bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter hyperintensities and mild behavioural impairment: Findings from the MEMENTO Study
Authors: Miao Ruxin , Chen Hung‐Yu , Robert Philippe , Smith Eric E. , Ismail Zahinoor 
Published: December 2021

AbstractBackgroundMild behavioural impairment (MBI) is a neurobehavioural syndrome characterized by the onset and persistence of neuropsychiatric symptoms (NPS) in later life. While the ATN framework provides a robust overview of Alzheimer’s pathology, it does not fully capture the impact of small‐vessel cerebrovascular disease in the pathogenesis of dementia. White matter hyperintensities (WMH) may independently contribute to the development of Alzheimer’s dementia and predict risk of incident dementia in mild cognitive impairment (MCI). Few studies have established the link between NPS and WMH in MCI populations.MethodWe included 760 participants from the French MEMENTO study with MCI and WMH data. WMH volumetry on T2‐weighted fluid attenuated inversion recovery images was identified using WHASA software, visually verified with the Fazekas and Schmidt scale, and expressed in cm3. Mean age was 72.7 (SD 8.0) and 57.9% of participants were female. Neuropsychiatric Inventory items were transformed to MBI domains using a published algorithm. MBI status was based on symptom persistence: NPS at both baseline and 6‐months was considered MBI+ (n = 227), whereas non‐persistent NPS (i.e., NPS at either time point but not both) or no NPS at either baseline or 6‐months was considered MBI‐ (n=549). We investigated the association between MBI status and the outcome variable, WMH, using a linear regression model adjusted for age, sex, education, Mini‐Mental Status Exam (MMSE) score, and total intracranial volume.ResultMBI was present in 29.9% of participants (n = 227). MBI+ (i.e., persistent NPS) was significantly associated with lower MMSE score (p < 0.001) and male sex (p = 0.025). Compared to MBI‐, MBI+ was associated with 9.9% higher WMH volume [p = 0.006 (95% CI 2.8% to 18%), Table 1].ConclusionIn a memory clinic sample of older adults with MCI, MBI+, operationalized as persistent NPS, is associated with higher WMH. These findings extend the evidence base linking MBI with known dementia biomarkers and raise the possibility that some forms of MBI can be caused by vascular brain injury.
Outreach Pro: The National Institute on Aging’s (NIA) online tool for AD/ADRD clinical studies recruitment and engagement of diverse and underserved populations
Authors: Massett Holly A , McGowan Melissa , Gallop‐Goodman Gerda 
Published: December 2021

AbstractBackgroundNIA aims to increase awareness and interest in Alzheimer’s and related dementias (AD/ADRD) research among non‐White populations. Easily accessible, well‐tested, culturally appropriate outreach materials addressing AD/ADRD and clinical research is an identified need by researchers to better reach communities of color. To address this gap, NIA has both invested substantial resources to create materials for African Americans (AA), Hispanics/Latinos (H/L) and Asian Americans/Pacific Islanders (AAPI), and developed a new online platform, Outreach Pro, where researchers/stakeholders can tailor and brand communication campaigns locally.MethodOutreach Pro and its content were created iteratively using a mixed‐method approach: literature reviews, environmental scans, stakeholder listening groups (N=9), focus groups (N=33), national surveys (N=3), and usability testing (N=20). Materials were developed working with creative designers and researchers representing each cultural group and languages. Final creatives were added into the Outreach Pro and tested with representatives from the AD/ADRD community.ResultOutreach Pro is fully developed and will be formally launched as part of this presentation. The online tool, using a series of pre‐programmed questions, allows users to develop tailored and branded local campaigns selecting from the tool’s library of nationally tested messages, taglines, concepts, and images. User‐testing indicated overall high usability and user‐sentiment towards the site (SUSS=76; NPS=60). Outreach Pro contains materials developed for AA and H/L audiences, including: leave behind brochures/factsheets, online libraries of well‐tested photos/images, videos, social media posts, and motion graphics. H/L materials are available in both Spanish and English. A set of materials for AAPI is currently in development and being tested in three languages.ConclusionOur findings illustrate the importance of both designing well‐tested, culturally appropriate materials and making them easily accessible and customizable to stakeholders on a local level. NIA designed Outreach Pro to reduce redundancies; users of the platform can save and share their customized campaign in a centralized location. NIA plans to evaluate the tool and identify areas where its content can be scaled up to address other aging‐related research.
A 3‐month toxicity study of GB‐5001, a donepezil one‐month depot injection formulation, by intramuscular injection in dogs
Authors: Yoon Kwonhyeok , Choi Jaemook , Seol Eunyoung , Lee Juhan , Choe Heekyoung , Lee Soojung , Lee Heeyong 
Published: December 2021

