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Clinical Therapy in Dementia and Related Diseases
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Clinical Therapy in Dementia and Related Diseases

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Mental Health".

Deadline for manuscript submissions: closed (20 March 2026) | Viewed by 8253

Special Issue Editor

Dr. Takao Yamasaki

E-Mail Website
Guest Editor
Minkodo Minohara Hospital, Fukuoka, Japan
Interests: neurology; dementia; neuroscience
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With the rapid aging of society, dementia has become a growing global concern, imposing substantial medical and economic burdens. Despite ongoing efforts, the absence of fundamental treatments and the critical need for advanced early diagnostic technologies remain significant challenges. At the same time, scientifically validated preventive strategies, non-pharmacological treatments, and approaches to enhance patients' quality of life (QOL) are increasingly recognized as essential.

A comprehensive, society-wide response is necessary to address this multifaceted issue. Clinical research and social support systems are pivotal areas of focus, demanding innovative solutions and interdisciplinary collaboration. This research topic seeks contributions addressing the following topics:

  1. Development of disease-modifying therapies (DMTs);
  2. Advancements in early diagnostic technologies;
  3. Lifestyle interventions for dementia prevention;
  4. Management of multimorbidity in dementia patients;
  5. Validation of non-pharmacological treatments;
  6. Genetic factors and personalized medicine;
  7. Targeted treatments for dementia subtypes;
  8. Improving care quality and nursing support;
  9. Digital health technologies in diagnosis and treatment;
  10. Other emerging dementia-related topics.

Dr. Takao Yamasaki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dementia
  • aging society
  • disease-modifying therapies (DMT)
  • early diagnosis
  • lifestyle interventions
  • multimorbidity management
  • non-pharmacological treatments
  • personalized medicine
  • quality of life (QOL)
  • digital health technologies

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Published Papers (6 papers)

