bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dementia care in Taiwan during COVID‐19
Authors: Yoon Grace H , Shyu Yea‐Ing L , Lin Paige 
Published: December 2021

AbstractBackgroundTaiwan has been bolstering dementia care policy with the concern of reaching the ‘super‐aging’ mark by 2025. Taiwan’s success in containing the COVID‐19 pandemic involves focused, timely interventions in preventive measures, including policies targeting people living with dementia and their caregivers. This review presents key dementia policy interventions achieved during the pandemic.MethodA scoping review of published academic, media and grey literature was conducted. We extracted relevant information pertaining to dementia care during the COVID‐19 pandemic and summarized the data in a narrative format.ResultTaiwanese government has implemented a policy in April 2020 that restricted visitations to long‐term care facilities, which continues today. Since the start of the pandemic, one nurse and no individuals with dementia living in long‐term care facilities has been infected. A landmark decision was made in April 2020 to ban penalization of people with dementia for violation of the epidemic prevention regulation (e.g., wearing a mask) if they have documentation of disability. This was possible due to the strong, continued advocacy from the Taiwan Alzheimer’s Disease Association (TADA). TADA provided critical resources to the dementia community by releasing online videos to teach patients how to protect themselves and others during the pandemic, such as mask wearing and handwashing. TADA’s Reference Handbook of Dementia Care Responding to COVID‐19was well‐received by the Health Promotion Administration of the Ministry of Health and Welfare, who forwarded the handbook to all local governments and shared these videos on its national official website. There are government‐sponsored facilities across the districts of Taipei City that encourage people with dementia to participate in local activities during the pandemic.ConclusionIn Taiwan, national public health policies quickly came into place since the beginning of the pandemic to curb the spread of COVID‐19 infection in elderly care settings impacting dementia care. Patient advocacy groups have played an important role in providing resources and support to the dementia community. Taiwan’s recent demonstration of quick policy reactions and public‐private partnerships to protect people with dementia and their caregivers provide an effective dementia care model for future response measures.
Sex and ApoE‐4 interactions on development and severity of psychosis in AD
Authors: Tan Yu Bin , Fornazzari Luis , Dissanayake Andrew S. , Churchill Nathan W , Schweizer Tom A. , Munoz David G. , Fischer Corinne E. 
Published: December 2021

AbstractBackgroundNearly half of all Alzheimer’s Disease (AD) patients experiences psychosis at some point in their disease trajectory. Kim et al. (2017) found a sexual dimorphism in AD psychosis where the ε4 allele may play a larger role in influencing psychosis development in females with Lewy body (LB) pathology.MethodWe investigated the effect of sex and ApoE‐4 status on age, presence and severity of psychotic symptoms on a clinical cohort using data from the National Alzheimer’s Disease Coordinating Centre (Figure 1). The non‐psychotic group (AD‐P) was compared against each of the overlapping diagnostic groups – psychotic (AD+P), delusion (AD+D) and hallucination (AD+H).ResultWe found a significant association between ε4 homozygotes and AD+P (OR = 1.08, p =. 017) and AD+D (OR = 1.09, p = .007). There was also a significant association between ε4 heterozygotes and AD+P (OR = 1.09, p = .004) and AD+D (OR = 1.08, p = .012). In males, the likelihood of having two copies of ε4 was increased in AD+P (OR = 1.10, p = .034) and AD+D (OR = 1.13, p = .006). The likelihood of having one copy of ε4 was also increased in AD+P (OR = 1.10, p = .030) and AD+D (OR = 1.10, p = .028). In females, the likelihood of having one copy of ε4 was increased in AD+H (OR = 1.10, p = .033). Participants who were female and homozygous for ε4 had a predicted increase of 0.388 in the log‐odds of being in a more severe category for delusions (95% CI: 0.016 ‐ 0.759, p = .041) and hallucinations (95% CI: 0.011 ‐ 1.264, p = .046).ConclusionOur findings show that the presence of ApoE‐4 increases the risk of psychosis in clinically diagnosed AD patients. Moreover, there are differential associations between sex, ApoE‐4 status and psychotic manifestations. The fact that we did not find an increase risk of psychosis among female homozygous ApoE‐4 carriers may be explained by the fact that we did not stratify by Lewy body pathology (Tsuang et al., 2005).
Impact of mild behavioral impairment on longitudinal changes in cognitive performance
Authors: Rouse Hillary J , Small Brent J , Ismail Zahinoor 
Published: December 2021