AbstractBackgroundDonepezil, an acetylcholinesterase inhibitor for treatment of Alzheimer’s disease (AD), is administered as daily tablets. The treatment compliance, however, is particularly challenging in AD patients for various reasons such as difficulty in swallowing medication, tolerating side effects, and/or complying with the appropriate dosage. GB‐5001 is a novel once monthly intramuscular (IM) depot injection of donepezil to improve treatment compliance developed using G2GBIO’s InnoLAMP® technology. The objective of this study was to evaluate the toxicity of GB‐5001 in beagle dogs for further development.MethodGB‐5001 was administered once every 4 weeks via bolus IM injection to 16 male and 16 female beagle dogs (7.4∼13.3 kg) for 3 months, and 4 male dogs and 4 female dogs in the vehicle group and the highest dose level group were evaluated for the reversibility or long‐term effects following a 2‐month non‐dosing recovery period. The dose levels were 0 (vehicle), 280, 560, and 1120 mg/dose. The following parameters and endpoints were evaluated in this study: standard toxicology parameters, ophthalmoscopic, electrocardiographic examination, gross, histopathologic examinations, and toxicokinetic parameters.ResultNo fatality occurred during this study and there were no toxicologically significant clinical changes or pathological findings related to GB‐5001 in all groups. Systemic exposure to Donepezil was independent of sex. Following IM injection once every 4‐weeks of GB‐5001, mean Cmax and AUC0‐last values of Donepezil increased dose dependently on Days 1 and 57. And systemic exposure (AUC0‐last) to Donepezil increased slightly (<2 fold) on Day 57 compared to Day 1.ConclusionGB‐5001 was tolerated at all dose levels when administered once every 4 weeks via IM injection to male and female beagle dogs for 3 months at doses of 0, 280, 560 and 1120 mg/dose. The clinical observations of swelling and nodules at the dose sites are considered to be vehicle‐related as evidenced by the similar incidence in control. Consequently, the no‐observed‐adverse‐effect‐level (NOAEL) is considered to be 1120 mg/dose.
Investigating predictors of incident cognitive impairment in women
Authors: Casanova Ramon , Gaussoin Sarah A , Hayden Kathleen M , Shadyab Aladdin H , Canell Brad , Chen Jiu‐Chiuan , Liu Simin , Chan Kei Hang Katie , Henderson Victor , Craft Suzanne , Rapp Stephen R 
Published: December 2021

