bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical utility of 123I‐Ioflupane SPECT striatal binding for evaluating parkinsonism: a retrospective study of a dementia with Lewy bodies cohort
Authors: Maly Emily F , Leverenz James B , Lapin Brittany , Li Yadi , DiFilippo Frank A ,   U.S. Dementia with Lewy Bodies Consortium (DLBC)
Published: January 2025

AbstractBackgroundThis study set to determine if 123I‐ioflupane SPECT striatal binding ratio (SBR) correlated with parkinsonian symptoms measured on Movement Disorder Society – Unified Parkinson’s Disease Rating Scale Part III (UPDRS‐III) in a dementia with Lewy bodies (DLB) cohort and if SBR measured at baseline could predict progression of parkinsonian symptoms over 2 years.MethodsThis is a retrospective cohort study using the U.S. Dementia with Lewy Bodies Consortium (DLBC) dataset. Sample group included 54 individuals with probable DLB or mild cognitive impairment with Lewy bodies (MCI‐LB). Participants had baseline 123I‐ioflupane SPECT scan analyzed with DaTQUANT and baseline UPDRS‐III examination; a subset of 25 participants had a 24‐month UPDRS‐III examination. Mean of the left and right SBR Z‐scores for the striatum, putamen, posterior putamen, and caudate were analyzed. A subset of 45 participants had CSF tested with [Amprion] α‐synulcein seed amplification assay (SAA).ResultsMultivariable linear regression models were used to predict 54 participants’ UPDRS‐III at baseline; this showed baseline SBRs are significant predictors of baseline UPDRS‐III scores with the caudate SBR having the strongest correlation (p=0.005). Multivariable linear regression models were used to predict 25 participants’ UPDRS‐III score at 24‐months; this showed baseline SBRs are significant predictors of 24‐month UPDRS‐III scores with the caudate SBR having the strongest correlation (p=0.009). When adjusting for baseline UPDRS‐III scores, SBRs are no longer significant predictors of 24‐month UPDRS‐III scores (p=0.36). When a multivariable logistic regression model was used to predict meaningful worsening in UPDRS‐III from baseline to 24‐months (defined as worsening by ≥ +5 points) the relationship was not significant (AUC=0.53). A sub‐analysis of the 45 participants with α‐synulcein SAA showed that presence α‐synulcein was associated with higher UPDRS‐III scores and lower SBRs.ConclusionFindings reveal a significant relationship between 123I‐ioflupane SPECT SBRs and motor parkinsonism in DLB as measured on UPDRS‐III. In DLB, 123I‐ioflupane SPECT scan, at time of diagnosis, could be used to confirm underlying dopamine deficiency in the context of clinical parkinsonism. Findings suggest baseline 123I‐ioflupane SPECT SBRs do not add value beyond baseline UPDRS‐III in predicting clinical progression of parkinsonism in 2 years.
Functional blocking of Varicella Zoster Virus prevents acquisition of Alzheimer’s disease‐like characteristics induced by reactivation of quiescent Herpes Simplex Virus Type 1
Authors: Cairns Dana M , Itzhaki Ruth F , Kaplan David L 
Published: January 2025

AbstractBackgroundHallmark features of AD are well defined, however, the generation of in vitro models of sporadic AD poses a significant challenge due to the complex, undefined etiology and slow progression of this disease. Herpes simplex virus type I (HSV‐1) is a pathogen that is gaining increasing attention as a potential causative agent in AD pathogenesis. HSV‐1 is a DNA virus that typically resides throughout the peripheral nervous system in a latent state. We have previously shown that HSV‐1 infection of human induced neural stem cells (hiNSCs) robustly mimic human disease with amyloid plaque–like formations, P‐tau accumulation, reactive gliosis, neuroinflammation, and diminished neural network functionality; completely in the absence of any exogenous mediators of AD. Further, we have demonstrated that quiescent HSV‐1 can be reactivated by various mechanisms, which also leads to AD‐like phenotypes. Varicella zoster virus (VZV) has been implicated in Alzheimer’s disease (AD), and vaccination against shingles, caused by VZV, has been found to decrease the risk of AD/dementia. Previous work in our lab demonstrated that hiNSCs infected with VZV did not show the main AD characteristics, Abeta and P‐tau accumulation, which HSV‐1 does cause, but did show gliosis and increased levels of pro‐inflammatory cytokines, suggesting that VZV’s action relating to AD/dementia is indirect. Strikingly, we found that VZV infection of cells quiescently infected with HSV‐1 causes reactivation of HSV‐1 and consequent AD‐like changes, including Abeta and P‐tau accumulation.MethodsGiven the established efficacy of vaccination against shingles in decreasing AD risk, we sought to determine whether neutralizing antibodies generated by vaccination, could attenuate the established effects of VZV in reactivating HSV‐1‐induced AD. We utilized hiNSCs latently infected with HSV‐1 and subsequently infected with VZV in the absence or presence of neutralizing VZV, then assessed expression of Abeta and P‐tau in vitro.ResultsWe found that neutralizing antibody against VZV attenuated VZV infection and thus reactivation of HSV‐1 and associated downstream AD‐like phenotypes in hiNSCs.ConclusionsThese findings may provide mechanistic insight into the epidemiological evidence that VZV vaccination provides neuroprotection against AD/dementia.
