bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing a protocol for neuroimaging to investigate brain ageing and dementia in collaboration with aboriginal Australian communities
Authors: Lavrencic Louise , Broe Gerald A. , Daylight Gail , Delbaere Kim , Draper Brian , Duma Stephen , Fulham Michael , Hill Thi Yen , Lasschuit Danielle , Piguet Olivier , Poulos Lauren , Rae Caroline , Timbery Alison , Radford Kylie 
Published: February 2022

AbstractBackgroundDementia rates in Aboriginal Australians are 3‐5 times higher than in the broader Australian population, and among the highest rates reported globally. Existing evidence suggests that dementia types are similar to those found in non‐Indigenous Australian populations. Neuroimaging, however, has not been previously available in any study of dementia in this population to support or inform clinical diagnoses.MethodThis study extends our epidemiological work, and arose from extensive community consultation and engagement. This engagement included a pilot MRI study (n=14), community planning survey, and guidance from an Aboriginal and Torres Strait Islander Steering Committee. The neuroimaging sub‐study is a prospective, cross‐sectional non‐interventional study. Participants first complete a comprehensive interview and diagnostic assessment as part of the Koori Growing Old Well study. Consenting participants with cognitive decline (diagnosis of cognitive impairment or dementia; n=40) and age/sex‐matched healthy controls (n=40) aged 60+ will undergo MR, FDG PET‐CT and PiB PET‐CT scans. An additional n=120 participants >55 years will be recruited to an MR scan‐only condition.ResultPilot work and consultation showed acceptability of neuroimaging with partnering Aboriginal communities, including 74% of planning survey participants (n=213) indicating that neuroimaging should be included in future dementia studies (Lavrencic et al., 2020, Int Psychogeriatr). Older Aboriginal people living in New South Wales, Australia are currently being recruited; n=20 have undergone PET‐CT and MR scans to date (expected study completion by 2023). Outcome analyses will compare cognitive decline and healthy control groups on a range of measures including amyloid burden, regional glucose metabolism, hippocampal atrophy/volume and vascular indices on MR. Associations between amyloid burden and vascular pathology will be examined for cases of possible/probable Alzheimer’s disease. Correlations between MR measures and early life stress, adult adversity, cognitive function, and clinically diagnosed cognitive impairment will be investigated.ConclusionOur study will, for the first time, investigate functional and anatomical neuroimaging in older Aboriginal Australians and inform dementia prevention, diagnosis and policy for Aboriginal Australians. It will also contribute to the wider literature on vascular risk in the pathogenesis of AD, with associated biomedical and social risk factors across the lifespan of Aboriginal Australians.
Telemedicine in French memory clinics during Covid‐19 crisis
Authors: Morin Alexandre , Pressat‐Laffouilhere Thibault , Sarazin Marie , Lagarde Julien , Roue‐Jagot Carole , Paquet Claire , Cognat Emmanuel , Dumurgier Julien , Pasquier Florence , Lebouvier Thibaud , Ceccaldi Mathieu , Godefroy Olivier , Martinaud Olivier , Grosjean Julien , Zarea Aline , Maltête David , Wallon David 
Published: February 2022

AbstractBackgroundIn early 2020, COVID‐19 outbreak struck France leading to a national lockdown between March 17th and May 11th. While standard in‐person medical consultation was complicated, telemedicine dramatically expanded. In order to evaluate the impact of this unpreceded situation on clinical practice and use of psychoactive drug in dementia care, we conducted a nationwide clinical prospective and retrospective study.MethodDuring the lockdown period, telemedicine patients’ demographic and clinical data were retrospectively collected from 7 French memory clinics (telemedicine cohort). Clinical diagnoses, treatment changes, cognitive modifications since last consultations and living conditions during the lockdown were systematically retrieved.In Rouen site, we also included patients only reached by a secretary to propose a postponed visit after lockdown (no‐telemedicine cohort) and patients seen in 2019 during the same period of the year (Rouen‐2019).The primary outcome was any change in psychoactive drug and a specific analysis on sedative treatment increase was the secondary outcome, defined as any increase in the prescriptions of antipsychotics or benzodiazepines.ResultThe telemedicine cohort included 874 patients (73 from Rouen), while no‐telemedicine control cohort and Rouen‐2019 cohorts included respectively 86 and 234 patients (table 1). In the telemedicine cohort, treatments were modified for 10.7% of the patients with more treatment modification among the patients living with a relative (+5.8% (CI95% [0.2%; 11.4%] p=0.04) and among the patients with Alzheimer’s disease (+12.2% (CI95% [7.1%; 17.3%] p<0.001). When comparing therapeutic strategies in 2020 and 2019 for Rouen site, 24.6% of the patients had their treatment modified in 2020 and 12.4% in 2019. That difference was however not statically significant with an adjusted percentage difference of ‐4% (CI95% [‐10.8%; 3.4%] p=0.27, including the telemedicine and no‐telemedicine cohorts for 2020.ConclusionTelemedicine seems to have had only minor negative impacts on clinical practice in memory clinics.
ATN classification in dementia with Lewy bodies: Association with clinical profile, cognitive decline and survival
Authors: van de Beek Marleen , Ooms Floor A.H. , Ebenau Jarith L. , Barkhof Frederik , Scheltens Philip , Teunissen Charlotte E. , van Harten Argonde C. , van der Flier Wiesje M , Lemstra Afina W. 
Published: February 2022

