Objective: This study aims to investigate the clinical relevance of occipital hypoperfusion in patients with Parkinson’s disease (PD) with respect to clinical phenotype and the risk of dementia conversion. Methods: We enrolled 349 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET). Patients with PD were classified into three groups based on posterior cortical perfusion patterns on early-phase 18F-FP-CIT PET images: PD with preserved posterior cortical perfusion (n=186), PD with parieto-temporal hypoperfusion (n=84), and PD with parieto-temporo-occipital hypoperfusion (n=79). Baseline clinical features and dementia conversion risk were compared across PD groups. Results: Patients with preserved posterior cortical perfusion were younger than those in the other PD groups. Compared with the other groups, the parieto-temporo-occipital hypoperfusion group tended to have lower Cross-Cultural Smell Identification Test scores, a higher prevalence of rapid eye movement sleep behavior disorder, higher Unified PD Rating Scale motor scores, and more severe reductions in striatal dopamine transporter availability. The risk of dementia conversion was lower in patients with preserved posterior cortical perfusion than in those with posterior cortical hypoperfusion. However, the risk of dementia conversion did not differ between the parieto-temporal and parieto-temporo-occipital hypoperfusion groups. Conclusion Additional occipital hypoperfusion was not associated with an imminent risk of dementia conversion in patients with PD with posterior cortical hypoperfusion. Nonetheless, occipital involvement may serve as an indicator of the diffuse malignant subtype of PD.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Background: and PurposeWe aimed to determine the effect of demographic factors on cortical thickness and brain glucose metabolism in healthy aging subjects. Methods: The following tests were performed on 71 subjects with normal cognition: neurological examination, 3-tesla magnetic resonance imaging, 18F-fluorodeoxyglucose positron-emission tomography, and neuropsychological tests. Cortical thickness and brain metabolism were measured using vertex- and voxelwise analyses, respectively. General linear models (GLMs) were used to determine the effects of age, sex, and education on cortical thickness and brain glucose metabolism. The effects of mean lobar cortical thickness and mean lobar metabolism on neuropsychological test scores were evaluated using GLMs after controlling for age, sex, and education. The intracranial volume (ICV) was further included as a predictor or covariate for the cortical thickness analyses. Results: Age was negatively correlated with the mean cortical thickness in all lobes (frontal and parietal lobes, p=0.001; temporal and occipital lobes, p<0.001) and with the mean temporal metabolism (p=0.005). Education was not associated with cortical thickness or brain metabolism in any lobe. Male subjects had a lower mean parietal metabolism than did female subjects (p<0.001), while their mean cortical thicknesses were comparable. ICV was positively correlated with mean cortical thickness in the frontal (p=0.016), temporal (p=0.009), and occipital (p=0.007) lobes. The mean lobar cortical thickness was not associated with cognition scores, while the mean temporal metabolism was positively correlated with verbal memory test scores. Conclusions Age and sex affect cortical thickness and brain glucose metabolism in different ways. Demographic factors must therefore be considered in analyses of cortical thickness and brain metabolism.

Objective: The purpose of this study was to examine the effects of the Soma experiencing motion (Soma e-motion) program on interoceptive awareness and self-compassion among novices. Methods: A total of 19 adults (clinical group=9, non-clinical group=10) participated in the intervention. Psychological and physical changes after program were qualitatively analyzed using in-depth interviews. The Korean Multidimensional Assessment of Interoceptive Awareness (K-MAIA) and the Korean version of the Self-Compassion Scale (K-SCS) were used as quantitative measures. Results: The non-clinical group showed statistically significant differences in the K-MAIA scores (z=-2.805, p<0.01) and K-SCS scores (z=-2.191, p<0.05); however, the clinical group showed no significant differences (K-MAIA: z=-0.652, p>0.05; K-SCS: z=-0.178, p>0.05). According to the in-depth interviews, the results of the qualitative analysis were categorized into five dimensions (psychological and emotional, physical, cognitive, behavioral, and aspects participants found challenging and needs improvement). Conclusion The Soma e-motion program was feasible for improving interoceptive awareness and self-compassion in the non-clinical group. However, further research is needed to investigate the clinical efficacy of the Soma e-motion program for clinical group.

