bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using the Driving and Dementia Roadmap (DDR) to address the emotional impact of driving cessation and dementia
Authors: Naglie Gary , Stasiulis Elaine , Sandhu Harvir , Gallucci Christina E. , Rapoport Mark J. 
Published: June 2023

AbstractBackgroundThe emotional impact of driving cessation for people living with dementia (PWD) and their family/friend carers (FCs) can be significant, often contributing to their avoidance of this issue. In addition to the grief and anger associated with PWD’s loss of identity and independence, feelings of fear and distress can accompany PWD’s and FC’s lack of knowledge about driving cessation. In this study, we conducted an implementation evaluation of the Driving and Dementia Roadmap (DDR). The DDR is a web‐based collection of resources and tools to support PWD and FCs through the decision‐making process and transition to non‐driving, including information on managing the oft‐neglected emotional implications of stopping to drive.MethodSemi‐structured interviews were conducted with 19 Alzheimer Society (AS) staff after a three to six month period of delivering the DDR to their clients in six AS sites in four Canadian provinces. Eight PWD and 13 FCs who engaged with the DDR were also interviewed. Participants were asked about their experiences of delivering or using the DDR. An inductive thematic analysis of the data was conducted.ResultAccording to study participants, the DDR had both a direct and indirect impact on the emotional aspects of driving cessation for FCs and PWD. FCs described how the emotion content gave them insight about the grief and loss the PWD was experiencing. This understanding helped them to attend to the emotional ramifications of driving cessation and to initiate conversations about driving with compassion, empathy and patience. Indirectly, the DDR also helped PWD and FCs feel that they are not alone, thus “normalizing” driving cessation. They reported being reassured that the actions they had taken and decisions made to stop driving were appropriate. Strategies about remaining mobile also brought relief and hope that PWDs’ quality of life could be maintained once driving ceased.ConclusionBy providing resources and tools that not only directly address the emotional impact of driving cessation, but also attend to other aspects of managing the decision‐making and transition to non‐driving, the DDR has the potential to lessen the associated grief, fear and distress often experienced by PWD and FCs.
Pathways to diagnosis: The lived experiences of obtaining a dementia diagnosis among care partners
Authors: Xu Hanzhang , Fish Laura J , Nohria Raman , Christy Jacob , Falkovic Margaret , Dupre Matthew E. , Anderson Ruth , Ostbye Truls 
Published: June 2023

AbstractBackgroundAchieving a timely diagnosis of Alzheimer’s disease and related dementias (ADRD) has been challenging, and racial/ethnic minority older adults often have delays in their ADRD diagnoses despite having a higher disease prevalence. This qualitative study engaged care‐partners of patients to identify key barriers that they have experienced during their ADRD diagnosis process, ascertain their recommendations for addressing these barriers, and assess racial differences in the diagnosis process.MethodWe purposively sampled 11 Black and 10 White care‐partners (n = 21) of persons who were diagnosed with ADRD within the past two years. We conducted semi‐structured interviews to gather details and to identify the barriers/facilitators that they experienced. To prompt discussion, we asked participants to complete a card sort activity identifying occurrence and order of common events in the diagnosis pathway. We applied content analysis guided by life course theory to identify themes and to explore differences in diagnosis pathways between Black and White participants.ResultOverall, about 70% of care‐partners were female, age 60 (on average), and 57% were adult children of persons with ADRD. Less than 30% of Black care‐partners reported having adequate knowledge about ADRD, whereas the proportion was 60% among their White counterparts. Most often, early signs of ADRD were first noticed by care‐partners. However, some considered these signs as part of the normal aging process. Care‐partners reported visiting multiple providers along the process, and some visits were related to other conditions. Some care‐partners noted that the involvement of other family members was a barrier to the ADRD diagnosis. Most care‐partners described the diagnosis process as difficult and devastating, and Black care‐partners discussed experiencing unmet needs along the process more frequently than White care partners. Some care‐partners suggested having a navigator that can walk them through the process would be helpful. They also shared that the navigator should be able to tailor services based on the needs, as each family’s situation is different.ConclusionThis study highlights the unmet needs experienced by care partners along the diagnosis process of ADRD. Black and White differences were also identified. More person‐centered care coordination programs are needed to promote early identification of ADRD.
Relative importance of multimodal risk factors to discriminate memory trajectories: Similarities and differences across ethnoracial groups in cognitively normal older adults
Authors: Sapkota Shraddha , Maillard Pauline , Fletcher Evan M , Harvey Danielle J. , Whitmer Rachel A. , Olichney John M. , Jin Lee‐Way , Decarli Charles 
Published: June 2023

