bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau conformational changes in aging‐related tau astrogliopathy.
Authors: Rodriguez Roberta Diehl , Grinberg Lea T. , Suemoto Claudia Kimie , Socher Karen L R , Ferretti‐Rebustini Renata Eloah de Lucena , Leite Renata Elaine Paraizo , Jacob‐Filho Wilson , Pasquallucci Carlos Augusto , Nitrini Ricardo 
Published: December 2023

AbstractBackgroundThe presence of aging‐related tau astrogliopathy (ARTAG) is highly frequent, but poorly characterized in aging brain and neurodegeneration. Over the abnormal tau accumulation processes, tau protein undergoes pathological modifications and the sequency of these pathological events can be associated with different levels of tau aggregation.MethodTo evaluate the frequency of ARTAG in a large population‐based study, we analyzed brain sections immunostained with phosphor tau (AT8) of 1151 individuals with previous neuropathological evaluation. Further, to investigate early stages of tau protein aggregation in ARTAG, we performed additional immunohistochemistry in the amygdala of 32 cases with ARTAG pathology using the following tau antibodies: AT100 and Tau‐C3.ResultARTAG was frequently observed in cognitively normal individuals independent of concomitant neurodegenerative disease. Higher burden of Alzheimer‐type pathology was observed in ARTAG compared to non‐ARTAG. Also, presence of more than one pathology (mixed pathology) was higher in ARTAG compared to non‐ARTAG (p<0.001). Additionally, AT100 immunoreactive ARTAG was found in overall cases, while Tau‐C3 immunoreactive ARTAG was not observed in 12 cases (36%), showing different mature stage for ARTAG compared to neurofibrillary tangles.ConclusionDifferent immunological markers can be found in ARTAG and Alzheimer’s neurofibrillary pathology in early stages of tau pathological processing, suggesting different levels of abnormal tau aggregates among cases with ARTAG pathology.
Mapping changes in synaptic vesicle protein 2A (SV2A) in neurodegenerative diseases
Authors: Bavarsad Mahsa Shanaki , Spina Salvatore , Seeley William W. , Rabinovici Gil D. , Grinberg Lea T. 
Published: December 2023

AbstractBackgroundSynaptic loss is an early feature of neurodegenerative diseases and the best correlate of clinical decline. Synaptophysin is a pre‐synaptic protein used as a marker of synaptic integrity. Although no biomarker is available to measure synaptic integrity in the clinical setting, various potential PET‐scan tracers are under development. Tracers to detect synaptic vesicle protein 2A (SV2A), an integral glycoprotein in the membrane of synaptic vesicles, are among the most promising among those in development. However, the topographical distribution of SV2A in the human brain and the degree of regional changes in different neurodegenerative conditions are unclear, making it challenging to establish the utility of SV2A tracers in clinical practice. To close this gap, we mapped the density of SV2A in five areas vulnerable to age‐related neuropathology in postmortem brain tissue of subjects with four different types of neurodegenerative disease and healthy controls. Furthermore, we compared SV2A maps to synaptophysin maps obtained from adjacent slides.MethodTable 1 details the subjects' features. The regions of interest include middle and inferior frontal gyri, inferior temporal gyrus, angular gyrus, and CA1 sector/entorhinal cortex. 8 µm thick FFPE adjacent slides underwent immunohistochemistry for SV2A (1:150, Atlas Antibodies, rabbit polyclonal) or synaptophysin (1:75, Atlas Antibodies, rabbit polyclonal). All slides were scanned using a calibrated Zeiss Axioscan and quantified using the Zen software. Density was measured in 40 cortical ROIs (20 white & 20 gray matter) per area/case, randomly distributed. Values were normalized for white matter intensity.ResultSVA2 loss was present in all disease conditions. The pattern of change was region and disease‐specific (Fig 1). Interestingly, the correlation between SV2A and synaptophysin density was poor to moderate (Fig 2).ConclusionReduced SV2A expression/level in all diseases indicates that SV2A is a potential marker to detect neurodegeneration. However, the lack of correlation between synaptophysin and SV2A level changes suggests that these markers signal different pathways. Additional research is needed to investigate the relationship between regional loss of SV2A and its potential significance as a marker for neurodegenerative disorders. We are performing Western blotting and autoradiography in the same samples to confirm the immunohistochemistry findings.
White matter hyperintensity burden does not differentiate SuperAgers from average cognitive agers
Authors: Martersteck Adam , Gutstein Daniel , Sridhar Jaiashre , Zemlock Deborah , Mesulam Marsel , Rogalski Emily J 
Published: December 2023