The Sustainable Personalised Interventions for Cognition, Care, and Engagement (SPICE) Program: Interim analysis of a twelve week multicomponent intervention for people with dementia and care partners
Authors: D'Cunha Nathan M , Mitterfellner Rachael , Griffin Julie , Wiseman Lara , Isbel Stephen , Bail Kasia , Walker Ian , De Silva Sanduni , Whitting Sarah , Holloway Helen , Kosari Sam , Barrett Louise , Rutherford Kathleen , Bennett Michelle , Gibson Diane 
Published: January 2025

AbstractBackgroundThe Sustainable Personalised Interventions for Cognition, Care, and Engagement (SPICE) program was developed to address an identified gap in access to high‐quality integrated post‐diagnostic rehabilitation for people with dementia and their care partners in Canberra, Australia. The multicomponent intervention aims to maximise quality of life (QoL) and independence of people with dementia by increasing engagement in everyday and meaningful activities and promoting care partners' physical and mental well‐being.MethodThe SPICE program is a waiting‐list study design delivered by a multidisciplinary allied health team over twelve weeks. The five components are: 1) cognitive stimulation therapy; 2) carer support and capacity building; 3) physical activity; 4) Care of People with dementia in their Environments (COPE) program; and 5) dietary assessment and advice. Each group comprises up to seven people with dementia and their care partners. They engage in group activities twice weekly and receive the COPE program and dietary assessment and advice as a dyad. Outcome measures include QoL, neuropsychiatric symptoms, cognitive and physical function, and carer well‐being. Early feasibility of the program contributed to expansion of the study. Here, we report on the first six completed groups.ResultThirty‐eight people with dementia and 38 care partners attended group activities with 92% and 91% attendance, respectively. Participants completed 98% of COPE program appointments and 93% of dietary appointments. Pre‐ to post‐program improvements were observed in proxy‐reported QoL (p = 0.02), reduced neuropsychiatric symptoms (p<0.001) and carer distress related to these symptoms (p = 0.04), and reduced caregiving challenges (p<0.001). Both people with dementia and care partners improved in the Alternating Step Test (AST) (both; p<0.001), as did care partners in Timed Up and Go (TUG) (p = 0.04). Twenty‐six people with dementia and 26 care partners have completed follow‐up, improving from baseline to 24 weeks in self‐reported QoL of the person with dementia (p = 0.03), and reduced neuropsychiatric symptoms (p<0.01) and carer distress related to these symptoms (p = 0.02). Care partners maintained improvements in the AST (p<0.01) and TUG (p = 0.05).ConclusionInterim analysis suggests the SPICE program benefits people with dementia and their care partners. Further results are required to support continuation and expansion of the program.