AbstractBackgroundInequalities in dementia incidence and heterogeneities observed on memory decline are present across ethnic/racial groups. Research suggests that inequities in risk/protective factors contribute towards these differences. We examine risk factors across multiple domains to identify those that best discriminate differences in memory trajectories across ethnoracial groups.MethodWe used an ethnoracially diverse longitudinal cohort of cognitively normal older adults (n = 299; mean age = 73.47 (6.90) years; 63.9% female) from the University of California, Davis‐Alzheimer’s Disease Research Center. First, we applied latent class growth analysis to objectively classify memory trajectories into distinct latent groups across a maximum of 10 follow‐ups. Second, we used random forest analyses (RFA) to examine relative importance of 22 risk/protective factors from seven domains (demographic, genetic, brain morphometry, plasma and functional biomarkers, psychological and lifestyle factors) to discriminate low/high memory performers as stratified by three ethnoracial groups (African Americans [AA; n = 111]; Hispanics [n = 108], Whites [n = 66]).ResultFirst, we observed that four latent classes (low, intermediate, high, very high) best represented memory trajectories (Figure 1). Second, for our RFA analyses, we collapsed low and intermediate groups to a low group (n = 136; 40.4% AA, 25.6% Hispanics, 28.8% Whites), and high and very high to a high performing group (n = 148; 34.6% AA, 50% Hispanics, 15.4% Whites). High memory class was predicted (Figure 2) in AA by lower smoking years, lower Functional Assessment Questionnaire (FAQ), younger age, higher education, lower neurofilament light (NfL), Apolipoprotein E non‐carriers, low neuropsychiatric inventory (NPI) severity, men, and higher hippocampal volume (AUC = 0.73); in Hispanics with men, lower FAQ, lower Geriatric Depression Scale (GDS), smaller third ventricle, larger hippocampal volume, lower NPI severity, smaller lateral ventricle, and lower NfL (AUC = 0.86); and in Whites, with lower FAQ, higher education, higher alcohol use frequency, lower NfL, lower GDS, smaller lateral ventricles, and low white matter hyperintensities (AUC = 0.82).ConclusionWe observed similarities and differences in predictors to discriminate low versus high memory performers in three ethnoracial groups. Identifying relative importance of risk factors will promote the integration of multimodal risk factors across ethnoracial groups to develop novel and complex risk profiles leading to early detection and identification of asymptomatic or preclinical older adults.
Correlation between inflammatory markers with cognitive function in coronavirus disease‐19 (COVID‐19) patients
Authors: Fitri Fasihah Irfani , Darman Winda Rahmah , Ritarwan Kiking 
Published: June 2023

AbstractBackgroundCoronavirus disease‐2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and remains an ongoing global pandemic. Although it mainly affects the respiratory system, its manifestation in other organs including nervous system has been increasingly recognized. Previous studies have shown the association between several inflammatory markers with disease severity and mortality in COVID‐19 patients but their association with cognitive function remains unclear. This study aimed to determine the correlation between inflammatory markers with cognitive function in COVID‐19 patients.MethodThis was a cross‐sectional study involving COVID‐19 patients during admission using consecutive sampling method in Adam Malik General Hospital Medan Indonesia. Cognitive function was assessed in several domains using Forward Digit Span (FDS), Backward Digit Span (BDS), and Trail Making Tests A and B (TMT‐A and TMT‐B), to assess attention, working memory and executive function, respectively. We measured neutrophil to lymphocyte ratio (NLR,) C‐reactive protein (CRP), D‐dimer, and ferritin serum levels as inflammatory markers.ResultThis study involved 40 COVID‐19 patients consisting of 13 (32.5%) males and 27 (67.5%) females, the median age value of the patients was 39.5(19‐65) years. We found that higher ferritin level was correlated with worse FDS and BDS scores (r = ‐0.365 p = 0.020 and r = ‐0.408 p = 0.009, respectively)and that d‐dimer level was significantly correlated with worse BDS score (r = ‐0.369 p = 0.019). Higher D‐dimer and ferritin levels were also significantly correlated with longer time of completion of TMT‐B (r = 0.363 p = 0.022 and r = 0.433 p = 0.005, respectively) and higher ferritin level was also correlated with longer time of completion of TMT‐A (r = 0.438 p = 0.005). There were no significant correlation between NLR and CRP level with cognitive function.ConclusionHigher inflammatory markers were correlated with attention, working memory and executive function in COVID‐19 patients.
Quantifying neuronal biomarkers in aqueous humor in individuals undergoing routine cataract surgery and correlating with age and cognition
Authors: Robbins Cason B , Wisely C. Ellis , Singh Pali P , Kim Terry , Grewal Dilraj S , Fekrat Sharon 
Published: June 2023

