小林 良太

BACKGROUND: Delirium is a common neuropsychiatric syndrome in hospitalized patients and is associated with increased mortality and poor outcomes. This study examined whether a brief bedside assessment of attention and orientation is associated with clinical outcomes in delirium. METHODS: This prospective observational study included acutely hospitalized patients with delirium who underwent psychiatric consultation at a general hospital. Attention and orientation were assessed during the initial daytime bedside consultation using a brief cognitive assessment completed within a few minutes. Patients were classified into high cognitive function (HCF) and low cognitive function (LCF) groups based on receiver operating characteristic analysis. Primary outcomes were delirium remission at 1 week and mortality at 6 months. Multivariable logistic regression and Cox proportional hazards models were used to examine associations between cognitive performance and outcomes, adjusting for major covariates. RESULTS: Ultimately, 65 patients were included. Delirium remission at 1 week occurred in 90.0% and 22.2% of patients in the HCF and LCF groups, respectively. The overall 6-month mortality rate was 30.8%, with rates of 5.0% and 42.2% in the HCF and LCF groups, respectively. In multivariable analyses, LCF was independently associated with higher 6-month mortality (hazard ratio 13.51, 95% confidence interval [CI] 1.52-120.6; odds ratio 32.7, 95% CI 2.12-503.5). The HCF group showed higher odds of delirium remission at 1 week (odds ratio 18.3, 95% CI 2.45-136.0). CONCLUSIONS: A simple cognitive assessment focused on attention and orientation may provide useful prognostic information for delirium management in general hospitals.

PURPOSE: Astrocytes colocalize with fibrillar amyloid-β (Aβ) plaques in postmortem Alzheimer's disease (AD) brain tissue; however, their spatiotemporal dynamics in vivo remain poorly understood. This multicenter study aimed to investigate the progression of astrocyte reactivity across the AD continuum, including healthy controls (HC), mild cognitive impairment (MCI), and AD, using the novel monoamine oxidase B (MAO-B)-specific PET tracer [18F]SMBT-1, while exploring its association with cognitive performance and amyloid burden. METHODS: A total of 91 participants (35 HC, 44 MCI, 12 AD) underwent [18F]SMBT-1 PET, amyloid PET, T1-weighted MRI, and standardized neuropsychological assessments. Standardized uptake value ratios (SUVRs) were calculated based on [18F]SMBT-1 PET data using four reference regions for subgroup comparisons stratified by Aβ status. RESULTS: [18F]SMBT-1 uptake was significantly elevated in amyloid-positive MCI (MCI+) and AD groups compared with amyloid-negative HC (HC-) in the frontal, temporal, and posterior cingulate regions. Notably, astrogliosis patterns distinguished MCI subtypes: MCI+ individuals exhibited a widespread AD-like pattern, whereas the MCI- group showed a distinct profile. Furthermore, the uptake in symptomatic MCI+ individuals was significantly higher than that in asymptomatic HC+ individuals. Regional SMBT-1 uptake also strongly correlated with greater Aβ burden and worse cognitive scores. CONCLUSION: This study demonstrates that [18F]SMBT-1 is a promising tool for characterizing the spatial pattern and magnitude of reactive astrogliosis across the Aβ-defined AD continuum. Our findings further suggest that astrogliosis may represent an important mechanistic link between amyloid pathology and cognitive impairment, supporting its potential relevance in therapeutic development. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs031210602, registered Feb. 07, 2022. URL FOR THE TRIAL REGISTRY: https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031210602 .

Few studies have longitudinally evaluated Hashimoto's encephalopathy with anti-NH2-terminal α-enolase (anti-NAE) antibodies using detailed imaging and neuropsychological assessments. We present the case of a man in his 50s who presented with acute hallucinations, catatonia, seizures, and cognitive decline. Initial MRI revealed diffuse white matter hyperintensities, and SPECT revealed widespread hypoperfusion. These symptoms improved with immunotherapy, but progressive frontal and temporal atrophy and residual hypoperfusion appeared over 33 months. His cognitive function improved, but he remained impaired, with persistent disinhibition and perseveration. This case suggests that Hashimoto's encephalopathy with anti-NAE antibodies can cause lasting structural and functional brain abnormalities and cognitive impairments, requiring long-term neuroimaging and neuropsychological follow-up.

Frontotemporal lobar degeneration (FTLD) encompasses frontotemporal dementia and related neurological disorders including motor neuron disease and movement disorders. During the 21th century, analyses of aggregative proteins suggested powerful hypotheses of gain-of-neurotoxicity or loss-of-function for aggregation-related proteins. However, recent translational researches in collaboration of basic studies and human pathology indicate that FTLD arises from more complex molecular mechanisms than dyshomeostasis of single molecules. Additionally, accumulation of clinicopathological evidences from various countries, genetic backgrounds or clinical specialties (e.g. neurology and psychiatry), suggests diverse phenotypes of FTLD, which are indicative of future paradigm-shift in the concept of FTLD. In this paper, we discuss FTLD pathomechanism on the basis of human pathology.