AbstractBackgroundRecent research has developed a better appreciation for non‐cognitive factors, such as neuropsychiatric symptoms (NPS), as early indicators for dementia. This has led to the development of criteria for mild behavioral impairment (MBI), or the late‐life onset of NPS. MBI has been associated with a unique cognitive phenotype, but research on longitudinal changes is limited. The goal of this study is to examine if MBI influences changes in cognitive abilities among older adults who are cognitively healthy (CH) or have mild cognitive impairment (MCI).MethodSecondary data analysis of participants (n=17,291) from the National Alzheimer’s Coordinating Center who were CH (n=11,771) or diagnosed with MCI (n=5,520). Almost 25% of the sample met the operationalized diagnostic criteria for MBI (n=4,274). Cognitive performance was evaluated using tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed.ResultsCross‐sectionally, persons with MBI performed worse on tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed compared to people without MBI. There were no significant interactions present between MBI and MCI on any of the tasks. Longitudinally up to 14 years, persons with MBI saw a greater decline on tasks of attention, executive function, language, episodic memory, and processing speed compared to individuals without MBI. Further, older adults with MBI performed significantly worse across time on tasks of executive function, language, and processing speed when compared to CH older adults without MBI. Persons with MBI and MCI performed significantly worse across time on tasks of executive function, language, processing speed, and visuospatial ability when compared to those with only MCI.ConclusionOlder adults with MBI performed worse on all cognitive domains, compared to those without MBI. Additionally, CH older adults with MBI saw a greater decline across time in the domains of executive function, language, and processing speed. In the MCI group, MBI was associated with a greater decline in all of these domains in addition to visuospatial ability. The results provide support for unique cognitive phenotypes for MBI in CH older adults and MCI, that may be indicative of preclinical and prodromal symptoms of dementia.
Cognitive intraindividual variability as a biomarker for functional declines in the Texas Alzheimer’s Research and Care Consortium (TARCC) Longitudinal Hispanic Cohort
Authors: Scott Bonnie M. , Royall Donald R. , Hilsabeck Robin C. 
Published: December 2021

AbstractBackgroundWhile intraindividual variability (IIV) in cognitive performance has been associated with increased risk for cognitive decline, the relative predictive utility of IIV‐across versus IIV‐within different cognitive domains remains unknown. Given that cognitive IIV has also been linked to age‐related reductions in white matter integrity, the current study aimed to determine if IIV‐within a “frontal‐subcortical” domain may be a more robust predictor of functional declines over time than IIV‐across cognitive domains.MethodsParticipants included 651 controls, 211 MCI and 218 AD patients enrolled in the TARCC Hispanic Longitudinal Cohort. Mixed Linear Modeling was used to examine the fixed effects of static predictors (i.e., age, education, gender, ethnicity, APOE genotype, cognitive status) at baseline, and the fixed and random effects of time‐varying covariates (i.e., depression, pulse pressure, IIV‐across domains, and IIV‐within the frontal‐subcortical domain) on changes in functional independence over 5 years.ResultsAge, education and ethnicity moderated the relationship between APOE genotype, baseline cognitive status and declines in functional independence over time. Overall, greater pulse pressure, IIV‐across domains and IIV‐within the frontal‐subcortical domain were all associated with larger decrements in functional independence over time. Although increases in IIV‐across domains were primarily driven by increases in IIV‐within the frontal‐subcortical domain over time, the former emerged as a stronger predictor of functional independence than the latter. Gender and education significantly influenced individual differences in rates of change over time, while the effects of IIV‐across domains and IIV‐within the frontal‐subcortical domain on functional declines differed from person‐to‐person. The addition of cognitive IIV predictors significantly improved model fit with a 1498.3 reduction in ‐2LL (p < 0.001). The final model accounted for 97.8% of the variance in functional independence over time.ConclusionsResults suggest that IIV‐across domains may be a robust biomarker of subsequent declines in functional independence and changes in this metric are primarily driven by increasing variability across tasks dependent on frontal‐subcortical circuitry. Findings also highlight important considerations for the development of future clinical trials aimed at early prevention and treatment, including the significance of demographic and clinical characteristics in moderating the risk of decline in functional independence over time.
A data‐driven examination of clustering of apathy and depression symptoms in people with dementia
Authors: Da Silva Miguel Vasconcelos , Melendez‐Torres G.J. , Testad Ingelin , Ballard Clive , Creese Byron 
Published: December 2021

