suicide at age 50, and his mother began to show late-onset progressive nonfluent aphasia at age 85. Based on this family history, C9orf72 genotyping was initiated, revealing a pathogenic expansion of more than 50 repeats (2, 3). A written informed consent was obtained from the patient after the procedures and the publication had been fully explained to him and his family.
a The coronal T2-weighted MRI scan in panel A shows substantial bilateral temporal atrophy with temporomesial predominance, including hippocampal atrophy (arrows) and concomitant (panel B) mild cerebellar atrophy (arrows). Horizontal fluid-attenuated inversion recovery-weighted MRI shows absence of frontal atrophy (panels C and D). The FDG-PET images in panel E show hypometabolism in the biparietal cortex, including adjacent parts of the cuneate and in the temporomesial cortex. No frontal hypometabolism was observed. FDG-PET images were stereotactically normalized and, after Gaussian smoothing, compared with age-matched comparison subjects to obtain z scores (blue clusters).
This case of a suicide attempt as the presenting symptom of early dementia due to a C9orf72 expansion suggests that C9orf72 dementia and associated behavioral disturbances (e.g., disturbed impulse inhibition) may present a risk factor for suicide in the elderly. As shown here, suicidal ideation and attempts might become apparent even before the criteria for behavioral frontotemporal dementia are fulfilled. Death by suicide may be unappreciated or unreported in the family history (especially if not accompanied by clear-cut dementia), and this might explain—at least in part—the high rate of apparently “sporadic” patients with C9orf72 dementia (6).
Our case demonstrates that identifying the underlying C9orf72 dementia can be complicated by the fact that results of neuropsychological testing and imaging studies can be more suggestive of Alzheimer’s disease (pronounced hippocampal atrophy, biparietal and temporomesial hypometabolism, and early deficits in episodic verbal memory and visuospatial abilities) than of frontotemporal dementia. Thus, while frontal hypoperfusion or atrophy with relative sparing of the temporal lobes has been described as a predominant pattern in several patients with C9orf72 dementia (7, 8), neurodegenerative dysfunction might be much more variable in others: C9orf72 dementia might present as “mixed dementia” with features of both frontotemporal dementia and Alzheimer’s disease. This explains why C9orf72 dementia can easily be misdiagnosed as Alzheimer’s disease (4).
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