AbstractBackgroundPlasma and cerebrospinal fluid (CSF) levels of neuronal biomarkers have been associated with Alzheimer’s disease (AD). The aqueous humor, which can be collected during routine cataract surgery, may have similar concentrations of neuronal biomarkers to CSF.MethodThis proof‐of‐concept study prospectively enrolled adults without a diagnosis of cognitive impairment undergoing cataract surgery at a tertiary academic medical center. Participants underwent Montreal Cognitive Assessment (MoCA blind version 7.1, “abnormal” < 18) at the time of study enrollment. Aqueous samples were collected during cataract surgery through a surgical paracentesis. Samples were analyzed using an ultrasensitive single‐molecule array (SiMoA). Assessed biomarkers included phosphorylated tau (pTau)‐181, amyloid‐beta (Aß)‐42, Aß‐40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Correlations were assessed using Spearman’s rank correlation (rho).ResultSixteen eyes of 16 patients (average MoCA 19.2) underwent aqueous sampling to assess pTau‐181 and 7 eyes of 7 separate patients (average MoCA 20.0) underwent aqueous and plasma sampling to assess Aß‐42, Aß‐40, NfL, and GFAP. Aqueous pTau‐181 increased with increasing age (rho = 0.67, p = 0.0046). No aqueous or plasma biomarkers were significantly correlated with MoCA scores (all p > 0.05). Aqueous and plasma levels of biomarkers were not significantly correlated.ConclusionNeuronal biomarkers are measurable in aqueous humor using SiMoA analysis; however, these biomarkers did not significantly correlate with MoCA scores in a cognitively normal population. Further study in individuals with a known diagnosis of Alzheimer’s disease or mild cognitive impairment is indicated.
Early structural brain markers for Alzheimer’s Disease in women: Brain‐behaviour relationships after ovarian removal
Authors: Brown Alana , Gravelsins Laura , Almey Anne , Gervais Nicole J , Duchesne Annie , Rieck Jenny , Reuben Rebekah , Karkaby Laurice , Perovic Mateja , Witt Suzanne Tyson , Classon Elisabeth , Lykke Nina , Theodorsson Elvar , Ernerudh Jan , Lundqvist Elisabeth Åvall , Kjølhede Preben , Morrison India , Novembre Giovanni , Engström Maria , Bernardini Marcus , Foulkes William , Rajah Natasha , Grady Cheryl , Einstein Gillian 
Published: June 2023