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Research

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15 pages, 2836 KB  
Article
Early Changes in Resting-State Connectivity of the Anterior Insular Cortex Are Associated with Reductions in Pain and Catastrophizing After Total Hip Arthroplasty in Female Patients: A Preliminary Study
by Yuji Chuda, Tsubasa Mitsutake, Atsushi Kawaguchi, Takanori Taniguchi, Hisato Nakazono, Mitsunori Okita and Maiko Sakamoto
J. Clin. Med. 2026, 15(10), 3799; https://doi.org/10.3390/jcm15103799 - 14 May 2026
Viewed by 148
Abstract
Background/Objectives: Chronic pain in osteoarthritis alters large-scale brain networks, including the insular cortex and default mode network. While total hip arthroplasty (THA) provides substantial relief, the early postoperative reorganization of functional connectivity (FC) remains unclear. This longitudinal fMRI study exploratively investigated how [...] Read more.
Background/Objectives: Chronic pain in osteoarthritis alters large-scale brain networks, including the insular cortex and default mode network. While total hip arthroplasty (THA) provides substantial relief, the early postoperative reorganization of functional connectivity (FC) remains unclear. This longitudinal fMRI study exploratively investigated how early improvements in pain intensity and catastrophizing are associated with insular FC alterations following THA. Methods: In this exploratory, longitudinal observational study, 10 female patients with hip osteoarthritis underwent resting-state fMRI and clinical assessments—Pain Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS), and Japanese Orthopaedic Association (JOA) hip score—preoperatively and two weeks post-THA Whole-brain seed-to-voxel FC analyses were conducted using the bilateral anterior insular cortex as the seed. Changes in FC (ΔFC) were correlated with preoperative scores and postoperative clinical changes (ΔVAS, ΔPCS). Results: Following THA, VAS and PCS scores decreased significantly, while JOA scores improved. rs-fMRI analysis revealed that FC between the left anterior insula and major DMN regions as well as the right anterior cingulate cortex (ACC) increased significantly overall. Correlation analysis showed that greater reductions in pain intensity (ΔVAS) were significantly associated with increased ΔFC across these regions. Conversely, greater reductions in pain catastrophizing (ΔPCS) were associated with a suppression of these FC increases. Conclusions: Given the preliminary nature of this study, these findings suggest that the alleviation of pain catastrophizing following THA may be associated with the initial reorganization of the aIC network, rather than establishing a definitive causal relationship. Further large-scale longitudinal studies are required to confirm these potential neural signatures. Full article
(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)
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15 pages, 236 KB  
Article
Immersive, Open-World Virtual Reality for Dementia Care: NeuroVRX Pilot Study
by Martin Eckert, Thomas Ostermann, Jan Peter Ehlers and Gregor Hohenberg
J. Clin. Med. 2025, 14(23), 8465; https://doi.org/10.3390/jcm14238465 - 28 Nov 2025
Viewed by 1080
Abstract
Background: The increasing prevalence of Alzheimer’s disease and related dementia are a global problem generating social and economic burdens. Cognitive Stimulation Therapy is a non-pharmaceutical aid for people with dementia. In this context, digital and virtual reality approaches are underinvestigated, especially with [...] Read more.
Background: The increasing prevalence of Alzheimer’s disease and related dementia are a global problem generating social and economic burdens. Cognitive Stimulation Therapy is a non-pharmaceutical aid for people with dementia. In this context, digital and virtual reality approaches are underinvestigated, especially with respect to explorable open-world environments. The pilot aims to evaluate the feasibility, acceptability, and safety of an immersive, open-world virtual reality application for people with dementia. Methods: We conducted a single-arm, unrandomised study with three male participants diagnosed with dementia. The intervention consisted of a single virtual reality session in an immersive, open-world environment, where participants were able to explore freely while seated, using arm movements and head control to navigate an avatar. Results: All three participants finished the session without the occurrence of adverse events. The mean session time was 28 min, and the average walking distance was 0.9 km, with 1210 steps on average. Questionnaire results indicate acceptance and a positive attitude toward the usability of the intervention. We measured minimal changes in mood. Anecdotal reports indicate high immersion and autobiographical stimulation. We detected no adverse events or occurrences of cybersickness. Conclusions: Immersive, open-world virtual reality proved to be feasible, safe, and well accepted by the participants. The combination of state-of-the-art hardware and exploration-based software design enabled cognitive and motoric stimulation. The results indicate strong feasibility for the application of exploratory three dimensional virtual reality applications and further support the execution of controlled trials to assess therapeutic outcomes. Full article
(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)
16 pages, 1447 KB  
Article
Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia
by Tatsuo Nakahara, Yukiko Harada, Naho Nakayama, Kijiro Hashimoto, Naoya Kida, Toshiaki Onitsuka, Hiroo Noda, Kenji Murasugi, Yoshihiro Takimoto, Wataru Omori, Tsuruhei Sukegawa, Jun Shiraishi, Kouji Tanaka, Hitoshi Maesato and Takefumi Ueno
J. Clin. Med. 2025, 14(21), 7892; https://doi.org/10.3390/jcm14217892 - 6 Nov 2025
Viewed by 2408
Abstract
Background: Clozapine is the only antipsychotic medication proven effective in patients with treatment-resistant schizophrenia (TRS). However, many patients have serum concentrations outside the recommended therapeutic window, and clozapine exhibits substantial interindividual variability. This study aimed to (1) examine clozapine dosage and blood [...] Read more.
Background: Clozapine is the only antipsychotic medication proven effective in patients with treatment-resistant schizophrenia (TRS). However, many patients have serum concentrations outside the recommended therapeutic window, and clozapine exhibits substantial interindividual variability. This study aimed to (1) examine clozapine dosage and blood concentrations in patients with TRS; (2) investigate the effects of sex and age on dosage and blood concentrations; (3) assess clinical response to clozapine treatment; and (4) develop a random forest (RF) model to predict therapeutic response using clinical and therapeutic drug monitoring (TDM) data. Methods: Dried blood spots were used to measure concentrations of clozapine, norclozapine, and clozapine N-oxide. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). The RF algorithm was applied to analyze the relationships between biochemical and demographic factors and clinical response to clozapine. Results: A total of 754 blood samples from 167 patients were analyzed. Men received higher doses than women, and glucose levels were elevated in both sexes. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.986 for the training set and 0.852 for the testing set. Accuracy, precision, recall, and F1-score (training/testing) were 0.938/0.786, 0.936/0.736, 0.934/0.780, and 0.935/0.757, respectively. The SHapley Additive exPlanations (SHAP) analysis indicated that baseline BPRS score, treatment duration, age, and clozapine concentration were important variables contributing to the output of the model. Conclusions: Our model achieved satisfactory predictive performance for clinical response and provides valuable insights into personalized prediction of clozapine efficacy. Full article
(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)
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Review