AbstractBackgroundThe amount of white matter hyperintensity (WMH) found on T2‐weighted imaging has shown a strong relationship with age and is thought to be a marker of ischemia‐associated demyelination or secondary axonal degeneration associated with neurodegenerative disease. Previous healthy older aging studies have shown increased WMH are associated with poorer episodic memory performance and decreased volume of medial temporal lobe regions. Here, we examine if lower WMH are associated with a phenotype of successful cognitive aging, SuperAging. SuperAgers are participants over the age 80 with episodic memory at least as good as that of average middle‐aged adults.MethodWe quantified the WMH volume from T2‐FLAIR imaging with a pre‐trained Bayesian 3D U‐Net convolutional neural network in SuperAgers and cognitively healthy elderly controls (EC) of a similar age and education. All participants underwent the ADNI‐3 FLAIR on the same 3T Prisma MRI. WMH volume was square root transformed to account for the skewed distribution. A 2‐tail independent samples t‐test evaluated the difference in WMH volume between SuperAgers and EC. Additionally, we examined if there were differences within SA and EC groups by sex.Result46 SuperAgers (average age 86.3 ± 1.86; average years of education 16.9 ± 1.9) and 25 EC (average age 87.1 ± 5.17; average years of education 17.1 ± 3.1) met criteria and were included in the study. There was no significant difference in the volume of WMH between SuperAgers and ECs (t = 1.01, p = 0.32). Further, there was no significant difference in WMH by sex within the SuperAging group (t = 0.10, p = 0.92) or EC group (t = 0.82, p = 0.42).ConclusionResistance to the development of WMH, a cross‐sectional marker of cerebrovascular disease and demyelination, does not appear to be a strong discriminating factor in 80+ year‐olds with superior memory function compared to cognitively average agers. Future analyses will include longitudinal changes in WMH and examining regional WMH. Cognitive aging is associated with several underlying brain‐based etiologies, and SuperAging may be better explained by a more sophisticated multi‐modal approach.
Dysphagia Outcomes from a Multidisciplinary Clinic for Persons with Dementia
Authors: Yee Joanne P. , Brates Danielle , Barczi Amelia , Mackowicz‐Torres Meredith , Clark Lindsay R. , Wanninger Ellen , Lewis Brian Lee Young , Kuntz Aaron , Robison Raele Donetha , Gustafson Sara , Kind Amy J. , Rogus‐Pulia Nicole M. 
Published: December 2023

AbstractThe Cognitive Care Clinic (CCC) provides multidisciplinary evaluation for Veterans with dementia and their care partners. Swallowing dysfunction (dysphagia) is estimated to be highly prevalent in this population. However, dysphagia is often considered an end‐stage sequelae of disease progression. Speech‐language pathology (SLP) has been incorporated into the CCC team to facilitate pro‐active dysphagia diagnosis and management. The purpose of this study was to describe the frequency of dysphagia in persons with dementia (PWD) seen in CCC and to determine relationships among patient report of dysphagia and clinical screening results.Multidisciplinary assessments led to consensus diagnosis of dementia subtype. Validated dysphagia screening tools included the Eating Assessment Tool‐10 (EAT‐10), water swallow test (WST), and Test of Masticating and Swallowing Solids (TOMASS). Descriptive statistics were calculated for dementia subtype, stage, and dysphagia measures. Independent samples t‐tests were used to compare the relationship between patient‐reported dysphagia symptoms (mean EAT‐10 scores) with risk for aspiration (WST results).71 Veterans with dementia were evaluated between 2017 and 2022 (mean age = 77, 4% female). The majority had Alzheimer’s disease or mixed etiology (68%) and were in the mild disease stage (52%) using the Functional Assessment Staging Tool. 16 of 58 patients (28%) who completed the EAT‐10 scored 3 or higher indicating risk for dysphagia. 23 of 68 patients (34%) failed the WST. There were no significant differences in EAT‐10 scores between those who passed and failed the WST (mean = 1.4; SD = 3.4 versus mean = 2.8; SD = 2.7). 31 of 63 patients (49%) demonstrated inefficient mastication based on length of total masticatory time on the TOMASS.We found that over half of this predominantly mild‐stage cohort demonstrated clinical signs or reported symptoms of swallowing impairment. This suggests that dysphagia occurs at earlier stages, which is in contrast to typical beliefs about when changes to swallow function present in PWD. Additionally, there were no differences in EAT‐10 scores based on WST outcome and average EAT‐10 scores were low overall, suggesting possible underreporting of dysphagia. Findings from this novel clinic highlight the necessity of incorporating SLPs as part of a dementia care team to provide early identification and management of dysphagia in PWD.
Interference and Facilitation Effects on Stroop‐like Tasks in Older Adults
Authors: Baldo Juliana , Hall Kathleen , Chok Jas M. , Herron Timothy J , Curran Brian , Lwi Sandy J. , Blank Michael , Williams Garrett , Geraci Kristin , Sucich Gabriel , Schendel Krista , Santavicca Isabella , Thomas Lexie , Pebler Peter , Woods David L. 
Published: December 2023