AbstractBackgroundMore women than men are affected by Alzheimer’s disease (AD). However, risk factors for cognitive impairment (CI) among older women by race/ethnicity are not completely understood. The well‐characterized Women’s Health Initiative Memory Study (WHIMS) has followed for more than 25 years postmenopausal women to assess cognitive and brain outcomes. WHIMS provides a unique opportunity to determine the extent to which risk factors for CI vary between White and Black women. Due to the high‐dimensional nature of this problem we based our analyses on machine learning methods.MethodTo investigate signatures of predictors of incident CI (either mild cognitive impairment or probable dementia) in women, we included 6778 women (503 Black and 6275 White) with up to 25 years of follow‐up including annual cognitive assessments. Mild cognitive impairment and probable dementia were adjudicated annually across all phases of the trial and subsequent observational study by a central, multidisciplinary adjudication panel of experts. We selected 52 potential predictors collected at baseline representing different domains–demographic, health, social, psycho‐social, biological, and medical. Survival Random Forests (SRF) were used to identify the most reliable predictors of incident CI. Here we use the SRF implementation available in the RandomForestSRC R library. SRF models were fitted independently using White and Black participants based on the default parameters of the software. The permutation index was used to determine predictors’ relevance. The concordance index was used as a measure of model performance.ResultThe most important predictors of incident CI in Black women were lower education, higher systolic blood pressure, lower income and higher high‐density lipoprotein cholesterol. The concordance index was 0.64. A different profile of predictors was observed among White women. Baseline age was the most relevant predictor of ICI followed by self‐reported forgetfulness, self‐reported difficulty concentrating, physical function and higher depression. The concordance index for this model was 0.71.ConclusionPhenotypic signatures predicting incident CI differed between older Black and White women. Education, markers of vascular disease and income were major predictors in Black women and age, self‐reported cognitive difficulties, physical function and mood were major predictors in White women.
The crosstalk between beta‐amyloid, retina, and sleep for the early diagnosis of Alzheimer’s disease: A mini review
Authors: De Guia Isaiah‐Lorenzo , Gupta Sunil M. , Naismith Sharon L. , Chatterjee Pratishtha , Dias Cintia B. , Fuller Stephanie , Shah Tejal M. , Martins Ralph N. 
Published: December 2021

AbstractBackgroundRetinal imaging has the potential to be used as an early diagnostic tool in Alzheimer’s disease (AD). However, direct visualisation of AD related hallmark proteins in the live human retina is challenging and may require the inclusion of additional factors to be effective. This mini review gathers evidence to understand the associations and underlying mechanisms between beta‐amyloid (Aβ, a hallmark feature found in the AD brain), the retina and sleep as collectively they would enhance the diagnostic accuracy of the retinal markers in AD.MethodRetinal imaging has the potential to be used as an early diagnostic tool in Alzheimer’s disease (AD). However, direct visualisation of AD related hallmark proteins in the live human retina is challenging and may require the inclusion of additional factors to be effective. This mini review gathers evidence to understand the associations and underlying mechanisms between beta‐amyloid (Aβ, a hallmark feature found in the AD brain), the retina and sleep as collectively they would enhance the diagnostic accuracy of the retinal markers in AD.ResultRetinal imaging has the potential to be used as an early diagnostic tool in Alzheimer’s disease (AD). However, direct visualisation of AD related hallmark proteins in the live human retina is challenging and may require the inclusion of additional factors to be effective. This mini review gathers evidence to understand the associations and underlying mechanisms between beta‐amyloid (Aβ, a hallmark feature found in the AD brain), the retina and sleep as collectively they would enhance the diagnostic accuracy of the retinal markers in AD.ConclusionThere is mounting evidence that the coupling of chronobiological information such as circadian rhythm dysfunction and sleep deficiency to retinal biomarker changes will increase the potential utility of retinal imaging in early AD diagnosis.
Amyloid‐tau‐neurodegeneration (ATN) profiles and influence of age‐of‐onset on cognitive trajectories in a Southeast Asian cohort: SYNC project
Authors: Vipin Ashwati , Koh Chen Ling , Wong Benjamin , Zailan Fatin Zahra , Tan Yi Jayne , Soo See Ann , Satish Vaynii , Kumar Dilip , Wang Brian Zhiyang , Ng Adeline Su Lyn , Chiew Hui Jin , Ng Kok Pin , Kandiah Nagaendran 
Published: December 2021

