小林 良太

The introduction of anti-amyloid-β antibody therapies has fundamentally changed the clinical landscape of dementia, shifting the role of neuroimaging from diagnosis toward therapeutic decision-making. Amyloid positron emission tomography (PET) has become essential for confirming amyloid pathology and determining treatment eligibility. However, amyloid deposition is frequently observed in cognitively normal elderly individuals and in non-Alzheimer neurodegenerative disorders, indicating that amyloid status alone is insufficient to explain clinical symptoms. In this context, imaging modalities reflecting neurodegeneration, including structural magnetic resonance imaging (MRI) and functional imaging such as 18F-FDG-PET and brain perfusion single-photon emission computed tomography (SPECT), remain important for assessing disease severity and functional impairment. Furthermore, discrepancies between imaging biomarkers-such as the presence of neurodegeneration without amyloid pathology in cases clinically suspected of Alzheimer's disease, and atypical imaging patterns-are commonly encountered in clinical practice and may reflect underlying pathological heterogeneity. A multimodal imaging approach that integrates multiple biomarkers provides complementary information and may improve diagnostic accuracy and clinical interpretation. In addition, other imaging modalities, including dopamine transporter (DAT) imaging and cardiac sympathetic imaging, can contribute to the evaluation of non-Alzheimer pathologies. This review summarizes the current roles of clinically available multimodal imaging in dementia, with a focus on nuclear medicine and MRI, highlighting their complementary value and clinical implications in the era of disease-modifying therapies.

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 .