Search

The triad of cerebellar ataxiology is the cerebellar motor, vestibular, and cerebellar cognitive affective / Schmahmann syndrome (CCAS). The CCAS affective component comprises 5 domains: Attentional control, Emotional control, Autism spectrum, Psychosis spectrum, and Social Skill Set, each with hypermetric / overshoot and hypometric / undershoot poles reflecting the dysmetria of thought and universal cerebellar transform theories. There is no validated screening instrument to assess neuropsychiatric impairments in patients with cerebellar disorders. To examine the psychometric properties of our Cerebellar Neuropsychiatric Rating Scale (CNRS) that explores these symptoms and behaviors in patients with cerebellar disorders, 21 adults with ataxia completed the CNRS and other validation measures: the Behavior Rating Inventory of Executive Function-Adult Version Informant Report, Adult Behavior Checklist, Older Adult Behavior Checklist, Neuropsychiatric Inventory Questionnaire. We examined CNRS internal consistency using Cronbach's alpha, assessed item to subscale correlations, studied ceiling and floor effects, and convergent construct validity between CNRS and validity measure subscales. Internal consistency was α > 0.70 for each of the five domains. Subscale structure was generally confirmed: 86% of correlations between CNRS and validity subscales were significant. There were no ceiling effects. Item to subscale correlations indicated adequate reliability for total scale and subdomains. NPI-Q and CNRS scores were correlated, and 86.4% (19/22) of conceptually related subscales were significant. The CNRS is a reliable and valid measure of cerebellar neuropsychiatry. Further development can refine the instrument and shed light on the patient experience of their affective dysregulation and its clinical meaningfulness., Competing Interests: Declarations. Competing Interests: Dr. Schmahmann is the inventor of the Brief Ataxia Rating Scale, the Cerebellar Cognitive Affective / Schmahmann Syndrome Scale, the Patient Reported Outcome Measure for Ataxia, and the Cerebellar Neuropsychiatric Rating Scale, with copyrights held by the Massachusetts General Hospital Corporation. Clinical Trial Number: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The differential mechanisms between proteinopathies and neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remain unclear. To address this issue, we conducted a voxel-based morphometry and cerebrospinal fluid biomarker (α-synuclein, Aβ42, t-Tau and p-Tau 181 ) level correlation study in patients with DLB, AD and mixed cases (AD + DLB). Cerebrospinal fluid samples obtained by lumbar puncture and whole-brain T1-weighted images were collected in the AlphaLewyMA cohort. Within the cohort, 65 DLB patients, 18 AD patients, 24 AD + DLB patients and 16 neurological control subjects (NC) were clinically diagnosed. Correlation analyses were performed between cerebrospinal fluid biomarker levels and gray matter volumes using a voxel-based morphometry approach. A mediation analysis was performed to explore the role of gray matter volumes in the relationship between Aβ42 levels and clinical severity (MMSE scores). We observed a significant positive correlation between gray matter volumes and cerebrospinal fluid Aβ42 levels in the insula, the striatal regions, the right thalamus, and the claustrum in DLB patients (p FDR  < 0.05). Mediation analysis revealed that gray matter volumes significantly mediated the relationship between Aβ42 levels and MMSE scores in DLB patients. We found no significant correlation with gray matter volumes for α-synuclein, p-Tau 181 or t-Tau in DLB patients (p FDR  < 0.05). We found no significant correlations in the AD, AD + DLB and NC groups for any of the biomarkers (p FDR  < 0.05). The specific correlation between a reduced cerebrospinal fluid Aβ42 level and lower gray matter volumes in insula, striatum, thalamus, and claustrum in DLB patients suggests a prominent role for amyloidopathy in promoting brain atrophy in key regions of the disease., Competing Interests: Declarations. Ethics approval and consent to participate: This research was approved by the local ethics committee (“Comité de Protection des Personnes Strasbourg Est IV” [CPP-EST-IV]). All participants provided informed consent to participate. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Background: Dementia is associated with psychiatric symptoms but the effects of antidepressants on cognitive function in dementia are understudied. We aimed to investigate the association between antidepressants and cognitive decline in patients with dementia, and the risk of severe dementia, fractures and death, depending on antidepressant class, drug, and dose. Methods: This is a national cohort study. Patients with dementia registered in the Swedish Registry for Cognitive/Dementia Disorders-SveDem from May 1, 2007, until October 16, 2018, with at least one follow-up after dementia diagnosis, and who were new users of antidepressants, were included. Antidepressant use as a time varying exposure defined during the 6 months leading up to dementia diagnosis or each subsequent follow-up. We used linear mixed models to examine the association between antidepressant