AbstractBackgroundApathy is one of the most common Neuropsychiatric Symptom (NPS) and is associated with poor clinical outcomes. Apathy remains under‐researched and its medical classification remains unclear, potentially associated with the fact that apathy is commonly a comorbidity with depression. Research that helps define the apathy phenotype is urgently needed, particularly for clinical and biomarker studies.MethodUsing latent class analysis (LCA) we analysed data from the KCL Care Home Research Network study with 349 participants (an observational study of people living with dementia in care homes). The aim was to understand how apathy and depression phenotypes cluster together. Apathy and depression were defined on the basis of item G (Apathy) and D (Depression) of the NPI‐NH scale, combining the 7 apathy subquestions with the 8 depression subquestions, rated as yes or no. Predictors of class membership were then analysed, including other NPS, demographics, medication and Clinical Dementia Rating (CDR).ResultThe LCA analysis showed a 4‐cluster group which was considered the best model: No symptoms, predominantly depression, apathy/depression, and a predominantly apathy group. Those in the apathy/depression class were more likely to experience psychosis symptoms compared to the no symptoms class, whilst those in the predominantly apathy class were more likely to have a higher CDR score compared to the no symptoms class.ConclusionUsing a data driven method, we show distinct clustering of apathy and depression symptoms in this cohort. There was evidence that these clusters have different clinical associations which may help inform diagnostic categories for research studies and clinical practice. Potentially, the four subtypes may be used in future studies to further evaluate their utility in biomarker studies in dementia.
Using a virtual reality path integration task to investigate entorhinal functioning in individuals with and without subjective cognitive decline
Authors: Alkan Merve , Bierbrauer Anne , Kunz Lukas , Axmacher Nikolai , Jessen Frank 
Published: December 2021

AbstractBackgroundThe entorhinal cortex (EC) contains spatially modulated cells, so called grid cells, and plays a central role in spatial navigation. Studies show that tauopathy in the EC is already observed in the early stages of Alzheimer's disease (AD) and is responsible for impairments in spatial memory performance. Moreover, recent studies demonstrate that young, healthy volunteers with the APOE‐ε4‐allele, a genetic risk factor for AD, show impaired grid‐like representations in the EC and reduced path integration performance in environments without spatial cues. People with subjective cognitive decline (SCD) perceive a subjective deterioration in their cognitive memory performance with unimpaired performance on standardized neuropsychological tests. SCD corresponds to the recently defined stage 2 of AD and is also a risk factor for dementia. Here, we tested whether subjects with SCD show path integration impairment, presumably related to malfunctioning in the EC.Method68 participants (31 SCD patients recruited through a memory clinic, age: 68.8 ± 9.2; 37 controls without SCD, age: 69.1 ± 7.9) performed a path integration task on a laptop. In addition, a neuropsychological test (CERAD+) was carried out to rule out an objective cognitive impairment.ResultThe two groups did not differ in age, sex, medical history and number of educational years. We replicated previous findings indicating better path integration performance with spatial cues such as boundaries and landmarks (F(2,128) = 20.83, P < 0.001). In addition, we showed that women performed worse than men (F(1,64) = 6.00, P = 0.017) and that path integration performance declined with increasing age (F(1,64) = 32.14, P < 0.001). There was no significant difference in performance between SCD and controls (F(1,64) = 2.20, P = 0.143).ConclusionGenerally, SCD was not associated with lower path integration performance. We are in the process of characterizing the sample based on plasma amyloid beta 42/40, NFL, pTau and APOE genotype to test, if AD biomarkers and genetic risk factors are associated with path integration performance.
The Amsterdam Experience: Insights from 7 years of retinal biomarker experience in a tertiary memory clinic
Authors: den Haan Jurre 
Published: December 2021

