Case report

Delirium is a clinical condition of acute brain dysfunction with multifactorial aetiology. Increasing evidence that delirium leads to an increased risk of dementia has been accumulated (Davis et al., Reference Davis2012). Delirium is also much more common in patients with dementia or chronic cognitive dysfunction. Thus, underlying neurodegeneration has been implicated as one of the factors involved in the development of delirium. Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementing disorder after Alzheimer's disease (AD). DLB is clinically characterized by progressive dementia that is frequently accompanied by cognitive fluctuation and visual hallucinations (McKeith et al., Reference McKeith2005). Although delirium shares common clinical characteristics with DLB, there is limited information regarding the relationship between delirium and Lewy body pathology (Gore et al., Reference Gore, Vardy and O'Brien2015). Here, we report a patient with an episode of delirium who was pathologically confirmed to have limbic-type Lewy body disease (LBD). She exhibited transient visual hallucinations during the delirium, but developed no core clinical features of DLB and died of pneumonia one year later. This autopsied case suggests that delirium prior to the onset of dementia may be one of the clinical phenotypes of LBD.

This 89-year-old Japanese woman had no past medical history. She lived alone at home independently. Her admission to the internal medicine ward was due to heart failure with artrial fibrillation. She developed nocturnal delirium with severe psychomotor excitement and was discharged on her second day of admission because of the difficulty in continuing intravenous therapy. After discharge, she continued to have nocturnal delirium with psychomotor excitement and her family reported that she experienced visual hallucinations of small animals at home for two days. The next day, she was admitted at the psychogeriatric hospital; at this point she scored 12 points on the Mini-Mental State Examination (MMSE). In addition to the pharmacologic management of heart failure, treatment with bromperidol (1 mg/day) was effective for the psychomotor delirium without adverse reaction. Her MMSE score improved to 25 points. Brain computed tomography (CT) showed slightly diffuse brain atrophy. The neurological examination revealed no overt abnormality. After discharge, she lived alone at home independently with home-visit care for approximately ten months. She developed delirium once more and was admitted to a psychogeriatric hospital. Clinical examinations revealed that she had elevated liver enzyme with hyperammonemia. She was given a clinical diagnosis of liver cancer and hepatic encephalopathy. Although intravenous therapy was performed, her clinical condition got worse. Three months after admission, she died of comorbid pneumonia at the age of 90 years. Duration of disease from the occurrence of the first delirium episode to her death was approximately one year. After written informed consent was obtained from her family, neuropathological examination was performed. The fixed brain weighed 935 g. Microscopic examination revealed limbic-type LBD. Moderate senile plaques and some neurofibrillary tangles (NFTs) confined to the limbic regions were observed. The Braak NFT stage was consistent with stage of III. Argyrophilic grains were also observed in the amygdala and parahippocampus. Given the density and distribution of Lewy body pathology and the moderate degree of Alzheimer-type pathology, the likelihood that the patient had DLB clinical syndrome is intermediate based on the Third Consortium DLB (CDLB) neuropathological criteria (McKeith et al., Reference McKeith2005).

Although the specificity of a clinical diagnosis of probable DLB according to core features is uniformly high, its sensitivity is generally low (McKeith et al., Reference McKeith2005). This may be due to the fact that patients with DLB pathology may have a variety of clinical presentations. Recent clinicopathological studies revealed that there is a reasonably specific association of REM sleep behavior disorder (RBD) with DLB pathology in patients with dementia and that inclusion of RBD as a core clinical feature improves the diagnostic sensitivity of the criteria (Ferman et al., Reference Ferman2011). Moreover, RBD is an early feature of DLB, with an onset typically preceding the onset of dementia by years and often decades. However, a clinical history of RBD was not obtained because she lived alone. Although she failed to fulfill the clinical criteria of DLB, several recent studies suggest that an episode of delirium with transient visual hallucinations in this patient may enable us to suspect LBD. Clinical research by Vardy et al. (Reference Vardy, Holt, Gerhard, Richardson, Snowden and Neary2014) revealed that at least one reported episode of suspected delirium is more common in DLB (25%) than AD (7%). The median time between the most recent suspected episode of delirium and the diagnosis of dementia was less than a year in both the DLB group (range 1–66 months) and the AD group (2–60 months). Auning et al. (Reference Auning2011) compared the prevalence of early symptoms prior to the dementia stage between patients with clinical diagnoses of DLB and AD. The prevalence of delirium/fluctuations of consciousness prior to the dementia was significantly higher in patients with DLB (42.6%) than patients with AD (13.8%). Sunwoo et al. (Reference Sunwoo, Hong, Choi, Park, Kim and Lee2013) reported the association between α-synuclein pathology in the stomach and post-operative delirium in patients who underwent gastrectomy. Patients with post-operative delirium had a higher frequency of α-synuclein pathology, which is major component of Lewy bodies, compared to those without. The authors suggest that post-operative delirium may represent a preclinical stage of α-synuclein related to cognitive disorders. Jicha et al. (Reference Jicha2010) also compared clinical characteristics in the mild cognitive impairment (MCI) stage between autopsy-confirmed DLB and AD. The prevalence of hallucinations/delirium in the MCI-DLB group (44%) was significantly higher than that in the MCI-AD group (0%). These results suggest that delirium is more associated with DLB pathology than AD pathology in the predementia phase, which is consistent with the occurrence of delirium prior to dementia in the present case from clinicopathological point of view. The clinical history of delirium with transient visual hallucinations in the present case may have indicated the additional neuroimaging including cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter imaging. Considering the limited information regarding the prodromal DLB state compared with that of AD (Fujishiro et al., Reference Fujishiro, Nakamura, Sato and Iseki2015), more attention should be paid to delirium as a clinical phenotype of DLB in the predementia phase. In terms of identifying the diversity and early manifestation of DLB during its clinical course, further research is needed to elucidate the relationship between delirium and LBD.