use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores. We used Cox proportional hazards models to calculate the hazard ratios for severe dementia (MMSE score < 10), fracture, and death. We compared antidepressant classes and drugs, and analyzed dose–response. Results: We included 18740 patients (10 205 women [54.5%]; mean [SD] age, 78.2[7.4] years), of which 4271 (22.8%) received at least one prescription for an antidepressant. During follow-up, a total of 11912 prescriptions for antidepressants were issued, with selective serotonin reuptake inhibitors (SSRI) being the most common (64.8%). Antidepressant use was associated with faster cognitive decline (β (95% CI) = − 0.30(− 0.39, − 0.21) points/year), in particular sertraline (− 0.25(− 0.43, − 0.06) points/year), citalopram (− 0.41(− 0.55, − 0.27) points/year), escitalopram (− 0.76(− 1.09, − 0.44) points/year), and mirtazapine (− 0.19(− 0.34, − 0.04) points/year) compared with non-use. The association was stronger in patients with severe dementia (initial MMSE scores 0–9). Escitalopram showed a greater decline rate than sertraline. Compared with non-use, dose response of SSRIs on greater cognitive decline and higher risks of severe dementia, all-cause mortality, and fracture were observed. Conclusions: In this cohort study, current antidepressant use was associated with faster cognitive decline; furthermore, higher dispensed doses of SSRIs were associated with higher risk for severe dementia, fractures, and all-cause mortality. These findings highlight the significance of careful and regular monitoring to assess the risks and benefits of different antidepressants use in patients with dementia. [ABSTRACT FROM AUTHOR]

Identifying individuals at-risk for dementia is one of the critical objectives of current research efforts, highlighting the need for simple, cost-effective, and minimally invasive biomarkers. Mild behavioral impairment (MBI), characterized by the emergence of persistent neuropsychiatric manifestations in older adults, has attracted increasing attention as a potential early indicator of cognitive decline and dementia. A growing number of studies have recently begun to explore the relationship between MBI and several blood-based biomarkers associated with Alzheimer's disease (AD) pathology, neurodegeneration, as well as systemic metabolic and inflammatory dysregulation. In this context, MBI has been associated with lower plasma Aβ42/Αβ40 ratio, higher plasma phosphorylated tau at threonine 181 (p-tau181), increased neurofilament light chain (NfL) levels, as well as disturbances in metabolic markers, including homocysteine, insulin and ferritin, suggesting a multifaceted neurobiological basis for this syndrome. These findings offer insights into the underlying pathophysiology of MBI, and connection between neuropsychiatric symptoms and progression of AD. In this narrative review, we aim to summarize and critically discuss the emerging literature evidence linking MBI to blood-based biomarkers, hoping to shed more light on MBI's pathophysiology, its connection to AD-related neurobiology, as well as its potential practical utility for predicting cognitive impairment, guiding early interventions and managing the risk for dementia. [ABSTRACT FROM AUTHOR]

Background: Pharmacological treatment of behavioral and psychological symptoms of dementia is of limited benefit. The addition of non-pharmacological interventions is often essential for optimal symptom control. Music is a viable way to help patients communicate and improve their quality of life. Objective: This study aims to find the most effective way to use music in a busy dementia ward. Methods: 17 inpatients (aged 63–93 years) with a clinical diagnosis of Alzheimer's disease and dementia took part over five weeks. Music lyrics presented via free-field speakers were individualized to personal preferences. Instruments (e.g., maracas) were used in some group sessions. We used the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Music in Dementia Assessment Scales (MiDAS) to evaluate patients' behavior before and after musical intervention. Results: There was a significant difference in mean NPI-Q scores before and after the music intervention. Specifically, Delusion, Motor Disturbances, and Agitation scores were significantly reduced after music intervention. This was accompanied by significant improvements in Interest, Response, and Enjoyment of MiDAS items during specific intervals. Conclusions: Clinical professionals can successfully deliver music-based intervention to inpatients with advanced dementia to help manage their behavioral symptoms in the short term. Music-based interventions' use for inpatient wards must be further investigated as an economical and personalized non-pharmacological therapeutic tool for patients with dementia. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine the potential added value of including neuropsychiatric symptoms (NPS) in machine learning (ML) models, along with demographic features and Alzheimer's disease (AD) biomarkers, to predict decline or non-decline in global and domain-specific cognitive scores among community-dwelling older adults. Objective: To evaluate the impact of adding NPS to AD biomarkers on ML model accuracy in predicting cognitive decline among older adults. Methods: The study was conducted in the setting of the Mayo Clinic Study of Aging, including participants aged ≥ 50 years with information on demographics (i.e., age, sex, education), NPS (i.e., Neuropsychiatric Inventory Questionnaire; Beck Depression and Anxiety Inventories), at least one AD biomarker (i.e., plasma-, neuroimaging- and/or cerebrospinal fluid [CSF]-derived), and at least 2 repeated neuropsychological assessments. We trained and tested ML models using a stepwise feature addition approach to predict decline versus non-decline in global and domain-specific (i.e., memory, language, visuospatial, and attention/executive function) cognitive scores. Results: ML models had better performance when NPS were included along with a) neuroimaging biomarkers for predicting decline in global cognition, as well as language and visuospatial skills; b) plasma-derived biomarkers for predicting decline in visuospatial skills; and c) CSF-derived biomarkers for predicting decline in attention/executive function, language, and memory. Conclusions: NPS, added to ML models including demographic and AD biomarker data, improves prediction of downward trajectories in global and domain-specific cognitive scores among community-dwelling older adults, albeit effect sizes are small. These preliminary findings need to be confirmed by future cohort studies. [ABSTRACT FROM AUTHOR]

We examine the efficacy of the Individualized Coordination and Empowerment for Care Partners of Persons with Dementia (ICECaP), an intervention that involves one-on-one individualized support from a dementia care coordinator for a dementia care partner, compared to an active control group. At least once monthly contact is made from a dementia care coordinator to the dementia care partner by telephone, video conferencing, email, or in-person support at clinical visits for the person with dementia. In this pilot randomized unblinded control trial of ICECaP, n = 61 (n = 90 randomized) care partners completed 12-months of the ICECaP intervention and n = 69 (n = 92 randomized) care partners received routine clinical support (controls) in an outpatient memory care clinic at an academic medical center, from which the participants were recruited. Early termination endpoints (death and higher level of care) and trial drop out were comparable across groups. Primary efficacy outcomes were evaluated by comparing changes in care partner mental health, burden, and quality of life from baseline to 12-months between ICECaP and controls. Linear mixed-effects model with covariate adjustment revealed no significant group differences in longitudinal changes on measures of caregiving burden, care partner depression, anxiety, quality of life, or reactions to the behavioral symptoms of the person with dementia. Hypothesized reasons for lack of initial efficacy on primary 12-month outcomes are discussed. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis is crucial to the optimal management of patients with cognitive impairment due to Alzheimer's disease (AD) or AD-related dementias. For some patients, early detection of cognitive impairment enables access to disease-modifying therapies. For all patients, it allows access to psychosocial supports. Patients typically first present their concerns about their cognition to a primary care provider, but in this setting, cognitive impairment is commonly underdiagnosed. There is also high variability in how cognitive evaluations are performed. We sought to understand barriers to and facilitators of cognitive evaluations in primary care, map barriers to implementation strategies, and gain consensus from stakeholders on possible strategies to improve dementia diagnosis in primary care. Methods: Semi-structured interviews conducted with primary care providers (PCPs). We used the Consolidated Framework for Implementation Research to inform our question guide and analysis, and incorporated chart-stimulated recall – using actual patients who had cognitive complaints who had presented to these providers – to understand clinicians' medical decision-making processes. These data were used to map identified barriers and facilitators to targeted implementation strategies. Then, this candidate list of strategies was presented to an expert stakeholder panel including clinicians and clinical operations specialists. Through a modified Delphi process, the list was narrowed to select the most promising strategies to incorporate in an intervention to improve cognitive evaluations in primary care. Results: Twenty PCPs were interviewed and mentioned barriers included lack of expertise to perform or interpret an assessment, time pressures, lack of incentives, competing priorities, lack of decision-making supports, and limited access to dementia specialists. Facilitators included the presence of an informant or caregiver and having additional staff to conduct cognitive testing. Implementation mapping resulted in a list of 15 candidate strategies. Using the modified Delphi process, these were narrowed to six. Conclusions: We used a rigorous process to identify barriers to and facilitators of cognitive assessments in primary care, identify promising implementation strategies to address these barriers, and obtain the feedback of front-line users on these strategies. This holds substantial promise for improving cognitive assessments in primary care in future implementation trials. [ABSTRACT FROM AUTHOR]