AbstractBackgroundWomen with bilateral salpingo‐oophorectomy (BSO; removal of ovaries and fallopian tubes) prior to age 50 have increased Alzheimer’s disease (AD) risk (Rocca et al., 2007), but the neural mechanisms for this are unclear. Abilities involving manipulation/maintenance aspects of working memory (WM) decline post‐BSO, and this effect may be reduced by estradiol‐based hormone therapy (ET; Gervais et al., 2020). Considering decline in manipulation/maintenance aspects of WM in AD (Germano & Kinsella, 2005), we aimed to understand the relationships between brain structure and WM after BSO.MethodWomen with BSO taking ET (BSO+ET: M±SDage = 44.92±5.11, n = 26) or not taking ET (BSO: M±SDage = 45.62±5.04, n = 26) were compared to age‐matched premenopausal controls (AMC: M±SDage = 43.71±2.92, n = 42) recruited from Toronto, Montreal, and Linköping. T1‐weighted structural magnetic resonance imaging scans were acquired. Voxel‐based morphometry measures of gray matter volume were obtained (CIVET pipeline, Ad‐Dab’bagh et al., 2005). Digit Span Backward (DSB) and Forward (DSF) subtests (Wechsler, 1945) were administered to assess manipulation/maintenance and updating/maintenance aspects of WM, respectively. Multivariate Behaviour Partial Least Squares (McIntosh & Lobaugh, 2004) was used to compare the correlation between performance (DSB and DSF) and volume between groups.ResultThere were no group differences in DSB/DSF total span performance. AMC did not show a significant relationship between volume and WM (Figure1A). For BSO and BSO+ET, gray matter volume in key WM regions, including bilateral supplementary motor area, inferior temporal gyrus, superior and inferior frontal gyri, left precuneus, and right cuneus, was negatively associated with DSB performance (Figure1B warm colours), while hippocampal volume was positively associated with DSB performance (Figure1B cold colours). These relationships were strong for BSO (R = ‐0.78), while BSO+ET (R = ‐0.37; moderate correlation) showed an intermediate phenotype between BSO and AMC (R = 0.14; small correlation).ConclusionManipulation/maintenance aspects of WM and regional volume relationships depended on menopause status and ET. Without ET after BSO, successful WM performance correlated more strongly with hippocampal volume, which is usually the case for high memory load WM tasks (Geva et al., 2016). Even when memory changes are undetected by standard neuropsychological tests, brain‐behaviour relationships may prove a useful tool for assessing early changes in individuals at increased AD risk.
Systems analysis of Alzheimer’s disease pathway dysregulation in human subjects is recapitulated in 3d cellular models to reveal P38 MAPK as a therapeutic target that mitigates tau pathology
Authors: Yeganeh Pourya Naderi , Kwak Sang Su , Jorfi Mehdi , Quinti Luisa , Koler Katjuša , Choi Younjung , Park Joseph , Von Maydell Djuna K , Centinbas Murat , Sadreyev Ruslan I , Tanzi Rudolph E. , Hide Winston , Kim Doo Yeon 
Published: June 2023

AbstractBackground3D human neural cell culture models of Alzheimer’s disease (AD) are valuable resources for studying AD pathogenesis mechanisms. Although our 3D models capture cellular heterogeneity and key pathogenic cascades in AD, including β‐amyloid (Aβ) accumulation and Aβ‐induced tau pathology, it is not known to what extent 3D models functionally reflect human AD pathogenesis. We address this gap by capturing functionally active AD pathways in human brain through a granular systems approach that accurately recapitulates the activity of disease‐associated pathways from afflicted brain tissues in 3D models.MethodsWe leveraged transcriptomic data to precisely determine the activity dynamics of biological pathways. We assembled transcriptomic data from AD brains and compared them with a battery of 3D models displaying a broad range of disease‐associated characteristics. Our approach discovered pathways showing concordant dysregulation patterns between human brain and disease models. We prioritized the most consistent AD‐pathways for in‐vitro therapeutic screening.ResultsOne of our 3D models has transmembrane domain APP mutations, but not PS1 mutations and exhibits an elevated Aβ42/40 ratio. It best recapitulated dysregulated AD‐pathways found in both human prefrontal and temporal cortices. Multiple pathways indicated activation of p38 MAPK signaling, coupled with broad transcriptional inactivation in AD. Cellular and biochemical validations demonstrated elevated phosphorylated‐p38 (p‐tau)/total‐p38 ratios. Treatment with a p38 MAPK inhibitor resulted in significant reduction in the total amount of tau, significant reduction in the amount of p‐tau, and suggestive reduction in p‐tau/tau ratio. Our results strongly support a critical role for p38 MAPK signaling in mediating Ab‐induced tau pathology.ConclusionsUsing human brain transcriptomes, we have introduced a broadly‐applicable systems biology approach to rapidly discover therapeutic targets in 3D models. The approach provides a granular determination of the degree to which cellular models accurately reflect dysregulated molecular pathways in afflicted brains. We have detected, validated, and targeted the activated p38 MAPK pathway in AD. We have diminished tau pathology by inhibiting p38 MAPK signaling in cellular models, suggesting that the p38 MAPK pathway is a potent human‐derived target to combat tau pathology.PNY and SSK are co‐first‐authors.RT, WH, and DYK jointly supervised this project.
Application of the modified qualitative scoring of MMSE pentagon test in the differential diagnosis of lewy body dementia and Alzheimer’s disease
Authors: Lu Lu , Zhu Sirui , Meng Xiaosheng , Wang Jing , Li Dan , Li Fangyu , Lu Yuanyuan , Yu Yueyi 
Published: June 2023