Development of Individualized Cognitive Augmentation Regimen for Elderly (iCARE): Preliminary findings of a caregiver‐driven cognitive training for dementia in India
Authors: Kanmani Aparna S , Janakiprasad Keshav K , PT Sivakumar , Mathuranath PS 
Published: January 2025

AbstractBackgroundWith increased for promoting neuroplasticity in older adults through Cognitive training (CT), the study aimed to develop culturally relevant caregiver‐driven model of CT for dementia called the Individualized Cognitive Augmentation Regimen for Elderly (iCARE).MethodThe study has three phases‐1. Development Phase‐ Included a) literature review, b) item generation, c) expert rating, d) field trial (n = 3), and e) feedback and modification. The module is designed as a flip book primarily targeting eight cognitive domains. A unique method of empowering caregivers (family or professional) as co‐therapists was used to deliver the intervention on adequate receiving training.2. Pilot Phase ‐ A quasi‐experimental research design was used to recruit patients (n = 8) diagnosed with mild‐moderate dementia (DSM V criteria) from a clinical setting. The eligible participants were engaged as dyads (1 patient + 1 caregiver) and received either Treatment as usual (TAU) or iCARE program (1:1 ratio) for a duration of 5 weeks. They were assessed at three time points (baseline, post‐intervention, and 1‐month follow‐up).3. Main Phase – The modified program was administered on 32 dyads (16 Intervention, 16 TAU) meeting the inclusion and exclusion criteria using the same protocol. The NIMHANS neuropsychological battery for elderly (NNB‐E) was used to determine the neuropsychological profile of the patient along with rating scales to track cognitive symptoms, quality of life, activities of daily living, behavioural/psychological symptoms, caregiver health and burden.ResultThe study revealed positive results in task‐related performance, outcome variables, and functional changes. The neuropsychological profiles post‐iCARE demonstrated improvement in attention, working memory, fluency, verbal recognition and logical and visual memory. Compared to TAU, enhancement was noted in quality of life, independence in daily activities, and symptom severity. Caregivers also reported advancement in confidence, error detection, self‐correction, communication and insight. The caregivers' high rating for feasibility of iCARE make it suitable for Indian population. Qualitative evidences of the same shall be presented.ConclusionThe iCARE program intends to support families learn a better‐quality home‐based management of dementia. The method of using interactive materials and caregivers as active co‐therapists is recommended to address cognitive decline in dementia.
Event‐related Theta Phase Coherence differ between stable and progressive MCI: aTwo‐Year Follow‐up study
Authors: Özbek Yağmur , Yener Görsev 
Published: January 2025

AbstractBackgroundMild cognitive impairment (MCI) is viewed as a transitional stage between normal aging and Alzheimer's disease (AD), serving as a pathological precursor to AD. Longitudinal studies indicate an annual conversion rate from MCI to AD of 10‐15%. Our previous studies have shown decreased coherence values in visual event‐related slow frequency bands including theta frequency. This study aimed to compare event‐related theta inter‐trial phase coherence (ITC) in two groups of MCI, stable or progressive MCI, and cognitively unimpaired (CU) seniors, during a two‐year follow‐up.MethodOut of 33 individuals with MCI, 14 of the MCI patients progressed into AD dementia (ADD) at a two‐year follow‐up (progressive MCI: pMCI), whereas 19 MCI patients remained stable (stable MCI: sMCI). A total of 34 cognitively unimpaired (CU) seniors were included in this study. Classical visual oddball paradigm was used to elicit event‐related (ER) oscillations. Continuous Wavelet Transformation was used for intertrial phase locking (Intertrial Coherence) analyses.ResultMixed‐design ANOVA analysis showed TIME x LOCATION x GROUP interaction effect in theta ITC. Posthoc analyses indicated baseline temporal theta ITC values of CU were higher than sMCI (p = 0.028) and pMCI (p = 0.014). In addition, follow‐up measurements of central theta ITC of CU were higher than pMCI (p = 0.033), and parietal theta ITC of CU was higher than pMCI (p = 0.008) and sMCI (p = 0.002). It was found that the baseline temporal ITC values of CU (p = 0.018) and the baseline parietal theta ITC values of sMCI (p = 0.033) were higher compared to follow‐up measurements.ConclusionAmong the classical frequency bands, the stimulus‐locked ER theta phase reflects best about temporal processes of cortical functions for the MCI patients who convert to dementia. Furthermore, the increased ER theta coherence at the stable MCI level returns to the normal values at the later stages of MCI (pMCI). Our findings are in line with the hyperconnectivity seen at the stable MCI stage, even before becoming progressive MCI. Theta ITC may provide electrophysiological cues for displaying clinical stages during MCI period.
Association of Alzheimer’s disease polygenic risk score with concussion severity and recovery metrics
Authors: Dybing Kaitlyn M , McAllister Thomas W , Wu Yu‐Chien , McDonald Brenna C. , McCrea Michael A. , Broglio Steven P. , Pasquina Paul F. , Brooks M. Alison , Mihalik Jason P. , Guskiewicz Kevin M , Giza Christopher C. , Goldman Joshua , Duma Stefan , Rowson Steve , Svoboda Steven , Cameron Kenneth L. , Houston Megan N. , Campbell Darren E. , McGinty Gerald , Jackson Jonathan , Risacher Shannon L. , Saykin Andrew J. , Nudelman Kelly N. 