Objective: To study the use of a dementia screening tool in our clinic cohort of adults with Down syndrome. Study Design: A retrospective chart review of patients with Down syndrome was conducted to follow the use of the Adaptive Behaviour Dementia Questionnaire (ABDQ) in a dementia screening protocol. The ABDQ results for patients aged 40 years and older at a Down syndrome specialty clinic program were assessed. Based on caregiver feedback, an ABDQ with modified instructions was piloted and the impact assessed. Results: As part of our clinic's initiative to implement a new clinical protocol to screen for dementia, the ABDQ was completed by 47 caregivers of adults with Down syndrome, aged 39 years and above, from December, 2021 to April, 2023. Based on clinical impressions at the same timepoint, the ABDQ had a sensitivity of 0%, specificity of 97.4%, positive predictive value of 0%, and negative predictive value of 80.4%. Nine patients were deemed to have mild cognitive impairment and/or dementia by clinical impressions, but they did not identify as positive on the ABDQ. The Down syndrome clinic team modified the ABDQ in an effort to provide clearer language and increased sensitivity. The modified ABDQ showed a sensitivity of 0%, specificity of 93.8%, positive predictive value of 0% and negative predictive value of 75%. Conclusion: Neither the original ABDQ nor a modified version adequately identified patients with cognitive impairment and/or dementia within the Down syndrome clinical program. The inability to replicate findings from the initial ABDQ validation may be due to differences in setting and format. [ABSTRACT FROM AUTHOR]

Background: Apathy in patients with Alzheimer's disease (AD) is associated with significant morbidity and is often one of the first neuropsychiatric symptoms to present in mild cognitive impairment (MCI). Apathy is associated with accelerated cognitive decline and atrophy in fronto-striatal regions of the brain. Previous work has shown a link between apathy and the APOE gene in the context of AD, as the APOE ε 4 allele is already known to be associated with the onset of AD. However, other genetic associations with apathy are largely unexplored. Objective: To examine whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with MCI and AD. Methods: In a sample of individuals with AD (n = 266), MCI (n = 518), and cognitively normal controls (n = 378), a partial least squares correspondence analysis modeled interactions between single nucleotide polymorphisms, structural whole-brain imaging variables, and apathy. Results: An interaction was found between apathy, the possession of an APOE ε4 allele combined with minor homozygosity for the DAT1 (dopamine transporter 1) gene, and regional brain atrophy. This interaction was closely linked to the MCI and AD groups. Conclusions: The results point to an association of a dopaminergic genetic marker and apathy in the AD continuum and may inform future design of clinical trials of apathy, as well as new treatment targets. [ABSTRACT FROM AUTHOR]

Background: The lived experience of Parkinson's disease (PD) includes motor and non-motor symptoms. There is a need to capture the earliest patient experiences in a sensitive and reliable manner for the successful development of interventions that may delay clinical progression in PD., Objective: Our aim was to synthesize published literature about patient-reported symptoms in prodromal and early motor stages of PD and develop a conceptual framework of the earliest lived experiences in PD., Methods: We conducted a scoping review of the published literature in MEDLINE, EMBASE, SCOPUS, and CINAHL databases and abstracted patient-reported symptoms from included studies reporting on prodromal or early motor stages of PD populations., Results: We included 59 articles with data from 64 cohorts (prodromal PD: n = 20/64; 31%, early motor PD: n = 44/64, 69%). Overall, the 10 most frequent symptoms (of 85 standardized reported symptoms [SRSs]) were non-motor. SRSs were grouped into symptom domains (behavioral, cognition, dysautonomia, motor, sensory, sleep, and others) and functional domains (activities of daily living, communication, sexual, and social impairment). The Movement Disorder Society sponsored revision of the Unified Parkinson's Disease Rating Scale parts Ib and II (n = 13/64, 20%) and ad hoc questionnaires (n = 12/64, 19%) were the most frequently used measurement tools., Conclusion: At prodromal and early motor stages of PD, individuals report symptoms of a diverse range of motor and non-motor domains and higher-level functional domains. There is a need to capture the full spectrum of this lived experience in a new patient-reported clinical outcome measure for clinical trials in the earliest clinical stages of PD., (© 2025 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Introduction: Cognitive impairment (CI) is a common non-motor symptom of Parkinson's disease (PD). However, the diagnosis and prediction of CI progression in PD remain challenging. We aimed to