AbstractBackgroundThe amyloid‐tau‐neurodegeneration (ATN) scheme enables unbiased biomarker‐based diagnoses, independent of cognitive status and temporal ordering of AD pathogenic mechanisms [Jack et al.,2016]. ATN profiles in the diverse Southeast‐Asian region will provide important insights into the ATN framework and its association with cognition [Hilal et al.,2017; Knopman et al., 2018]. We examined the effect of amyloid‐beta status on longitudinal cognitive trajectory in young and late‐onset patients as well as impact of ATN categories on longitudinal cognition in a Southeast‐Asian cohort. We hypothesized that age of onset would differentially influence the association between amyloid status and longitudinal cognition.MethodWe studied 92 patients with cognitive impairment from the Singapore YouNg Dementia Cohort. Patients underwent structural‐MRI and lumbar puncture for cerebrospinal fluid amyloid‐beta (1–42), phosphorylated‐tau (p‐tau) and total‐tau (t‐tau) to assess biomarker positivity [Blennow et al., 2020]. A cut‐off age of 60 years was used to define young‐onset cognitive impairment. Separately, ATN profiles were assigned based on cerebrospinal fluid biomarker levels: normal biomarker profile (A‐T‐N‐), suspected non‐Alzheimer’s pathology (SNAP: A‐T±N±) and Alzheimer’s continuum (A+T±N±). Linear mixed effects models assessed longitudinal group differences in mini‐mental state examination (MMSE) trajectory.ResultYoung (<60yrs) sporadic amyloid‐positive, patients demonstrated significantly greater decline in longitudinal MMSE scores (AmyloidStatus*AgeOfOnset*Time: β=2.82, p=0.0193; Fig. 1) compared to older (≥60yrs) amyloid‐positive counterparts. Across the three ATN categories, there were no differences in baseline age, sex, white matter hyperintensities, medial temporal atrophy or APOE4 status (Table 1). Patients along the Alzheimer’s continuum showed a greater decline in MMSE scores over time compared to both normal biomarker A‐T‐N‐ (β=−2.23, p=0.001; Fig. 2‐3) and SNAP patients (β=−2.05, p=0.004; Fig. 2‐3). MMSE decline did not differ between SNAP and A‐T‐N‐ groups.ConclusionWe show steeper MMSE decline in young amyloid‐positive patients than their amyloid‐positive older counterparts. Additionally, Alzheimer’s continuum patients showed steeper MMSE decline than A‐T‐N‐ and SNAP patients. These findings provide insights into mechanisms for the more aggressive cognitive decline frequently observed in younger patients.
The amnestic syndrome of hippocampal type is frequent in patients without hippocampal atrophy in a memory clinic population
Authors: Beaulieu Emilie , Perrier‐Ferland Louis‐Charles , Langlois Francis , Bocti Christian 
Published: December 2021

AbstractBackgroundSince 2011, diagnostic criteria for Alzheimer’s Disease have led to the introduction of biomarkers. Hippocampal atrophy, either volumetric or visually‐rated is arguably the most widely available biomarker of neurodegeneration. An association with a specific type of amnestic disorder has been claimed, but the clinical validity of this concept remains to be established in unselected patient populations. This problem is important as the amnestic syndrome of the hippocampal type is theoretically a key element in the diagnosis of the most common clinical syndrome of Alzheimer’s disease. Our objective was to determine the correlation between the amnestic syndrome of hippocampal type and hippocampal atrophy.MethodThis is a retrospective study of 274 consecutive patients who were assessed in the Memory Clinic between 01/2014 and 11/2018. Verbal memory was assessed with the Free and Cued Selective Reminding Test (FCSRT) and the Montreal Cognitive Assessment Memory Index Score. Brain imaging was performed within six months of the neuropsycholgical assessment and hippocampal atrophy was estimated using the Scheltens Scale, adjusted for age.ResultThe Scheltens scale had a moderate correlation with FCSRT free recall (Pearson correlation = ‐0,425, p<0,001) and weak correlation with FCSRT Cueing index (Pearson correlation = ‐ 0,293, p< 0,001). However, 34% of our cohort (n=93) had an abnormal FCSRT Cueing index (< = 71%), but a normal Scheltens score. As for the MoCA‐MIS, 26% of our cohort (n=57) had an abnormal score (< = 7), but a normal Scheltens score.ConclusionA large subgroup of our patients demonstrate an amnestic syndrome of the hippocampal type, without showing hippocampal atrophy on routine brain imaging. Our results show the limits of equating hippocampal atrophy with the particular profile of amnesia that does not improve with cueing. The claimed specificity of this type of cognitive deficit in the differential diagnosis of dementia needs to be re‐assessed.
Conversational artificial intelligence and affective social robot for monitoring health and well‐being of people with dementia
Authors: Wairagkar Maitreyee , De Lima Maria Raposo , Harrison Matthew , Batey Philippa , Daniels Sarah , Barnaghi Payam , Sharp David J , Vaidyanathan Ravi 
Published: December 2021