AbstractBackgroundThe effect of aging on susceptibility to interference on Stroop‐like tasks is not clearly understood. Some previous studies have suggested slowed reaction time explains age‐related diminution on Stroop performance, while more recent meta‐analyses suggest that disproportionate interference effects are seen with aging, regardless of slower reaction times. In addition, other variables such as education and IQ have been suggested to mediate Stroop‐like effects in older participants.MethodIn the current study, we assessed the relationship between age and Stroop effects in 348 participants, aged 40‐89, with a wide range of educational achievement. The Stroop tasks were administered as part of a novel computerized neuropsychological battery that utilizes advanced automatic speech recognition and transcription software, the California Cognitive Assessment Battery (CCAB). We are currently utilizing the CCAB to track changes in cognition associated with aging, including evolution of mild cognitive impairment (MCI) and dementia, in an ongoing longitudinal study.ResultMultiple regression analysis showed that age independently predicted both Stroop interference (incongruent minus neutral response times) and facilitation effects (neutral minus congruent response times). However, other variables including gender and vocabulary also independently predicted Stroop facilitation, while gender also independently predicted Stroop interference.ConclusionIn summary, while aging has a significant impact on interference and facilitation effects on Stroop‐like tasks, additional variables such as gender and vocabulary (a proxy for IQ) also play a role in performance on these measures of selective attention.
Plasma biomarkers across the Alzheimer’s disease continuum in the New Zealand‐Dementia Prevention Research Clinics
Authors: Cawston Erin E , Griner Leon , Wong Celestine YE , Myall Daniel , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik , Williams Joanna M , Cutfield Nicholas J , Anderson Tim J , Dalrymple‐Alford John C , Tippett Lynette J ,   The New Zealand‐Dementia Prevention Research Clinics, New Zealand
Published: December 2023

AbstractBackgroundAdvances in ultra‐sensitive immunoassay methods, like Single molecule array (Simoa) technology, show that Alzheimer’s disease (AD) neuropathology can be detected in blood at the earliest stages of AD. This study compared cross‐sectional biomarker profiles for participants from the New Zealand‐Dementia Prevention Research Clinics (NZ‐DPRCs) who spanned the continuum from healthy older adults to a clinical diagnosis of AD.MethodBlood plasma samples were obtained from 253 NZ‐DPRC participants (aged 55 to 87) from their baseline assessment. Participants were classified as cognitively normal adults (CN, n = 34), subjective cognitive decline (SCD, n = 64), non‐amnestic mild cognitive impairment (single and multi‐domain, non‐aMCI, n = 23), amnestic MCI (single and multi‐domain, aMCI, n = 105), and AD (n = 27). Six plasma biomarkers were selected for quantification by the HD‐X Simoa analyser (Quanterix, Billerica, MA; University of Gothenburg, Sweden): AD biomarkers amyloid‐beta peptides (Aß1‐40; Aß1‐42) and phosphorylated tau species (p‐tau181; p‐tau231); neurofilament light (NfL), for general neuronal damage; and glial fibrillary acidic protein (GFAP), for astrocyte activation. Clinical, imaging and genetic demographic data were assessed in relation to the plasma biomarkers.ResultPlasma biomarkers across the five groups (figure 1) were assessed by linear regression adjusted for age and sex. P‐tau181, p‐tau231, GFAP and NfL were natural log‐transformed to approximate normality and improve homogeneity of variance. Biomarkers p‐tau181, p‐tau231, GFAP, NfL, Aß1‐42/Aß1‐40 ratio and Aß1‐42, all showed group effects (P < 0.05; Aß1‐40, p<0.08). Tukey’s HSD post‐hoc test for pairwise group comparisons showed significant differences in GFAP for AD vs CN, SCD, non‐aMCI as well as SCD vs MCI (P < 0.05); p‐tau181 for AD vs CN and SCD (P < 0.05); p‐tau231 for AD vs non‐aMCI (P < 0.05); Aß1‐42 for aMCI vs CN and SCD (P < 0.05); Aß1‐42/Aß1‐40 ratio for SCD vs aMCI (P < 0.05). ROC analysis will be reported for the diagnostic accuracy of these blood analytes.ConclusionSimoa‐quantitated blood biomarkers in the NZ‐DPRC cohort differentiates clinical groups spanning the AD continuum cross‐sectionally.
Correlation between fMRI complexity and cognition in early‐onset Alzheimer’s disease
Authors: Jann Kay , Wang Danny J.J. , Ringman John M 
Published: December 2023