AbstractBackgroundTo explore the value of the modified qualitative scoring of MMSE pentagon test (mQSPT) in the differential diagnosis of Lewy body dementia (DLB) and Alzheimer’s disease (AD).MethodStudy the patients who met the inclusion criteria in the Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2018 to August 2021. The baseline data of gender, age and education, Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA) and Clinical Dementia Assessment Scale (CDR) scores of 61 DLB patients and 71 AD patients were analyzed retrospectively. At the same time, the scores of sub items in the scale that can reflect visualspatial impairment were recorded,: i.e. connection test, cube copy, clock drawing test in MoCA, and pentagon copy test in MMSE. The images in MMSE pentagon copy test of these patients were further scored according to QSPT and mQSPT, and compared between the two groups. Multivariate stepwise logistic regression was used to analyze the differential efficacy of QSPT, mQSPT combined with other clinical psychological evaluation between DLB and AD.ResultThere were significant differences between DLB and AD patients in connection test, cube copy, clock drawing test, pentagon copy test, QSPT, mQSPT and gender, but there were no significant differences in MMSE, MoCA, age and education. The sensitivity of QSPT in differentiating DLB and AD was 71.8%, the specificity was 67.2%, the area under ROC curve was 0.682 (95%CI: 0.584‐0.772), and the cut‐off value was 9.5. The sensitivity of mQSPT in differentiating DLB and AD was 68.9%, the specificity was 84.5%, the area under ROC curve was 0.78 (95%CI: 0.696‐0.862), and the cut‐off value was 8.5. Multivariate stepwise logistic regression showed that while QSPT failed to establish any suitable modeling, mQSPT and cube copy were related to the distinction between the two diseases. Moreover, the efficacy of these two indexes to distinguish AD and DLB: the sensitivity was 70.5%, and the specificity was 84.1% and the area under the ROC curve was 0.817(95%CI: 0.743‐0.891).ConclusionThe mQSPT can be used for the screening tool in differential diagnosis between AD and DLB patients.
Defining advance care planning from the perspective of people with dementia: Focus groups with the European Working Group of People with dementia
Authors: Monnet Fanny , Pivodic Lara , Dupont Charlèss , Diaz Ana , Gove Dianne , Van den Block Lieve 
Published: June 2023

AbstractBackgroundThe European Association for Palliative Care (EAPC) defines advance care planning (ACP) as a process enabling individuals with decisional capacity to define goals and preferences for future medical treatment and care, discuss these with family and health‐care providers, and record and review them if appropriate. There are concerns that this and other definitions may not apply to ACP in the context of dementia. ACP needs for people with dementia differ from those of people with other diseases. Furthermore, current definitions are not informed by input from people with dementia, but rely on professional expert recommendations. We gathered the perspectives of the European Working Group of People with Dementia (EWGPWD) regarding the EAPC ACP definition to explore its applicability in the context of dementia.MethodsWe conducted 3 online focus groups with members of the EWGPWD (n = 12) and their supporters (n = 9). We deconstructed ACP in four topics revolving around the what, why, who, and when of ACP to guide discussions. To analyze the data, we used inductive thematic analysis.ResultsThree key issues were highlighted as important to consider in an ACP definition which would be inclusive for people with dementia. First, participants disagreed with the focus on people with decisional capacity, as they saw loss of capacity as a gradual process that depends on context and should be supported throughout the dementia trajectory. Second, although some noted that family dynamics vary, the essential role of families or trust‐based relationships was found to be under‐addressed, as families were generally considered to have personal knowledge of the person with dementia. Third, participants suggested that ACP is too centered on medical care. It should include broader conversations on what matters to people in the future, social care, and future daily life activities.ConclusionWe identified three points of contention with the EAPC ACP definition corresponding to dementia‐specific issues. The perspectives of the EWGPWD emerging from our focus groups contribute to the understanding of ACP in the context of dementia and highlight the need for a dementia‐inclusive ACP definition focusing on the issues of decisional capacity, family involvement and social aspects of care.