Published: January 2025

AbstractBackgroundShared genetic risk between Alzheimer’s disease (AD) and concussion may help explain the association between concussion and elevated risk for dementia. However, there has been little investigation into whether AD risk genes also associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate associations between AD genetic risk and concussion severity/recovery in the NCAA‐DoD Grand Alliance CARE Consortium (CARE) dataset.MethodThere were 1,917 injuries in the dataset upon project initiation. After removing repeated injuries, related participants, and those without genetic/outcome data, we had 931 participants. Outcomes were number of days to return to play (RTP) as a recovery measure, and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated PRS using a published score (de Rojas et al., 2021) and performed a linear regression (MLR) of RTP by PRS in normal (<24 days) and long (>24 days) RTP subgroups. We then compared severity measures by PRS using MLR. Next, we used t‐tests to examine outcomes by APOE genotype in military and civilian subgroups. We also performed chi‐squared tests of RTP category (normal vs. long) by APOE genotype. Finally, we analyzed outcomes by PRS in European or African genetic ancestry subgroups using MLR.ResultHigher PRS was associated with longer injury to RTP interval in the normal RTP (<24 days) subgroup (estimate = 0.0412, SE = 0.182, p = 0.0237). 1 SD increase in PRS resulted in a 0.412 day (9.89 hours) increase to the interval. This may be clinically meaningful in the collegiate athlete environment. We did not identify any other significant differences.ConclusionOur preliminary results provide limited evidence for an impact of AD PRS on concussion recovery, though the pattern was inconsistent and its clinical significance is uncertain. Future studies should attempt to replicate these findings in larger samples with longer follow‐up using PRS calculated from multiple/diverse populations, which will be especially relevant for diverse datasets like CARE.
Brain Banking in the United States and Europe: Importance, Challenges, and Future Trends
Authors: Danner Benjamin , Gonzalez Angelique D. , Corbett William Cole , Alhneif Mohammad , Etemadmoghadam Shahroo , Parker‐Garza Julie , Flanagan Margaret E 
Published: January 2025

AbstractBackgroundIn recent years, brain banks have become a valuable resource for examining the molecular underpinnings of various neurological and psychological disorders such as Alzheimer’s disease and Parkinson’s disease; however, the availability of brain tissue has significantly declined. Proper collection, preparation, and preservation of post‐mortem autopsy tissue are essential for optimal downstream brain tissue distribution and experimentation. Collaborations between brain banks through larger networks such as NeuroBioBank with centralized sample request mechanisms promote tissue distribution where brain donations are disproportionately lower. These collaborations would also help standardize the donation and sample preparation processes and enable the distribution of knowledge and information amongst neuroscientists. Implementing ethical measures during donation enhances the responsible conduct of scientific studies and cultivates trust among donors. Education and outreach programs that foster collaboration between hospitals, nursing homes, neuropathologists, and other research scientists can alleviate concerns among potential brain donors. Furthermore, ensuring that biorepositories accurately reflect the true demographics of communities will result in research data that reliably represents populations. Therefore, there is a need for initiatives to enhance the sustainability and efficacy of brain banks, fostering an environment that aligns with the evolving needs of scientists and researchers.MethodThis review involved a comprehensive search of Google, Google Scholar, and PubMed databases. Relevant English articles and information from websites pertaining to brain banking in the United States and Europe were extracted for thorough examination, up until November 2023.ResultBrain autopsy rates have had a steady decline from 41.1% in 1964 to less than 5% in many hospitals today. Additionally, published cost estimates of collecting a postmortem brain approximate the cost to be between $10,000 and $30,000 USD. With brain tissue scarcity posing an utmost problem to many neuropathologists and scientists, increasing standard operating procedures, centralization of Brain banks will serve to combat the decline.ConclusionSuccessful implementation of these initiatives, such as enhancing collaboration between intra‐institutional and inter‐institutional brain banks alongside integration of innovative technologies and proactive efforts to improve brain donations and storage will grant scientists improved access to brain tissue. This will then facilitate a deeper understanding of the neurological diseases that impact millions.