AbstractBackgroundThe retina, embryologically derived from the neural tube, contains neurons, glial cells and vasculature similar to the brain and as an extension of the central nervous system may provide patient friendly, inexpensive and disease specific biomarkers that could aid diagnosis for the clinician in current clinical practice and serve as therapeutic read‐out in clinical trials.MethodsOver the last 7 years research in the Amsterdam Dementia Cohort using in‐vivo methods in the form of optical coherence tomography (OCT), fundus photography, OCT angiography and fluorescence imaging and ex‐vivo methods were used for biomarker discovery. These studies aimed to identify biomarkers for amyloid (A), tau (T), neurodegeneration (N) and vasculature (V).Result and ConclusionHere we present an overview of the data collected together with the valuable lessons learned from the specific projects. Caveats of the current methods and suggestions for future research will be presented to move the field of retinal biomarker discovery and validation further.
The shift to virtual, Part 1: Adoption of virtual options by older populations for clinical care, health education resources, and social interaction
Authors: Lock Sarah Lenz 
Published: December 2021

AbstractBackgroundThe pandemic has created new barriers for the delivery of healthcare resources and information, as well as in‐person delivery of health care, caregiving and social engagement. This is particularly true for people in nursing facilities, particularly those with dementia often resulting in tragic consequences. Social distancing, masks and lock downs along with lack and shortages of PPE prevented the physical presence and contact of people engaged in delivering dementia care causing greater suffering of people living with dementia, and enormous stress to providers, family and friends. This has necessitated a major shift in how people access both human interaction and healthcare information. This presentation will provide lessons learned from the transition to virtual‐based public education and virtual social interaction aimed at mitigating the risk of exposure to COVID‐19 and harms of social isolation.MethodThis dramatic shift has necessitated a explosive adoption of telemedicine and alternative, technological visitation as well as a more targeted approach to virtual public health campaigns focused on older adults. A natural experiment has been created as we rushed to adopt virtual communication methods to deliver vital services for older people, including those with cognitive impairment.ResultEfforts will be made to track the results and long‐term implications for adoption of telehealth resources and virtual visitation for older populations concerned about cognitive health as well as those living with dementia and their caregivers.ConclusionPublic policies are being developed to assist in the adoption and use of technology for delivery of health care information, telemedicine, visitation to combat social isolation. The lessons learned should inform the future of long term care policies for people with dementia and their caregivers.
An examination of atypical primary progressive aphasia variants
Authors: Botha Hugo , Duffy Joseph R , Utianski Rene L , Machulda Mary M. , Clark Heather M , Strand Edythe A , Boland Sarah , Ali Farwa , Martin Peter R , Buciuc Marina , Boeve Bradley F. , Schwarz Christopher G. , Senjem Matthew L. , Reid Robert I. , Jones David T. , Graff‐Radford Jonathan , Knopman David S. , Petersen Ronald C. , Bigio Eileen H , Lowe Val J , Reichard Ross R. , Jack Clifford R. , Ertekin‐Taner Nilufer , Rademakers Rosa , DeTure Michael , Ross Owen A. , Dickson Dennis W , Whitwell Jennifer L , Josephs Keith A 
Published: December 2021