AbstractBackgroundThe ATN framework has been developed to characterize biological processes within the Alzheimer’s disease (AD) continuum. Since AD pathology often coincides with dementia with Lewy Bodies (DLB), we aimed to examine the distribution of ATN profiles in DLB and associate ATN‐profiles in DLB to prognosis.MethodWe included 192 DLB patients from the Amsterdam Dementia Cohort (68±7yrs, 19%F, MMSE: 24±3, DAT‐SPECT abnormal: 104/114). Patients were classified according to the ATN framework, using CSF Aβ1‐42 (A), CSF p‐tau (T) and medial temporal atrophy scores (N). Categories were compared on presence of clinical symptoms and demographics. To yield sufficient power for longitudinal analyses, the eight profiles were combined into four categories: normal AD biomarkers (A‐T‐N‐, reference), non‐AD pathologic change (A–T–N+/A–T+N–/A–T+N+), amyloid‐only (A+T‐N‐) and amyloid‐plus (A+T–N+/A+T+N–/A+T+N+). We used linear mixed models to analyze decline in MMSE (follow‐up 3±2yrs for n=137). We assessed differences in mortality using Cox proportional‐hazards models.ResultFifty (26%) DLB patients had normal AD biomarkers (A‐T‐N‐), 36 (19%) had non‐AD pathologic change (A‐T+N‐: 10%/A‐T‐N+: 6%/A‐T+N+: 3%) and 106 (55%) were classified within the AD‐continuum (A+T‐N‐: 20%/A+T+N‐: 16%/A+T‐N+: 10%/A+T+N+: 9%)(figure 1). A+T+N+ patients were older and less often had RBD symptoms. Compared to patients with normal AD biomarkers, those with amyloid‐only had steeper decline in MMSE (β±SE=‐0.82±0.28, p=0.005), while amyloid‐plus was associated to higher mortality rate (HR: 1.85[1.09‐3.13]). Cognitive decline and mortality did not differ between non‐AD pathologic change and normal AD biomarkers (figure 2‐3).ConclusionIn our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD‐continuum had steeper cognitive decline (especially amyloid‐only) and shorter survival (amyloid‐plus). Individuals with non‐AD pathologic change did not differ from those with normal AD biomarkers in clinical presentation, decline or survival. Implementing the ATN framework within DLB patients could aid in subtyping patients based on underlying biological processes and provide targets for future treatment strategies, e.g. AD modifying treatment.
Covid‐19 pandemic: A curse and a blessing for informal dementia caregivers — A qualitative study
Authors: Taneska Marija 
Published: February 2022