AbstractBackgroundResting state fMRI (rs‐fMRI) studies in Alzheimer’s disease (AD) have shown that the functional connectivity (FC) of resting brain networks is progressively diminished in subjects with mild cognitive impairment (MCI) and AD. However, FC analysis of rs‐fMRI has limited capability to characterize the dynamic fluctuations of rs‐fMRI signals that possess clinically meaningful information. Recently the use of entropy measures as indices of the complexity of rs‐fMRI time‐series that provide alternative and complementary information to current fMRI‐based approaches has been proposed. Unlike FC that relies on the parcellation of nodes or selection of seed regions for network analysis, entropy measures of rs‐fMRI can be calculated on a voxel‐wise basis across the whole brain.MethodHere we investigated the correlation between cognitive performance and rs‐fMRI complexity in a sample of 35 participants (Table1) from the Estudio de Enfermedad de Alzheimer en Jalisciences (EEAJ) project that recruits Latino persons (age 18‐80 yrs) at‐risk for fully‐penetrant ADAD. Imaging data underwent standard preprocessing. Multi‐scale entropy was calculated using Sample Entropy at 6 temporal scales using a pattern matching threshold of m = 2 and sensitivity threshold of r = 0.5. Voxel‐wise partial Spearman‐rank correlation was used to assess the relation between cognitive scores (MoCA, Trails‐B and Reverse Digit Span) including age and gender as covariates.ResultWe found significant positive associations between fMRI complexity and all three cognitive scores across the study cohort. We did not observe any significant negative correlations. The maps for MoCA and Trails‐B show areas in the anterior cingulate cortex (ACC), bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral parietal cortex. Trails‐B additionally revealed areas in the insular cortex and temporal cortex. For Reverse Digit Span the correlation was more widespread and also showed associations in motor and supplementary motor cortex beside dlPFC and parietal cortex.ConclusionAcross three cognitive tests we observed positive correlation with fMRI complexity in areas representing brain networks involved in executive function and memory processes. Impaired cognitive function thus is represented by reduced fMRI complexity. fMRI complexity might provide a novel imaging metric that is indicative of impaired cognitive function and is complementary to existing imaging approaches.
How do people with young onset dementia use technology in the workplace?
Authors: Kokorelias Kristina Marie , Bak Katherine , Nygard Louise , Mäki‐Petäjä‐Leinonon Anna , Nedlund Ann‐Charlotte , Issakainen Mervi , Ryd Charlotta , Boger Jennifer , Astell Arlene J. 
Published: December 2023

AbstractBackgroundPeople who develop young onset dementia while they are working face multiple challenges staying in employment. Technology could provide some support for example, scheduling, tracking, and completing tasks, depending on occupation and environment. This study aimed to learn from the experiences of people with young onset dementia.MethodWe interviewed 28 people with young onset dementia in three countries as part of a larger study into their experiences in the workplace, including the use of technology.ResultThe interviews revealed a number of barriers and facilitators to workplace technology relating to usability, accessibility, and cognitive demands. Technology was used for a variety for tasks and participants shared adaptations they made using everyday technologies to support them in carrying out their jobs.ConclusionThe needs of individuals with young onset dementia for technology in the workplace has so far been under explored in terms of research. Much can be learnt from the workplace experiences of people with young onset dementia to promote development of technological supports alongside other accommodations.
Increasing the influence of the Alzheimer’s research community in shaping the public narrative around AD interventions
Authors: Hendrix Kent , Dickson Samuel P. , Knowlton Newman , Hennessey Sean , Nicodemus‐Johnson Jessie , Hendrix Suzanne B. 
Published: December 2023

