bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of socioeconomic deprivation on long‐term outcomes in Parkinson’s disease and frontotemporal lobar degeneration syndromes
Authors: Dreyer Anna Jane , Murley Alexander G , Coyle‐Gilchrist Ian , Stockton Katherine , Holland Negin , Camacho Marta , Rouse Matthew A , Naessens Michelle , Brayne Carol , Barker Roger A , Williams‐Gray Caroline H. , Rowe James B 
Published: January 2025

AbstractBackgroundSocioeconomic deprivation has been associated with shorter survival and an earlier loss of functional independence in patients with Alzheimer’s disease and dementia. However, the effect of deprivation on outcomes in Parkinson’s disease (PD) and syndromes associated with frontotemporal lobar degeneration (FTLD) are largely unknown. Prognosis in these neurodegenerative diseases is variable and difficult to predict despite multiple known sociodemographic, clinical and genetic predictors. Using data from three long‐term prospective incident cohorts in the UK, we conducted a survival analysis to investigate the association of the deprivation in one’s residential area with outcomes after symptom onset and diagnosis.MethodWithin known geographical settings patients with FTLD‐associated syndromes (bvFTD, PPA, PSP, CBS; N = 283) were recruited in three waves (2013‐2014, 2017‐2018, 2021‐2022) as part of PIPPIN. Similarly, patients with PD were recruited as part of CamPaIGN (N = 140) from 2000‐2002, and PICNICS (N = 280) from 2008‐2013. The Index of Multiple Deprivation (IMD) centile was assigned to each participant according to their residence at the time of diagnosis and dates of care home admission and death recorded from NHS records. Using Cox proportional hazards regression, we investigated the univariable and multivariable associations between IMD and (1) absolute survival (time to death) (2) independent survival (time to care home admission/death) (3) remaining cognitively healthy in PD (time to dementia diagnosis).ResultIMD did not predict absolute or independent survival, in any of the three cohorts, in univariable or multivariable analyses. In univariable models, IMD predicted time to PD dementia diagnosis in PICNICS, but not in the other cohorts. Multivariable models showed that poorer outcomes were associated with sociodemographic (older age, being male), clinical (disease severity, cognitive deficits, depression, FTLD diagnosis) and genetic variables (APOE, GBA), but not IMD.ConclusionTo live in an area of higher socioeconomic deprivation is not associated with poorer long‐term survival in patients with FTLD‐associated syndromes or PD. In patients with PD, living in an area of high deprivation predicted shorter time to dementia diagnosis. These reassuring results might reflect universal healthcare coverage (i.e., NHS), with specialist services for patients able to mitigate deprivation effects.
Evaluating the potential of teleneurology in a low‐resource setting for dementia: An exploratory study on patient and healthcare provider satisfaction
Authors: Alexander Pullumpallil Thomas , Ansari Mohammad Farhan , Rao Girish N , Arshad Faheem , Menon Deepak , Thomas Priya Treesa , Ramakrishnan Subasree , Parthasarathy Rajani , Alladi Suvarna 
Published: January 2025

AbstractBackground and ObjectivesTelemedicine, including teleneurology, has emerged as a valuable tool for providing healthcare services remotely, particularly in situations where distance plays a critical role. Teleneurology has the potential to increase access to care, improve patient outcomes, and reduce healthcare costs, especially for patients in rural and underserved areas. We aimed to investigate patients and health care providers satisfaction with teleneurology for dementia.MethodsWe recruited 15 patients with dementia as a part of a public health initiative on Brain Health in the state of Karnataka in India. Patients resided across different districts of the state and had undergone an initial consultation at the specialist centre. Follow up teleconsultations were conducted using the Zoom Video Conference application and included a brief neurological examination. Patient and/or caregiver satisfaction was assessed using Telemedicine Satisfaction Questionnaire (TSQ) and healthcare provider satisfaction was assessed using Patient and Physician Satisfaction with Monitoring Questionnaire (PPSM).ResultsOf the 15 patients with dementia enrolled in the study, mean age of the cohort was 65 years. All 15 patients [8 men] or caregivers completed the Teleneurology Satisfaction Questionnaire (TSQ), yielding a mean score of 4.47±0.41. The mean duration of teleconsultation was 43 minutes. Additionally, the Patient Perception of Satisfaction with Method (PPSM) questionnaire was completed by the neurologist for all 15 patients, resulting in a mean score of 4.33±0.44. Among these patients, 12 consultations were initiated by a primary care physician, and all of them completed the PPSM questionnaire, which had a mean score of 4.04±0.51. Paired patient and neurologist agreement was 60% for quality of care provided, 98% for time saving benefit and 95% for willingness for future use.DiscussionOverall, patients or their caregivers expressed satisfaction with the quality of care provided through teleneurology and agreed that it was comparable to face‐to‐face encounters. Primary care physicians also reported positive experiences with teleneurology, including a good understanding of patients' health status and the belief that teleneurology was a valuable addition to regular care. Both patients or caregivers and neurologists agreed for the quality of care provided, the time saving benefits and the willingness for future use of teleneurology.
