Manabu Ikeda

Behavioral disinhibition is a core feature of behavioral variant frontotemporal dementia (bvFTD) and occurs across related FTD-spectrum presentations. Serotonergic dysfunction may contribute to behavioral dysregulation; therefore, we primarily examined dorsal raphe (DR)-centered midbrain ¹²³I-FP-CIT uptake as an indirect extrastriatal signal that may partly reflect serotonin transporter-related binding. Because striatal dopaminergic circuits support reward learning, behavioral inhibition, and context-dependent behavioral updating, striatal uptake was examined exploratorily. This retrospective exploratory study included 21 patients within the FTD spectrum who underwent Neuropsychiatric Inventory (NPI) assessment, magnetic resonance imaging, and ¹²³I-FP-CIT single-photon emission computed tomography within a 3-month window. The primary outcome was the NPI disinhibition score. DR-centered midbrain and striatal specific uptake ratios (SURs) were calculated using the cerebellum as the reference region. Age- and sex-adjusted quasi-Poisson models with a log link were fitted. DR-centered midbrain SUR was not significantly associated with disinhibition in the primary model (β = −1.027, p = 0.353). In the exploratory model, higher striatal SUR was nominally associated with lower disinhibition scores (β = −0.438, p = 0.022). The negative direction of the striatal association was generally preserved across sensitivity analyses, although nominal significance was not retained in all models. DR-centered midbrain SUR was not significantly associated with behavioral disinhibition in this small FTD-spectrum cohort. Lower striatal SUR showed a directionally consistent but sensitivity-dependent nominal association with greater disinhibition. This hypothesis-generating finding may reflect broader frontostriatal disease burden, striatal neurodegeneration, parkinsonian-spectrum overlap, or partial-volume effects and does not establish a disinhibition-specific dopaminergic mechanism.

Katakami S, et al. J Clin Neurol. 2026 Jan;22:e18. https://doi.org/10.3988/jcn.2025.0408

Background/Objectives: Dysregulated gamma oscillations are associated with cognitive dysfunction. Auditory stimulation at 40 Hz enhances neural activity in brain regions associated with learning, attention, and memory. This study assessed the safety and acceptability of 40 Hz amplitude-modulated auditory stimulation in healthy older people. Auditory stimuli were created using popular songs, where vocals and background music were separated and independently amplitude-modulated at 40 Hz with different modulation depths to generate periodic 40 Hz gamma waveforms. Methods: In this open-label, single-arm study, healthy participants aged ≥65 years received 40 Hz amplitude-modulated auditory stimulation daily via a smartphone for 28 days through earphones/headphones. Safety was assessed through adverse event (AE) monitoring and changes in clinical scores for depression, cognitive function, and hearing thresholds. Acceptability was evaluated by adherence rates, listening time, dropout reasons, volume levels, intent for future use, and subjective impressions of the sound source on a 7-point Likert scale. Results: Among 28 participants (mean age 69.1 years, 53.6% female), six reported 12 AEs, with six considered device-related (e.g., ear discomfort, jaw pain, musculoskeletal stiffness). The AEs observed were mild or moderate. Scores for cognitive function, depression, and hearing thresholds did not worsen during the study period. Adherence was observed in 96.4%, with 85.7% expressing interest in continuing. Most participants rated the sounds’ unnaturalness between 2 and 3 and discomfort between 1 and 3 on the 7-point Likert scale. Conclusions: The intervention was well tolerated and acceptable in study participants, with no major safety concerns identified. Auditory stimulation did not cause severe discomfort or reduce acceptability. Further studies should explore the long-term effects and broader clinical applications.

This study evaluated the performance of ChatGPT with GPT-4 Omni (GPT-4o) on the 118th Japanese Medical Licensing Examination. The study focused on both text-only and image-based questions. The model demonstrated a high level of accuracy overall, with no significant difference in performance between text-only and image-based questions. Common errors included clinical judgment mistakes and prioritization issues, underscoring the need for further improvement in the integration of artificial intelligence into medical education and practice.