AbstractBackgroundCaring for a relative or friend who lives with dementia is a complex and demanding process that affects the quality of life and the well‐being of the informal caregivers. Many previous studies show that informal dementia caregivers experience high levels of stress, psychological burden, and depression due to the demands of caregiving which include changes in one's personal and professional life, self‐neglect, and withdrawal from pleasurable activities. The COVID‐19 pandemic drastically changed people's lives and everyday interactions and the limited number of studies on this topic shows that it introduced additional challenges for dementia caregivers. These challenges include protecting themselves and the person they care for from infection, managing the behavioural and psychological symptoms of the disease, introducing changes in everyday routines, dealing with quarantine or isolation.MethodThe aim of this study was to gain a better insight into the experiences of informal dementia caregivers during the COVID‐19 pandemic. Semi‐structured interviews were conducted in the period of July‐September with nine participants from different countries and the data were analyzed using inductive thematic analysis resulting in extraction of five themes.ResultsThe results show that informal caregivers experience worsening of the behavioural and psychological symptoms of the person they care for, limited access to the institutions and the person they care for, fear of infection but also more free time for looking after the person with dementia.ConclusionThis was one of the first qualitative research aimed to understand the unique experiences of informal dementia caregivers during the COVID‐19 pandemic, and the first research ever that has included caregivers from North Macedonia. The results show that informal dementia caregivers experience additional burden and challenges due to the COVID‐19 pandemic which adds to their existing psychological distress. This can further compromise their health and well‐being, and result in lower quality of life for them and the person with dementia and requires more focused attention from the relevant medical and social services. It should also be taken into consideration when constructing policies for dementia management and formal support during the times of the pandemic.
Dementia friendly community outreach improves research participation and dementia resource utilization among African Americans
Authors: Lucas John A , Robinson Maisha T , Bergeron Caroline D. , Willis Floyd B , Parfitt Francine C , Fudge Michelle R , Wainwright Jolita D , Graff‐Radford Neill R 
Published: February 2022

AbstractBackgroundAfrican Americans are at greater risk of Alzheimer’s disease (AD) and AD‐related dementia (ADRD). They are also less likely to access dementia resources or participate in dementia research. The National Alzheimer’s Project Act (NAPA) calls for special attention to dementia‐related health disparities in high risk groups. Identifying effective tools to improve rates of dementia resource utilization and research participation by African Americans is essential to achieving dementia health equity.MethodTwo neighborhoods of Jacksonville, FL, defined by zip codes, were the focus of this study. Both zip codes have a large population of African American residents per 2010 US Census, and a history of hosting outreach activities by our Alzheimer’s Disease Research Center (ADRC). In one neighborhood, we modified the NAPA Dementia Friendly (DF) America toolkit to serve as a model of outreach. The second neighborhood served as a control (CON), in which we maintained our traditional outreach model of community‐based lectures. Primary outcome measures were: (1) enrollment in ADRC center‐related studies and (2) phone call volumes from individuals seeking dementia resource information. The outcomes in the DF and CON neighborhoods were compared via Fisher’s exact test to those in other zip codes in Jacksonville (OT).ResultIn the 18 months following implementation of the DF intervention, 54 African Americans enrolled in ADRC‐related research (19 DF, 3 CON, 32 OT), compared to 21 during the 18 months prior (2 DF, 0 CON, and 19 OT). The increase in DF residents enrolling in research following the intervention was statistically significant (p =0 .02) relative to OT residents. The increase observed in the CON residents was not statistically significant (p=1.0) compared to OT residents. Call volumes from African Americans increased from 13 prior to program implementation (all from OT) to 62 calls after implementation (22 DF, 1 CON, 39 OT). The increase among DF residents seeking information following the intervention was statistically significant (p =0.008) whereas the increase was not significant in the CON residents (p=0.54).ConclusionResults suggest that the NAPA DFA can be leveraged to improve dementia resource utilization and research participation among community‐dwelling African Americans.
Interstitial fluid as a proxy of glymphatic dysfunction in patients with cognitive impairment: The necessity of three‐directional intravoxel incoherent motion
Authors: Thiel Merel M. , Freeze Whitney M. , Jong Joost J. , Ramakers Inez H.G.B. , Backes Walter H. , Jansen Jacobus F.A. 
Published: February 2022