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18 pages, 582 KB  
Review
Neurophysiological Characteristics Associated with Driving Abilities in Older Adults: A Scoping Review
by Mutsuhide Tanaka, Yuma Hidaka and Futoshi Mori
J. Clin. Med. 2026, 15(8), 2956; https://doi.org/10.3390/jcm15082956 - 13 Apr 2026
Viewed by 459
Abstract
With population aging, motor vehicle accidents involving older drivers have increased. Age-related cognitive decline affects driving performance; however, the underlying neural mechanisms remain unclear. This scoping review explored neurophysiological characteristics associated with driving in older adults, including those at risk of dementia. Following [...] Read more.
With population aging, motor vehicle accidents involving older drivers have increased. Age-related cognitive decline affects driving performance; however, the underlying neural mechanisms remain unclear. This scoping review explored neurophysiological characteristics associated with driving in older adults, including those at risk of dementia. Following PRISMA-ScR guidelines, we searched PubMed, Scopus, and CINAHL for studies examining driving-related neurophysiological measures in older adults aged ≥60 years. Twelve studies were included. Findings converge on load-dependent neural compensation failure: older adults maintain driving performance under low-to-moderate demands, but compensatory mechanisms break down under high cognitive load. Electroencephalography (EEG) studies revealed blunted midfrontal theta upregulation during high-load conditions, associated with reduced steering precision and delayed responses. Event-related potential studies demonstrated that reduced P3b amplitude was associated with missed braking responses and that abnormal visual evoked potentials in Alzheimer’s disease predicted unfit-to-drive classifications. fNIRS studies during driving-related tasks and an fMRI study using a laboratory-based visual task consistently showed prefrontal hyperactivation in older adults. Although some older adults maintained comparable performance to younger adults, the brain–behavior associations observed in younger adults were absent, suggesting that this hyperactivation does not necessarily serve a functional compensatory role. Combined with EEG evidence of impaired oscillatory modulation, these findings suggest that prefrontal hyperactivation does not necessarily compensate for diminished neural synchronization under high-load conditions. Neurophysiological markers hold promise for fitness-to-drive assessments. Future research should employ high-load scenarios and multimodal neuroimaging to verify prefrontal compensatory mechanisms. Full article
(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)
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17 pages, 315 KB  
Review
Alzheimer’s Disease: From Pathogenesis to Emerging Therapeutic Targets
by Tetsuya Takahashi and Kazuki Muguruma
J. Clin. Med. 2026, 15(6), 2357; https://doi.org/10.3390/jcm15062357 - 19 Mar 2026
Cited by 1 | Viewed by 1197
Abstract
Alzheimer’s disease (AD) is the most prevalent cause of dementia and can be conceptualized as a tauopathy initiated by the accumulation of amyloid-β (Aβ) in the brain. The clinical introduction of anti-Aβ antibody therapies has marked the beginning of a new era in [...] Read more.
Alzheimer’s disease (AD) is the most prevalent cause of dementia and can be conceptualized as a tauopathy initiated by the accumulation of amyloid-β (Aβ) in the brain. The clinical introduction of anti-Aβ antibody therapies has marked the beginning of a new era in disease-modifying treatment for dementia. While the deleterious effects of Aβ on postsynaptic spines and axonal microtubules have been increasingly clarified, recent studies have shifted attention beyond extracellular Aβ deposition as senile plaques to the pathogenic significance of intracellular Aβ. In particular, accumulating evidence highlights lysosomes as critical sites of intracellular Aβ toxicity. Interactions between Aβ and gangliosides, v-ATPase-dependent lysosomal acidification, and lysosomal membrane integrity are the key determinants of disease progression. In parallel, additional molecular players, including components of the complement cascade and asparaginyl endopeptidase, have been implicated in linking Aβ pathology to tau dysregulation and neurodegeneration. As therapeutic strategies targeting Aβ enter clinical practice, these emerging pathways represent promising targets for the next generation of AD treatment. Here, we summarize current insights and ongoing therapeutic developments centered on these mechanisms. Full article
(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)
17 pages, 595 KB  
Review
Bridging Dementia Care in Japan: The Emerging Role of General Medicine Physicians
by Takao Yamasaki
J. Clin. Med. 2025, 14(21), 7889; https://doi.org/10.3390/jcm14217889 - 6 Nov 2025
Viewed by 2232
Abstract
As global populations age, dementia has become a major public health challenge that warrants sustainable, person-centered, and community-integrated models of care. In Japan, the recent introduction of board-certified general medicine (GM) physicians, trained across both family medicine and hospital general medicine, has created [...] Read more.
As global populations age, dementia has become a major public health challenge that warrants sustainable, person-centered, and community-integrated models of care. In Japan, the recent introduction of board-certified general medicine (GM) physicians, trained across both family medicine and hospital general medicine, has created an opportunity to strengthen dementia care through improved continuity and coordination. This narrative review conceptually examines the emerging role of GM physicians within Japan’s Community-Based Integrated Care System and compares this evolving model with dementia care structures in the United States, the United Kingdom, and Canada. By synthesizing policy documents and published literature, this review outlines how GM physicians can serve as integrative actors bridging outpatient and inpatient care, collaborating with dementia specialists, Initial-phase Intensive Support Teams, and Community-based Comprehensive Support Centers to enhance person-centered support throughout the disease trajectory. While empirical outcome data remain limited, this conceptual framework highlights potential contributions of GM physicians to early detection, care transitions, and interdisciplinary collaboration in dementia care. However, challenges persist, including training variability, workforce shortages, and systemic fragmentation. By situating Japan’s experience within an international context, this review provides a conceptual basis for future empirical studies and policy development aimed at strengthening generalist-led dementia care in aging societies. Full article
(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)
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