Longitudinal neurodegeneration in relation to amyloid pathology among cognitively unimpaired individuals
Authors: Stephenson Henry Gilreath , Betthauser Tobey J. , Hulle Carol A. Van , Du Lianlian , Langhough Rebecca E. , Jonaitis Erin M. , Kollmorgen Gwendlyn , Quijano‐Rubio Clara , Chin Nathaniel A. , Okonkwo Ozioma C , Carlsson Cynthia M. , Asthana Sanjay , Christian Bradley T. , Johnson Sterling C. , Blennow Kaj , Zetterberg Henrik , Bendlin Barbara B. 
Published: January 2025

AbstractBackgroundThe timing of neurodegeneration in relation to the onset of Alzheimer’s disease pathology is not fully known. This study examined the association of longitudinal atrophy derived from T1‐weighted MRI with 1) cerebrospinal fluid (CSF) amyloid‐tau (AT) groupings and 2) Pittsburgh compound B (PiB) PET‐derived estimates of amyloid duration among cognitively unimpaired (CU) individuals.MethodCU participants in the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center (N = 297) underwent longitudinal MRI, APOE genotyping, and lumbar puncture to determine CSF Aβ42/40 (A) and pTau181 (T) concentration at baseline using in‐house cutoffs. CSF measurements were performed using the NeuroToolKit, a panel of robust prototype biomarker assays (Roche Diagnostics International Ltd). Image segmentation was performed using a longitudinal pipeline in SPM12. Grey matter volumes from AD‐associated regions (adjusted for intracranial volume) were z‐scored according to age‐associated predictions from a robust longitudinal A‐T‐/APOE4‐/CU control group. Differences in longitudinal atrophy relative to controls were tested in linear mixed‐effects models using contrasts between A+T‐ and A+T+ groups and A‐T‐ controls and interactions with time (years from baseline). In the PiB PET subset, sampled iterative local approximation was used to estimate time‐to‐positivity at baseline relative to a PiB DVR threshold of 1.16. CSF A+ individuals were grouped as CSF A+ only, early PiB+ (PiB+ <= 5 years), and established PiB+ (PiB+ > 5 years). Differences in longitudinal atrophy were tested with A+ group/A‐T‐ contrasts and interactions with time. All analyses were FDR‐corrected. See Table 1 and Figure 1 for participant characteristics and model details.ResultBased on CSF assays, both A+ groups showed longitudinal atrophy relative to controls in a majority of ROIs, suggesting that A+, regardless of pTau+, is associated with neurodegeneration. Further analysis incorporating PET showed that CSF A+ in the absence of PiB+ was not associated with atrophy, but early PiB+ was associated with atrophy in medial temporal ROIs and precuneus. The largest and most widespread atrophy was observed in the established PiB+ group (Figure 2).ConclusionNeurodegeneration appears to begin soon after the onset of PET‐measurable amyloid‐positivity. Clinical intervention at the earliest signs of amyloid deposition may be needed to delay neurodegeneration.