AbstractBackgroundThe Neurodegenerative Research Group (NRG) at Mayo clinic has followed patients with degenerative speech and/or language disorders for over a decade. In this presentation I will present data from this cohort to inform a broader discussion about the importance of apraxia of speech (AOS) and its subtypes, heterogeneity within the agrammatic PPA variant, and perils of mixed phenotypes.MethodWe reviewed the NRG database to identify patients who initially presented with isolated (PPAOS), AOS in conjunction with agrammatic aphasia (AOS‐PAA), isolated agrammatic aphasia (PAA), and patients who had PAA or AOS overlapping with another degenerative diagnosis. Data from the following clinical instruments were abstracted: WAB AQ (aphasia severity), UPDRS III (parkinsonism), WAB Praxis (ideomotor apraxia), and the MoCA (cognitive ability). We assessed the effect of baseline diagnosis and AOS subtype on these outcomes over time using Bayesian linear mixed effects models. We qualitatively reviewed longitudinal diagnostic trajectories. Preliminary analyses were done on available autopsy data.ResultPAA was associated with greater aphasia at baseline and more rapid decline; PPAOS was associated with normal language at baseline and slow decline; and PAA‐AOS with intermediate baseline aphasia and decline. However, for those with AOS longitudinal decline differed based on AOS subtype: prosodic PPAOS was associated with the slowest decline and phonetic PAA‐AOS with the fastest. Some patients met criteria for non‐PPA disorders during follow up. However, compared to patients who met criteria for these disorders at enrollment, the speech/language‐first patients remained qualitatively distinct, and neither resembled the cases that were mixed at onset. Preliminary autopsy data suggests that AOS is predictive of tau and that the specific tauopathy may be related to the initial syndrome and AOS subtype.ConclusionThe differences between PAA, PAA‐AOS and PPAOS suggest that these disorders should not be lumped. In fact, the longitudinal trajectories are sufficiently different that doing so would add noise to observational and interventional studies. Instead, more detailed phenotyping, including AOS subtype, can aid prognostication and may improve prediction of the underlying pathology. Finally, caution should be exercised when considering PPAOS and PPA patients for other FTLD diagnostic categories.
A data‐driven latent atrophy factor model reveals differential associations between relative frontal atrophy patterns and specific neuropsychiatric symptoms in Alzheimer’s disease
Authors: Singleton Ellen H. , Groot Colin , Bader Ilse , Papma Janne M. , Scheltens Philip , Pijnenburg Yolande A.L. , Ossenkoppele Rik 
Published: December 2021

AbstractBackgroundto examine the relative role of the frontal cortex in neuropsychiatric symptoms in Alzheimer’s disease (AD), we assessed associations between latent atrophy factors and neuropsychiatric symptoms in AD.MethodWe employed a data‐driven Bayesian modelling framework based on Latent Dirichlet Allocation (LDA) to identify latent atrophy factors in a cohort of 1135 Aβ‐positive MCI and AD patients from the Amsterdam Dementia Cohort (age: 66.4±7.44, 50% male, MMSE: 22.3±0.1). The model uses standardized gray matter density images as input, adjusted for age, sex, intracranial volume and scanner field strength, and yields voxelwise probabilistic maps for a predetermined number of atrophy factors, providing data–driven factor expression loadings per individual. These factor expressions were correlated to scores on the Neuropsychiatric Inventory (NPI) using general linear models, adjusting for sex, age, education and MMSE scores.Resultthe LDA model revealed a frontal (dorsolateral and insular), a medial temporal lobe (hippocampal and entorhinal), a temporoparietal and a late‐stage (sensorimotor and occipital) factor (Figure 1). The highest percentage of individual expressions was found in the late‐stage factor (34.0±0.6), followed by the MTL (27.3±0.6), TPC (22.0±0.5) and frontal (16.7±0.5) factors (Figure 2). Higher frontal expression relative to both the MTL and late‐stage factors was associated with a higher odds for apathy (MTL; OR=1.012, p=0.010, late‐stage; OR=1.011, p=0.046; Figure 3). Negative associations, however, were found between relative frontal atrophy and disinhibition, anxiety and nighttime behaviors (Figure 3); a higher frontal load relative to each reference factor related to a lower odds for disinhibition (frontal‐MTL: OR=0.978, p=0.035; frontal‐TPC: OR=0.969, p=0.042; frontal‐‘late‐stage’: OR=0.976, p=0.029), a higher frontal load relative to MTL and late‐stage factors were associated with a lower odd for anxiety (frontal‐MTL: OR=0.984, p=0.015; frontal‐‘late‐stage’: OR=0.983, p=0.003) and night‐time behaviors (frontal‐MTL: OR=0.982, p=0.023; frontal‐‘late‐stage’: OR=0.980, p=0.005).ConclusionRelative frontal atrophy was related to more frequent apathy and less frequent disinhibition, anxiety and night‐time behaviors and may point towards more AD‐typical regions as determining neurobiological regions for disinhibition, anxiety and night‐time behaviors than frontal regions in AD. Alternatively, disinhibition may be more dependent on the right frontal pole, less prominently involved in the current frontal factor.