AbstractBackgroundIntraVoxel Incoherent Motion (IVIM) MRI can detect an intermediate diffusion component, which is thought to be related to increased interstitial fluid (ISF). However, IVIM imaging with a proper estimation of the diffusion tensor requires a long acquisition time (∼10 min), which is not feasible in clinical practice. This study simultaneously examines the contribution of individual diffusion directions and the potential group differences between patients with Alzheimer’s disease (AD), mild cognitive impairment (MCI), and cognitively normal controls (CN). We foresee to find a higher ISF‐fraction in patients compared with controls, as underlying pathologic processes, e.g. inflammation and oedema, would ultimately lead to loss of tissue structure and increase in ISF.MethodPatients with AD dementia (n=15) and MCI (n=15), and 33 CNs underwent 3T MRI. IVIM images were acquired with a range of b‐values (10‐1000 s/mm2) in three orthogonal diffusion directions: M (left‐right), P (anterior‐posterior) and S (superior‐inferior) (Fig. 1).The intermediate diffusion components (Dint) in the range 1.5<Diffusivity<4.0*10‐3 mm2/s, for each direction and average (trace) diffusion images were calculated with spectral analysis and the relative signal contribution of Dint was quantified by the ISF‐fraction (fint). The median values of the parenchymal diffusivity (Dpar), Dint and fint were extracted from the normal appearing white matter and corpus callosum.Per brain region, the fint, Dpar and Dint values were compared between the subject groups using multivariate linear regression while correcting for age and sex.ResultGroup characteristics and descriptive statistics are shown in Table 1 and 2. Table 3 contains all significant group differences of fint, Dpar, and Dint, derived by the M, P, S and trace images, which shows a higher fint in patients than in CNs. Similar group differences in fint can be obtained from the M‐direction and the trace (Fig. 2)ConclusionA higher ISF‐fraction was found in AD patients as compared to CNs, which is expected to point out tissue degeneration. The ISF‐fraction assessed with spectral analysis in IVIM can be considered as a potential non‐invasive biomarker related to glymphatic alterations in brain disease. As the M‐direction was sufficiently sensitive to determine differences in ISF fraction, more clinically acceptable acquisition times can be achieved.
Baseline amyloid and tau PET imaging characteristics in the ongoing phase 2 study of tilavonemab in early Alzheimer’s disease
Authors: Wooten Dustin W. , Guo Qi , Jin Ziyi , Gladstein Scott , Stage Edwin , Hesterman Jacob , Fisseha Nahome , Florian Hana , Comley Robert A. 
Published: February 2022

AbstractBackgroundAmyloid and tau are recognized hallmarks of Alzheimer’s disease (AD). Tilavonemab is a monoclonal antibody that binds to the N terminus of human tau and is being developed as a treatment for early AD. The goal of this work is to present the baseline amyloid and tau PET imaging characteristics of patients enrolled in the ongoing phase 2 study of tilavonemab.Method453 patients who met the clinical criteria for early AD and had a positive amyloid PET scan (by visual read) at screening were randomized into the study. Amyloid PET was quantified on the standard Centiloid (CL) scale utilizing a processing pipeline developed in‐house and validated using recommended procedures [Klunk, et al., 2015]. Tau PET imaging using 18F‐MK6240 was also performed in a subset of patients to assess presence of tau pathology, the target of tilavonemab, and to monitor disease progression and treatment effects. Here we report baseline tau PET data from 59 subjects randomized into the trial (out of 70 scans collected, not including screen fails or out of baseline window scans). Tau PET was quantified in Braak regions I‐VI using standardized uptake value ratio (SUVR), extent (percentage of voxels within a region above threshold) and load (extent * mean SUVR of voxels within a region above threshold) metrics. Ventral cerebellar gray matter was used as a reference region for SUVR calculation and to determine the subject‐specific threshold needed for the extent and load calculation.ResultOver 99% of subjects (449/453) had amyloid measurements greater than 20CL, a threshold used for positivity [Burnham, et al., 2020], consistent with visual read; mean±s.d. was 99.0±31.1 CL. For the 59 patients with baseline tau PET data 95% (56/59) were considered to have elevated tau pathology in the brain (SUVR ≥1.27 in the entorhinal cortex [Betthauser, et al., 2020]). The tau metrics for Braak regions I‐VI are summarized in Table 1.ConclusionThis analysis confirmed the presence of amyloid pathology in the patients randomized into the trial and suggested a high proportion of patients have tau pathology in the brain. Future analyses will examine how tilavonemab effects tau pathology.
Impact of COVID‐19 on family care partners of persons with dementia in long‐term care settings in Canada: Not a ‘one‐size‐fits‐all’ story
Authors: McAiney Carrie A , Boger Jennifer , Conway Emma , Koch Melissa , Beleno Ron , Boscart Veronique , Dupuis Kate , Dupuis Sherry L , Keller Heather , Kuepfer Jane , Lee Linda , Lopez Kimberly , McKinnon Margaret , Taucar Linda Sheiban 
Published: February 2022