explore a multi-omics framework based on machine learning integrating comprehensive radiomics, cerebrospinal fluid biomarkers, and genetics information to identify CI progression in early PD., Methods: Patients were first diagnosed with PD without CI at baseline. According to whether CI progressed within 5 years, patients were divided into two groups: PD without CI and PD with CI. Radiomics signatures were extracted from patients' T1-weighted MRI. We used machine learning methods to construct radiomics, hybrid, and multi-omics models in the training set and validated the models in the testing set., Result: In the two groups, we found 7, 23, and 25 radiomics signatures with significant differences in the parietal, temporal, and frontal lobes, respectively. The radiomics model using the 25 signatures of the frontal lobe had an accuracy of 0.833 and an AUC (area under the curve) of 0.879 to predict CI progression. In addition, the hybrid model fused with the cerebrospinal fluid Aβ level had an accuracy of 0.867 and an AUC of 0.916. In our study, the multi-omics model showed the best predictive performance. The accuracy of the multi-omics model was 0.900, and the average AUC value after five-fold cross-validation was 0.928., Conclusion: Radiomics signatures have a recognition effect in the CI progression in early PD. Multi-omics frameworks combining radiomics, cerebrospinal fluid biomarkers, and genetic information may be a potential predictor of CI progression in PD., Competing Interests: Declarations. Ethical Approval: This study was based on an open-source, public database; therefore, the requirement for written informed consent from participants was waived. Conflict of interest: Yang Luo, YaQin Xiang, JiaBin Liu, YuXuan Hu, and JiFeng Guo declare no conflicts of interest., (© 2025. The Author(s).)

Objectives: Many individuals with dementia with Lewy bodies (DLB) die of disease-related complications, but predicting the end of life can be challenging. We identified a phenotype associated with approaching end of life., Methods: We present 4 exemplar cases where individuals with DLB experienced refractory psychosis before death. We reviewed codebooks and quotes from 3 studies regarding end-of-life experiences in DLB to identify experiences that aligned with this phenotype., Results: In addition to the 4 cases, family caregivers in prior studies described prominent worsening of psychosis before death in some individuals with DLB. The worsening often occurred several months before death and was sometimes associated with rapid deterioration. Worsening psychosis was the prominent symptom and was not initially accompanied by cognitive or physical decline. In many cases, the refractory psychosis resulted in inpatient psychiatric hospitalization or residential care, but these scenarios were challenging because of the individual's behavior., Conclusion: Refractory psychosis in DLB, particularly out of proportion to other symptoms, may be a signal of approaching the end of life. More research is needed to understand this phenomenon and to develop effective and safe treatments for psychosis in DLB., Competing Interests: M.J.A. receives research support from the NIH (R01AG068128, P30AG047266, R01NS121099, R44AG062072), the Florida Department of Health (grants 20A08, 24A14), and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. She serves on the DSMBs for the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium and the Alzheimer’s Disease Cooperative Study. She has provided educational content for Medscape, PRIME Inc., and Vindico CME. J.E.G. is the creator of the QDRS and the LBCRS. He receives research support from the National Institutes of Health (R01NS101483, R01NS101483S1, R01AG071514, R01AG071514S1, R56AG074889, P01AG066584, R01AG071643, R01AG069765, R01AG057681, P30AG059295, RF1AG075901, R01AG078214. S06GM142115, R01AG056531, R01AG068128, P30AG066506) and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. He serves as a consultant for Alpha Cognition, Biogen, Eisai, Eli Lilly, GE Healthcare, Genentech, Roche. He is an investigator on clinical trials with CND Life Sciences, Cognition Therapeutics, and EIP Pharma. He serves as Chief Scientific Officer for Cognivue. He serves on the Board of Directors for the Lewy Body Dementia Association, Lewy Body Dementia Resource Center, and South Florida Chapter of the Alzheimer’s Association (all unpaid). C.M. receives research support from ACL/DHHS (90ALGG0014-01-00), NIA/NIH (2SB1AG037357-04A1, R01-AG-054435), HRSA (U1QHP287440400) and DoD (AZ190036). She is the local PI of a Lewy Body Dementia Association Research Center of Excellence. B.F.B. has served as an investigator for clinical trials sponsored by Biogen, Alector, and Transposon. He serves on the Scientific Advisory Board of the Lewy Body Dementia Association, Association for Frontotemporal Degeneration, and Tau Consortium. He is the site PI of a Lewy Body Dementia Association Research Center of Excellence program, as well as coordinating center PI of the program. He receives research support from the NIH, the American Brain Foundation, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Ted Turner and Family Functional Genomics Program. G.M.P. receives research support from the NIH