Altered Regional and Whole‐Brain Excitation/Inhibition Balance Correlates with Alzheimer's Disease Risk Factors
Authors: Burns Andrew P , Fortel Igor , Bendlin Barbara B. , Zhan Liang , Leow Alex 
Published: January 2025

AbstractBackgroundResearch indicates that the brain operates near a critical excitation/inhibition (E/I) balance point, which, when disrupted, correlates with Alzheimer’s Disease (AD) risk factors such as APOE genotype and sex. Utilizing our established multimodal imaging method (Fortel, Igor, et al. Network Neuroscience 6.2 (2022): 420‐444.), we investigated the E/I balance in cognitively normal and impaired individuals, focusing on factors like APOE status, amyloid status, age, sex, and dementia ratings.MethodWe analyzed 593 participants, aged 43‐92 (m = 62), including 495 cognitively intact and 98 impaired individuals, through 871 E/I ratio assessments (207 had multiple assessments). Participants underwent T1‐weighted, resting‐state, and diffusion‐weighted MRI to construct hybrid resting state structural connectomes for 105 regions using a recent multimodal connectome technique to detect whole‐brain and region‐specific E/I ratios. We employed two linear mixed models to correlate E/I ratios with age, sex, e4+/e4‐ status (binary) or APOE‐npscore (continuous), whole‐brain amyloid status (binary), and clinical dementia rating, adjusting for multiple comparisons. Patient IDs were used as random effects in the models to account for repeated measurements, with no interaction effects included. All imaging and variables were obtained from OASIS‐3: Longitudinal Multimodal Neuroimaging: Principal Investigators: T. Benzinger, D. Marcus, J. Morris; NIH P30 AG066444, P50 AG00561, P30 NS09857781, P01 AG026276, P01 AG003991, R01 AG043434, UL1 TR000448, R01 EB009352. AV‐45 doses were provided by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly.ResultBoth linear mixed models identified 26, significant E/I variations across the brain related to age, clinical dementia rating, and sex. Specific AD‐relevant regions such as the hippocampus and amygdala (Figure 1) show notable E/I changes. Whole brain E/I was negatively correlated with the APOE‐ε4 allele in the binary APOE status model but not in the continuous APOE‐npscore model.ConclusionWe demonstrated significant E/I ratio alterations in the whole brain and known AD relevant regions, such as the hippocampus and amygdala, against the largest risk factor of AD (age), clinical dementia rating, and binary APOE status. Our findings are consistent with past studies exhibiting correlations between altered E/I metrics and known AD risk factors.
Quantitative transport mapping estimated blood flow velocity is more sensitive to the perfusion change in Alzheimer's disease than the conventional cerebral blood flow, estimated from multiple delay arterial spin labeling
Authors: Zhou Liangdong , Guo Yihao , Li Yi , Wang Yi , Liu Tao , Chen Huijuan , Huang Weiyuan , Chiang Gloria , de Leon Mony J. , Chen Feng 
Published: January 2025

AbstractBackgroundQuantitative transport mapping (QTM) has been developed for estimation of blood flow velocity with 4D dynamic tracer concentration data (Zhou et. al., Magn. Reson. Med. 2021;85: 2247–2262; Zhang et. al., Magnetic Resonance Imaging 2022; 86: 86–93). We investigated the QTM and CBF in human brain for Alzheimer's disease using multiple post‐labeling delay arterial spin labeling (mPLD‐ASL) MRI.MethodA total of 131 subjects (28 AD, 82 patients with mild cognitive impairment (MCI), and 21 normal controls (NC)) were prospectively recruited in this study. All participants underwent magnetic resonance imaging (MRI) examination and neuropsychological evaluation. CBF and QTM maps were computed from ASL with multiple PLD (Wang et al Neuroimage: Clinical 2013; 3:1‐7). Group differences of regional CBF and QTM analysis were performed and compared. The associations between perfusion and cognition were assessed.ResultRegional analysis showed decreased QTM value in occipital lobe, and hippocampus in MCI compared with NC as shown in Figure 1 (D)‐(F). CBF only decreases in AD patients compared to NC in cerebral cortex and hippocampus and was not able to distinguish MCI and NC as shown in Figure 1 (A)‐(C). CBF and QTM in hippocampus were both positively correlated with cognition, including global cognition, memory, executive function, and language function.ConclusionThis study demonstrated a reduced QTM of occipital lobe and hippocampus in MCI compared with NC, suggesting QTM as a potential early biomarker for AD. QTM in the hippocampus are correlated with cognitive deterioration. These findings contribute to a clear comprehension of perfusion change, glymphatic clearance deficit and cognitive decline in AD. QTM performs superior to CBF in distinguishing MCI and NC could be due to its accurate biophysical nature where arterial input function (AIF) is not required, and local mass conservation is satisfied. Global AIF used in CBF estimation could be not sufficiently sensitive to the physiological change at the early stage of AD.