Objective: This study explored the efficacy of group reminiscence therapy, incorporating traditional plays, for individuals with mild cognitive impairment (MCI) and dementia patients. Methods: We provided 10 sessions of group reminiscence therapy to 25 MCI and dementia patients. We conducted assess-ments, both before and after the program, encompassing a range of tests, namely the Mini-Mental Status Examination (MMSE), Dysexecutive Questionnaire, Zarit Burden Interview (ZBI-K), Dementia Care Assessment Packet-Instrumental Activities of Daily Living, Geriatric Depression Scale (GDS-K), and Neuropsychiatric Inventory (NPI-K). Results: Following the program, there was a significant improvement in MMSE scores for MCI patients (19.17 to 22.33, p=0.027). There was a significant improvement in NPI-K scores for dementia patients (8.05 to 3.74, p=0.006). There was a sig-nificant improvement in GDS-K scores for MCI patients (17.00 to 14.00, p=0.043). There was a significant improvement in ZBIK scores for dementia (28.53 to 17.68, p=0.001) and MCI patients (29.17 to 16.33, p=0.046). Conclusion Our study suggested that group reminiscence therapy based on traditional play might be effective in global cog-nition of MCI patients, neuropsychological symptoms of dementia patients, depression of MCI patients, and caregiver burden of all subjects.

Objectives: ：Depressive disorder and anxiety disorder frequently co-occur, even at sub-threshold level. This study aims to identify network structure of co-morbid depression and anxiety at symptom level in nonclinical population and to reveal the central symptoms and bridge symptoms of the co-morbidity. Methods: ：This study was based on 2022 Asan Youth Mental Health Screening. Patient health questionnaire (PHQ-9) and Generalized anxiety disorder scale (GAD-7) were used to assess depressive and anxiety symptoms of 810 young adult participants from community sample. Network structure of co-morbid depressive and anxiety symptoms was estimated by Isingfit model. Results: ：Depressed mood, Restlessness and Nervousness were the most central symptoms in the network. Bridge symptoms between anxiety and depression were Restlessness and Irritability. Conclusions ：This study revealed key central symptoms and bridge symptoms of co-morbid depression and anxiety in nonclinical population and provided potential insight for treatment targets to reduce co-morbidity.

Objective: To investigate whether there is a link between cognitive function and motor reserve (i.e., individual capacity to cope with nigrostriatal dopamine depletion) in patients with newly diagnosed Parkinson’s disease (PD). Methods: A total of 163 patients with drug-naïve PD who underwent 18F-FP-CIT PET, brain MRI, and a detailed neuropsychological test were enrolled. We estimated individual motor reserve based on initial motor deficits and striatal dopamine depletion using a residual model. We performed correlation analyses between motor reserve estimates and cognitive composite scores. Diffusion connectometry analysis was performed to map the white matter fiber tracts, of which fractional anisotropy (FA) values were well correlated with motor reserve estimates. Additionally, Cox regression analysis was used to assess the effect of initial motor reserve on the risk of dementia conversion. Results: The motor reserve estimate was positively correlated with the composite score of the verbal memory function domain (γ = 0.246) and with the years of education (γ = 0.251). Connectometry analysis showed that FA values in the left fornix were positively correlated with the motor reserve estimate, while no fiber tracts were negatively correlated with the motor reserve estimate. Cox regression analysis demonstrated that higher motor reserve estimates tended to be associated with a lower risk of dementia conversion (hazard ratio, 0.781; 95% confidence interval, 0.576–1.058). Conclusion The present study demonstrated that the motor reserve estimate was well correlated with verbal memory function and with white matter integrity in the left fornix, suggesting a possible link between cognition and motor reserve in patients with PD.

Objectives: ：Although subclinical depression symptoms are associated with suicidal idea, most research have focused on clinical depression such as major depressive disorder or dysthymia. The aim of this study is to investigate network structure of depressive symptom and to reveal which symptoms are associated with suicidal ideation. Methods: ：We used part of data from the seventh Korea National Health and Nutrition Examination Survey. Participants were between 19 and 65 years of age (N=8,741). Network analysis with Isingfit model is used to reveal network structure of depressive symptoms and most central symptom and edges assessed by patient health questionnaire (PHQ-9). Results: ：The most two central symptoms were psychomotor activity and suicidal ideation. The strongest edge was psychomotor activity-suicidal ideation. Suicidal ideation also has strong association with depressive mood and worthlessness. Conclusions ：These results suggest that psychomotor activity and suicidal ideation can serve as treatment target for subclinical depression and psychomotor activity, worthlessness and depressed mood may be important factor for early intervention of suicidal ideation.