AbstractBackgroundSocial robots are anthropomorphised platforms developed to interact with humans, using natural language, offering an accessible and intuitive interface suited to diverse cognitive abilities. Social robots can be used to support people with dementia (PwD) and carers in their homes managing medication, hydration, appointments, and evaluating mood, wellbeing, and potentially cognitive decline. Such robots have potential to reduce care burden and prolong independent living, yet translation into PwD use remains insignificant.MethodWe have developed two social robots ‐ a conversational robot and a digital social robot for mobile devices capable of communicating through natural language (powered by Amazon Alexa) and facial expressions that ask PwD daily questions about their health and wellbeing and also provide digital assistant functionality. We record data comprising of PwD’s responses to daily questions, audio speech and text of conversations with Alexa to automatically monitor their health and wellbeing using machine learning. We followed user‐centric development processes by conducting focus groups with 13 carers, 2 PwD and 5 clinicians to iterate the design. We are testing social robot with 3 PwD in their homes for ten weeks.ResultWe received positive feedback on social robot from focus group participants. Ease of use, low maintenance, accessibility, assistance with medication, supporting with health and wellbeing were identified as the key opportunities for social robots. Based on responses to a daily questionnaire, our robots generate a report detailing PwD wellbeing that is automatically sent via email to family members or carers. This information is also stored systematically in a database that can help clinicians monitor their patients remotely. We use natural language processing to analyse conversations and identify topics of interest to PwD such that robot behaviour could be adapted. We process speech using signal processing and machine learning classifiers to identify emotions and mood.ConclusionAffective social robots with voice and facial expressions have a great potential for enhancing dementia care at home. Combining responses to daily questions, topics of conversations and emotions from speech analysis can help assess daily status of PwD automatically and monitor their health and well‐being over time remotely.
A Month in Neurodegenerative Disease Research (AMiNDR): The evolution of an open‐access podcast series for Alzheimer's researchers
Authors: Rowe Elyn M , Louadi Sarah , Koch Ellen , Kuhlmann Naila , Kamesh Anusha 
Published: December 2021

AbstractBackgroundWith the increasing strain on researchers’ time and the constant flow of new publications, staying up to date with the latest findings in the field of Alzheimer’s disease research is more challenging than ever. To address this problem, we launched a podcast series in June 2020 which covers primary peer‐reviewed articles. Each episode comes with a bibliography citing the abstracts covered, and a description by theme. Since then, we have focused on program evaluation and quality improvement with the following aims: 1) Implement a systematic and consistent approach within the team and across episodes, 2) Increase our global reach, and 3) Provide a valuable service to researchers.MethodsAreas for improvement were identified by the core founders of the podcast, 25 new team members, and listener feedback. 1) A systematic approach to sorting papers into defined themes was developed based on thematic coding of abstracts to identify major themes and sub‐themes. We also implemented quality control measures and standardized hosting procedures. 2) To evaluate our reach, we used analytics from the Simplecast podcast platform to track the number of downloads over time and the geographical location of our listeners. 3) Formal and informal feedback was collected through a survey and social media platforms, respectively. We also plan to assess additional analytics to track the use of our bibliographies to evaluate their value and whether our podcast prompted listeners to consult the original article.ResultsFrom our original four broad‐strokes themes in early 2020, we have expanded to 25 themes to curate focused episodes on topics relevant to researchers. We also developed a semi‐automated quality control regimen to ensure that we cover all papers that appear on PubMed each month, without duplicates. To standardize summarizing and hosting procedures, we created guidelines to train new members of our team. We have received significantly more positive feedback for our recent series that implemented the improvements, and observed a gradual increase in our weekly downloads from a global listener base.ConclusionWith the feedback received and data collected on listener trends, it seems that researchers worldwide are benefiting from our podcast platform and its improvements.