Genetic contribution to the sex differences of tau pathologies in Alzheimer’s disease –APOE and beyond
Authors: Wang Yi‐Ting , Therriault Joseph , Rahmouni Nesrine , Macedo Arthur C. , Servaes Stijn , Arias Jaime Fernandez , Mathotaarachchi Sulantha , Stevenson Jenna , Gauthier Serge , Rosa‐Neto Pedro ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) disproportionately impacts females, who exhibit a higher tau load compared to males. Existing literature suggests that biological sex may alter the impact of APOE on tau pathology in AD. Nevertheless, the genetic factors contributing to sex differences in AD tau pathology, beyond the influence of APOE, have been minimally investigated.MethodsThis study included 2 well‐characterized AD cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD, n=359) cohort and the ADNI cohort (n=283). All participants underwent APOE genotyping and PET imaging with radioligands targeting Aβ plaques and tau tangles respectively. Polygenic hazard score (PHS) was computed using 31 AD‐associated SNPs identified from a stepwise Cox proportional hazards model for each ADNI participant. Low and high PHS is defined as low: −1 SD, ∼16 percentile; and high: +1 SD, ∼84 percentile.ResultsSex‐disaggregated voxel‐based analyses revealed higher tau‐PET SUVRs in female subjects with APOE4 allele(s) and high PHS (Figure 1). ANOVA tests also showed a significant difference in tau load in Braak I‐II ROIs between female E4 carriers and both male E4 carriers (P<0.05) and non‐carriers (P<0.0001). To illustrate the relationship between Aβ and tau, modulating by APOE4carriage status, non‐linear Locally Weighted Scatterplot Smoothing (LOWESS) trendlines were applied, demonstrating an initial rise in tau among female E4 carriers, succeeded by male E4 carriers (Figure 2). Subsequently, linear Ordinary Least Squares (OLS) regression analyses were conducted to explore the influence of PHS on the Aβ‐tau relationship. Notably, female individuals in the high PHS group exhibited the highest tau load under a comparable Aβ load compared to other groups (Figure 2). In line with this, regression analyses unveiled a modulating effect of PHS and sex on tau load in AD‐associated regions, and this effect remained statistically significant after adjusting for APOE4 carriage status (Table 1).ConclusionsIn the trajectory of Alzheimer's disease, early‐stage tau deposition was more pronounced in female individuals with the APOE4 allele. Our findings suggest exploring the polygenic architecture aids in identifying female individuals at the highest risk of developing tau pathology. This may be valuable for stratifying AD risk and as an enrichment strategy in clinical trials.