The burden of caregivers of people with dementia with Lewy bodies (DLB) is high; however, factors related to their caregiving burden are not fully clarified. We herein investigated factors associated with increasing caregiver burden for caregivers of people with DLB. To explore factors associated with caregiver burden, a linear regression analysis was conducted using the J-ZBI_8 total score as the dependent variable and a total of 36 factors as independent variables. This analysis included 252 pairs of people with DLB and their caregivers. Caregivers’ mean J-ZBI_8 was 8.4, indicating that caregiver burden was generally high. First, we identified 20 factors associated with caregiver burden in univariable analysis. Finally, multivariable analysis found three significant factors: irritability (β = 0.208, p < 0.001), use of “short stay” or “small-scale, multifunctional home care” (β = 0.208, p < 0.001), and nighttime behavior (β = 0.138, p = 0.020) were significantly associated with J-ZBI_8 total scores. Irritability and nighttime behavior were found to be contributing factors to caregiver burden. High caregiver burden among caregivers of people with DLB may result in the use of social services providing overnight stays, but to what extent such services reduce caregiver burden is unknown.

Background: Delayed neuropsychiatric sequelae (DNS) is a syndrome that appears days to weeks after acute carbon monoxide (CO) poisoning. DNS shows various neuropsychiatric symptoms, such as mental deterioration and parkinsonism.Case Presentation: Our case was a 37‐year‐old male with schizophrenia. He attempted suicide by CO poisoning and was brought to our emergency department (Day 0). He was ventilated with normobaric oxygen therapy for 3 days and moved to the psychiatric ward with clear consciousness. We restarted antipsychotics, and he gradually presented akinesia and rigidity. Additionally, around Day 32, he showed disorganized behaviors, mental deterioration, incontinence, and gait disturbance. Brain magnetic resonance imaging (MRI) showed slightly abnormal findings on Day 35. Although we suspected DNS on the clinical course and the MRI findings, catatonia and side‐effects of antipsychotics were also considered. Finally, electroencephalography (EEG) on Day 38 with apparent abnormalities, including diffuse slow waves, resulted in our diagnosis of DNS, and he underwent hyperbaric oxygen therapy. His condition was dramatically improved, and his diffuse slow waves on EEG disappeared on Day 83. We also followed his clinical presentations and brain MRI until 33 months. Throughout the whole follow‐up, his cognition, movement, and psychiatric symptoms remained stable. However, his brain MRI showed progressive atrophy in bilateral frontal lobes and increasing white matter lesions throughout the whole course.Conclusion: EEG, as well as brain MRI, may be crucial in the differential diagnosis of DNS in patients with complex conditions involving medications and severe mental illnesses.

We investigated whether the treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers, along with their attending physicians’ perception of those treatment needs, differ according to the clinical department visited by the patients. This was a subanalysis of a multicenter, cross-sectional, observational survey study. Data from the main study were classified according to the clinical department visited by the patient: psychiatric group (P-group), geriatric internal medicine group (G-group), and neurology group (N-group). The treatment needs of patients and caregivers were defined as “the symptom that causes them the most distress”, and the frequency of each answer was tabulated. This subanalysis included 134, 65, and 49 patient–caregiver pairs in the P-, G-, and N-groups, respectively. Statistically significant differences in patient background characteristics such as patient age; initial symptom domains; use of cholinesterase inhibitors, levodopa, antipsychotics, and Yokukansan; and total scores of the Mini-Mental State Examination, Neuropsychiatric Inventory-12, and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Parts II and III were shown among the three subgroups. While there were no differences in patients’ treatment needs among the subgroups, residual analysis showed that in the N-group, parkinsonism was more of a problem than other symptom domains (p = 0.001). There were significant differences in caregivers’ treatment needs among the three subgroups (p < 0.001). The patient–physician concordance rates for the symptom domains that caused patients the most distress were: P-group, 42.9% (kappa coefficient [κ] = 0.264); G-group, 33.3% (κ = 0.135), and N-group, 67.6% (κ = 0.484). The caregiver–physician concordance rates for the symptom domains that caused the caregivers the most distress were: P-group, 54.8% (κ = 0.351), G-group, 50.0% (κ = 0.244), and N-group, 47.4% (κ = 0.170). This subanalysis revealed differences in the treatment needs of patients with DLB and their caregivers according to the clinical department they attended. There might be a lack of awareness of those treatment needs by the attending physicians, regardless of their specialty. UMIN Clinical Trials Registry UMIN000041844.