AbstractBackgroundCOVID‐19 has been devastating for older adults, particularly residents in long‐term care/retirement (LTC) homes. In an effort to curb the transmission of COVID‐19, public health measures have been put in place in many LTC homes, including mask wearing, physical distancing, and visitor restrictions. As the pandemic passes the one‐year mark, we are starting to understand the profound impacts of COVID‐19 and the corresponding public health measures on persons living with dementia (PLWD) and their family care partners (CPs). This research is part of a larger study exploring the impact of COVID‐19 on the wellbeing and social connections of PLWD and CPs. In this presentation, findings from qualitative interviews conducted with CPs of PLWD in LTC homes are shared.MethodsThe overall study used an intrinsic case study design, involving survey and interview data. Following completion of a survey, participants were invited to participate in an in‐depth qualitative interview. Interviews were conducted by phone or online, transcribed verbatim, and analyzed using thematic analysis.ResultsEighteen CPs were interviewed. The impact of visitor restrictions varied between LTC homes and changed over the course of the pandemic, which was extremely challenging for CPs. At homes with visitor restrictions, the inability to visit family members with dementia was described as stressful, unfair, and frustrating. CPs stressed the importance of being able to visit their relatives, and ensuring their family members had regular social interaction to support their physical, social and emotional wellbeing. Even when CPs could visit, masks and physical distancing made communication with some PLWD challenging. Visitor policies also influenced perceptions of care. Some CPs felt that the needs of their family members with dementia were being met by the home, while others weren’t sure because CPs weren’t in the homes to assist staff and provide support to their family members with dementia.ConclusionWhile COVID‐19 and the pandemic restrictions have been difficult for all CPs of persons with dementia in LTC, for some it has been agonizing. Understanding these varied experiences can help inform the development of individually‐tailored resources to better support the wellbeing of CPs.
Modeling resting state MEG functional connectivity of the prodromal phase of AD using The Virtual Brain
Authors: Susi Gianluca , Méndez Isabel Suarez , Verdejo Juan , García María Eugenia López , Cuesta Pablo , Maestú Fernando 
Published: February 2022

AbstractBackgroundComputational multi‐scale brain modeling has been found to be a useful tool for identifying potential disease mechanisms in Alzheimer's disease (AD) [1]. Importantly, structural and functional disruption patterns of AD continuum arise from a chain of degeneration effects which take place even from the preclinical phase of the disease, which characterization has the potential to enable early intervention to counteract and delay cognitive decline.MethodMagnetoencephalography (MEG), T1‐ and dw‐ magnetic resonance imaging (MRI) have been gathered from 20 healthy controls (HC) and 20 mild cognitive impaired (MCI), to characterize their resting‐state functional connectivity (rsFC), and structural connectivity (SC) profiles. Regarding MEG signal, source reconstruction was performed with linearly constrained minimum variance beamformer and the obtained neural MEG sources were anatomically parcellated according to the Desikan‐Killiany atlas. Resting state activity of the participants has been characterized considering two FC indices (i.e., PLV and AEC) among relevant areas of the Default Mode Network (DMN). Personalized simulations of the 40 subjects have been carried out using The Virtual Brain software and the matching between real and simulated rsFC is finally evaluated. For the MCIs two different degradation patterns are introduced in the model, one based on the gray matter volumes, and one that takes in account white matter integrity.ResultThe inclusion of both types of degeneration patterns in key areas of the DMN results in an increase of the matching between real and simulated rsFC for MCI patients; the inclusion of both simultaneously brought the best results.ConclusionThis study shows how the inclusion of quantifiable signatures of structural degeneration regarding gray matter volumes and white matter integrity in multi‐scale brain models reflects to a better matching between real and simulated MEG‐rsFC, when modeling MCI patients. This complements the already existing studies in the field and provides new insights towards a precise characterization of patient's MEG resting state networks during the early phases of AD. 1 ‐ L. Stefanovski et al., “Linking Molecular Pathways and Large‐Scale Computational Modeling to Assess Candidate Disease Mechanisms and Pharmacodynamics in Alzheimer’s Disease,” Front Comput Neurosci, vol. 13, p. 54, 2019.