AbstractAfter decades of failure in AD drug development, recent approvals signal a shift. The information associated with a new drug approval is scientifically complex and inaccessible to the general public. Historically, clinical researchers publish in scientific journals and rely on clinicians to distribute this information to the public. But with approximately 86%1 of Americans getting news from digital sources, social media has a large influence on public opinion of scientific topics. This influence was seen during the COVID pandemic and with the aducanumab approval. Many of the loudest voices are not scientifically motivated and may have conflicts of interest. It’s important to provide scientific voices.Method: A literature search identified concerns with dissemination of scientific information through social media. Best practices are described for educating the public on scientific topics and building public trust in science. In this context, we evaluate the current transition being experienced in the Alzheimer’s field, and lessons learned over the past several years.Result: Critical issues are: the lack of quality control of results, the tendency to believe the loudest voices, and unreported conflicts of interest. Due to the many failures in the Alzheimer’s field, many are vocal critics all AD data and the tendency is to maintain this negative approach. Many of the social media voices in the Alzheimer’s space have not been involved in AD research and may misrepresent results.Scientist Veerasathpurush Allareddy observed “On social media, scientists have to be clear and succinct, an incentive to eliminate jargon and streamline the message.”3Conclusion: As a field of AD researchers, we have an imperative to help shape the discussion around treatments in Alzheimer’s disease with clear, accurate and usable information. We can also encourage people in our communities to help us spread accurate scientific information as it becomes available to our research community.1. “More than eight‐in‐ten Americans get news from digital devices” https://www.pewresearch.org/fact‐tank/2021/01/12/more‐than‐eight‐in‐ten‐americans‐get‐news‐from‐digital‐devices/2. Huber B, Barnidge M, Gil de Zuniga H, Liu James. “Fostering public trust in science: The role of social media. https://www.researchgate.net/publication/335652963_Fostering_public_trust_in_science_The_role_of_social_mediaSCIENCE “Social media: Good or evil?” 10 Feb 2022 Vol 375, Issue 6581 pp. 608‐609 https://doi.org/10.1126/science.abo2409
Memory Screening in the Community: Increasing access to early detection, diagnosis, and care
Authors: Yang Kao Lee , Kelble Laura M. , Felten Kristen , Carlsson Cynthia M , Clark Lindsay R. 
Published: December 2023

AbstractCommunity‐based memory screening may reduce barriers and increase access to earlier diagnosis and care of Alzheimer’s disease and related dementias (ADRDs). The Memory Screening in the Community program was developed to provide cognitive screens for community members (“customers”) through Aging & Disability Resource Centers (ADRCs) across the state of Wisconsin. We evaluated program results for screens completed between 2/2022‐12/2022.Trained ADRC staff administered a Memory Screening survey to customers during memory screening events, walk‐ins, or scheduled appointments. The Memory Screening survey collected site information, appointment type, demographics, living arrangements, and reasons for screen. Staff administered the Mini‐cog, Animal Naming, and/or AD8 instruments. Upon screen completion, staff indicated whether they recommended customers seek follow‐up evaluation with their primary care providers (PCPs) and provided education. After 6‐9 months, staff followed up with customers who received referrals over telephone to gather post‐screening and outcomes information.647 surveys were completed across 39 counties and 5 tribal communities in Wisconsin (Figure 1). Most (∼52%) evaluations were conducted during a memory screening event and 37.4% of screens were completed due to customer memory concerns. Most customers were White (93.7%), women (70.2%), and between 70‐79 years old (31.7%; see Table). Screen results from 214 customers suggested potential cognitive impairment and they were recommended to follow‐up with their PCPs. Most memory screens included discussions about brain health, potential causes of symptoms, dementia warning signs, and importance of early detection (Figure 2). Of customers who were referred to PCPs and agreed to follow‐up calls (n = 166), 20 have completed follow‐up calls (data collection ongoing). Of these 20, 60% (n = 12) met with their PCPs, and 42% (n = 5) received a dementia diagnosis.The Memory Screening in the Community program is feasible and has potential to provide access for cognitive screening and dementia education, especially among rural communities. In addition, roughly 1/3 of all customers screened were referred to a provider. Preliminary follow‐up data suggests community‐screening programs could facilitate diagnostic evaluation and results will be updated with a larger follow‐up sample. Overall, this evaluation demonstrates that community memory screening programs may be an effective first‐line approach in addressing ADRD‐related concerns in the community.