U19AG033655 and R01 MH123552. He has consulted for GE Healthcare. A.S.T. is an employee of the Lewy Body Dementia Association. B.P. receives research support from NIA/NIH (1K23AG073575). J.E.F. receives research support from the NIH (R01AG079128, U19AG078105, 2U01NS100610), and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. Her institution has received research support for clinical trials sponsored by Cognition Therapeutics and EIP Pharma. She serves on the Scientific Affairs Council of the Lewy Body Dementia Association and the Editorial Board of the American Academy of Neurology’s Brain and Life. She has provided educational content for UpToDate. S.M.M. is the secretary-treasurer elect of the American Association for Geriatric Psychiatry, and has provided educational content for the Lewy Body Dementia Association. The remaining authors declare no conflicts of interest, (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Behavioral and psychological symptoms of dementia (BPSD), such as agitation, apathy, and psychosis, are highly prevalent and have a significant impact on patients and their care partners. The neurobiology of BPSD involves a complex interplay of structural brain changes and alterations in the neurotransmitter system. Various genetic and plasma biomarkers have also been studied. Research in BPSD has been limited by heterogeneity in the diagnostic criteria and assessment tools. As such, there have been ongoing efforts to develop a gold-standard assessment tool and diagnostic criteria. Current practice guidelines recommend nonpharmacological therapies as first-line treatments. Pharmacological options are often used when there is an insufficient response to nonpharmacological strategies, but there can be serious adverse effects with existing pharmacological agents. This has resulted in growing efforts to develop novel therapeutics with more favorable tolerability profiles, with some showing promising results. Other biological therapies, such as neurostimulation, have also demonstrated positive results. As our understanding of BPSD evolves, ongoing research efforts in treatment of BPSD are warranted in order to enhance the quality of life for patients and their care partners., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

SERPINA3, a serine protease inhibitor, is strongly associated with neuroinflammation, a typical condition of AD. Its expression is linked to microglial and astrocytic markers, suggesting it plays a significant role in modulating neuroinflammatory responses. In this study, we examined the SERPINA3 expression levels, along with CHI3L1, in various brain regions of AD patients and non-demented healthy controls (NDHC). Nineteen microarray datasets were analyzed, with brain samples stratified by sex and age from areas including the prefrontal cortex, occipital lobe, and cerebellum. Results showed that SERPINA3 was significantly highly expressed in AD patients compared to NDHCs only in males. Sex-specific differences were observed only in NDHCs, where females had higher SERPINA3 levels than males. ROC analysis suggested that SERPINA3 could be a strong marker for distinguishing AD in males but not females. In NDHCs, SERPINA3 expression correlated more strongly with age than in AD patients. In brain regions, SERPINA3 expression in NDHC females was higher across multiple areas, while in AD patients, this difference was limited to the prefrontal cortex. The most significant differences between NDHC and AD patients were found in the occipital and prefrontal regions. Furthermore, we identified a potential nuclear localization for SERPINA3, supported by immunohistochemistry analysis from The Human Protein Atlas. Correlation with neuropathological traits, including Clinical Dementia Rating (CDR) and Braak Neurofibrillary Tangle Score, showed positive significant associations between SERPINA3 and CDR in AD patients. Performing a docking analysis, we revealed an interaction region between SERPINA3 and CHI3L1 proteins, suggesting a potential role in AD. Tissue transcriptomic deconvolution analysis indicated a significant overlap between SERPINA3 expression and microglial/astrocytic signatures, suggesting that SERPINA3 plays a key role in modulating neuroinflammation in AD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nowadays, presynaptic dopaminergic positron emission tomography, which assesses deficiencies in dopamine synthesis, storage, and transport, is widely utilized for early diagnosis and differential diagnosis of parkinsonism. This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism. We conducted a thorough literature search using reputable databases such as PubMed and Web of Science. Selection criteria involved identifying peer-reviewed articles published within the last 5 years, with emphasis on their relevance to clinical applications. The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis. Moreover, when employed in conjunction with other imaging modalities and advanced analytical methods, presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker. This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion. In summary, the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials, ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)