Connectivity to epicenters of tau accumulation contributes to regional synaptic loss in Alzheimer’s disease
Authors: Luan Ying , Wang Weiyi , Guan Yihui , Franzmeier Nicolai , Xie Fang , Ewers Michael 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is associated with substantial synaptic loss potentially due to synaptotoxicity of fibrillar tau, but the association between tau deposition and synaptic loss remains unclear. Based on previous observations that pathology spreads preferentially between closely connected regions, we tested in the current multi‐PET tracer study the hypothesis that synaptic loss propagates to regions closely connected to epicenters of high tau accumulation.MethodWe assessed 18F‐SynVesT‐1 PET as a measure of synaptic vesicle glycoprotein 2A (SV2A), and 18F‐flortaucipir tau‐PET in fourty‐five 18F‐florbetapir‐PET‐positive (Aβ+) subjects with MCI or AD dementia, and 23 cognitivly normal (CN) Aβ‐ controls. All PET scans were spatially normalized and parcellated into 200 ROIs. Adopting our previously established connectivity‐based prediction model (Franzmeier et al. Nat Commun 2020), we computed tau‐epicenter connectivity maps by projecting regions of highest tau‐PET SUVR (top 10% of group‐average tau‐PET ROIs) onto a normative resting‐state fMRI derived connectivity template from the Human Connectome Project. The tau‐epicenter connectivity map was projected onto the group‐average synaptic PET ROI w‐scores (standardized SUVR difference between Aβ+ vs Aβ‐ group) to test in linear regression analysis, epicenter connectivity as a predictor of synaptic PET w‐scores in connected ROIs. As a control, we conducted an additional regression analysis, using this time connectivity to cold spots of tau‐accumulation (10% of ROI with lowest tau‐PET uptake) instead of epicenter‐connectivity as a predictor. We repeated the analyses at the subject level, controlling for the effect of age, gender, clinical diagnosis and global amyloid‐PET uptake.ResultHigher functional connectivity to the tau‐epicenter was associated with lower synaptic PET binding in the connected ROIs (β = ‐0.380, p < 0.001, Figure 1A). In contrast, functional connectivity to the tau coldspot ROIs was associated with more preserved synaptic PET binding in the connected ROIs (β = 0.396, p < 0.001, Figure 1B). Subject‐level analysis showed consistent findings (Figure 2 for tau‐epicenters).ConclusionSynaptic loss in AD occurs in a connectivity‐dependent manner, where closer functional connectivity to regions of high tau is associated with stronger loss in synaptic PET. Putative underlying mechanisms are the higher tau in tau‐epicenter connected regions or functional decline in the connected regions.
Relationships Between Retinal Amyloid Imaging and Amyloid PET in the A4 Trial
Authors: Rissman Robert A. , Ngolab Jennifer , Donohue Michael C. , Belsha Alison , Salazar Jennifer , Cohen Paula , Jaiswal Sandhya , Tan Veasna , Aggarwal Neelum T. , Alber Jessica , Johnson Ken , Jicha Gregory A , van Dyck Christopher H. , Lah James J. , Salloway Stephen , Rafii Michael , Aisen Paul S. S. , Sperling Reisa A 
Published: January 2025

AbstractBackgroundAlterations to the retina manifest in patients diagnosed with neurodegenerative diseases such as Alzheimer’s disease (AD). Retinal imaging techniques open the possibility for non‐invasive evaluation of AD pathology. Clinically AD diagnosed patients exhibit retinal amyloid deposits. Few studies monitoring preclinical individuals exist, limiting the assessment of the feasibility of retinal imaging as a biomarker for early‐stage AD risk detection.MethodWe compared retinal and cerebral amyloid in clinically normal individuals who screened positive for amyloid through positron emission tomography (PET) from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) as well as a companion cohort of individuals who were negative on amyloid by amyloid PET in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. We quantified the number of curcumin‐positive fluorescent retinal spots from a small subset of participants from both studies to determine retinal amyloid deposition at baseline.ResultParticipants from the A4 trial exhibited a greater number of retinal spots compared to those from the LEARN study. We report a positive correlation between retinal spots and brain amyloid, as measured by the standardized uptake value ratio (SUVr).ConclusionThe results of this small pilot study support the use of retinal fundus imaging for detecting amyloid deposition that is correlated with brain amyloid PET SUVr. A larger sample set is under analysis currently to fully ascertain the relationship between amyloid PET and retinal amyloid both cross‐sectionally and longitudinally.