Providers’ Experiences Implementing Cognitive Care Planning: Barriers and Facilitators
Authors: Britt Katherine Carroll , Xiao Xaviera , Sun Kevin H , Huang Bin 
Published: January 2025

AbstractBackgroundCognitive care planning—the process of regularly and systematically assessing patient needs and documenting recommendations to address them—improves health and quality of life among patients with cognitive impairments, like Alzheimer’s disease and related dementias (ADRD). A cognitive care plan may promote physical exercise, social engagement, healthier eating, medication recommendations, and overall improvement in care management (e.g., advance care planning), which translates to lower health facility use and better quality of life. As dementia is progressive, even short‐term improvements in quality of life, emotional health, and resource use can significantly alleviate the disease burden. With limited pharmaceutical treatments, cognitive care planning is likely to remain one of the most effective ways to promote care among patients with ADRD. Despite significant potential benefits for patients and caregivers, formal and individualized cognitive care planning remains underutilized.MethodWe conducted a qualitative study exploring providers’ perceptions and experiences implementing cognitive care planning in their practice. A purposive sample of 8 primary care providers actively caring for older adults including patients with ADRD participated in semi‐structured teleconference interviews. Iterative inductive content analysis was used to analyze data.ResultOur preliminary results indicate several barriers and facilitators for implementing cognitive care planning into practice by providers. Providers reported some familiarity with general cognitive care and assessment but lacked a clear systematic approach and thorough understanding of the cognitive care planning process and steps. Across patient‐ and caregiver‐related, organization‐related, clinical care team‐related, and provider‐related focused areas, we identified five categories: (1) perceptions (buy‐in or reluctance), (2) family presence (context, support, communication, provider‐patient relationship), (3) logistics and priorities (time, schedule, staffing, priorities), (4) structure/systemized approach (standardization, templates, clear roles, referrals), and (5) experience and training (confidence or unfamiliarity).ConclusionProviders expressed the value of a structured approach for successfully implementing cognitive care planning. Buy‐in at multiple levels (patient, caregiver, organization, and clinical team) may prompt prioritizing this care approach in practice to restructure the assessment process for older adults. In addition, caregiver and family accompaniment to patient visits can increase contextual knowledge and provider communication for tailoring cognitive care plans.
Building a dementia care effectiveness trial to facilitate and anticipate widespread intervention adoption
Authors: Fortinsky Richard H , Robison Julie T 
Published: January 2025

AbstractBackgroundThis presentation maps the journey of an evidence‐based dementia care program from effectiveness trial design to adoption by policymakers as an ongoing program available to eligible older adults living at home with dementia and their care partners. Care of People with Dementia in their Environments (COPE) is a non‐pharmacologic program that seeks to maximize physical function and quality of life in people with dementia and build dementia management skills in care partners. Efficacy trial results showed that, compared to controls, people with dementia receiving COPE had greater functional independence in activities of daily living and care partners receiving COPE reported improved well‐being and increased confidence using dementia management skills.MethodsFrom 2014‐2020, COPE was tested in Connecticut, USA, using an effectiveness‐implementation hybrid design. The target population was people with dementia receiving services from Connecticut’s Medicaid‐funded home and community‐based services (HCBS) program and their care partners. Several study features were designed to anticipate the possibility that COPE might be adopted for widespread use if the study were successful. First, a translational advisory committee met annually to help guide the study and interpret findings with an eye toward offering COPE within Connecticut’s HCBS program throughout the state. Advisory committee members included leaders from Connecticut’s Medicaid program and from the state’s largest HCBS service coordination organization. Second, this service coordination organization co‐designed study recruitment procedures with the study team, including use of its electronic health record system to identify and invite people with dementia and care partners to join the study. Third, qualitative data were used to give voice to stakeholders about how well COPE was implemented within the HCBS program workflow. Fourth, extensive cost data were captured enabling economic analyses to be presented to policymakers.FindingsCare partners receiving COPE reported more improved well‐being, and total healthcare costs were lower among older adults receiving COPE, compared to those not receiving COPE.ConclusionsBased on study findings, COPE is being incorporated into Connecticut’s HCBS program pursuant to public policy opportunities that arose in the wake of the COVID pandemic, which has provided funding for a variety of new Medicaid HCBS initiatives.