bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurite density and free water concentration are associated with synaptic density in the hippocampus as assessed through NODDI and [C‐11]UCB‐J PET
Authors: Kohli Akshay , DiFilippo Alexandra H. , Gallagher Rigina L. , Davenport Nancy J. , Betthauser Tobey J. , Johnson Sterling C. , Christian Bradley T. , Bendlin Barbara B. 
Published: February 2022

AbstractBackgroundNeurite Orientation Dispersion and Density Imaging (NODDI), derived through multi‐shell diffusion MRI, allows for the estimation of markers pertaining to multiple distinct components of neural tissue microstructure. Lower neurite density index (NDI), lower orientation dispersion index (ODI), and higher volume fraction of isotropic water (Viso), have all been significantly associated with biomarkers of AD pathology, as well as increase diagnostic model predictability. Recent studies employing [C‐11]UCB‐J PET to study synaptic vesicle glycoprotein 2A (SV2A) have found strong reductions in individuals with AD. Here we explore regional associations between cortical tissue microstructure (indexed by NODDI) and synaptic density (measured through [C‐11]UCB‐J PET). We hypothesize that increased NDI and ODI, and decreased Viso will associate with higher [C‐11]UCB‐J binding.MethodParticipants (N=24) included cognitively unimpaired and impaired older adults (Table 1) from the Wisconsin Alzheimer’s Disease Research Center who underwent [C‐11]UCB‐J PET and multi‐shell diffusion MRI. NODDI measures (including NDI, ODI, and Viso) were estimated and [11‐C]UCB‐J binding was quantified by calculating distribution volume ratios (DVR) using SRTM2 with the whole cerebellum as a reference region. Pearson correlations were conducted within Desikan‐Killiany‐derived regions of interest (ROI) including the hippocampus, entorhinal cortex, and parahippocampal gyrus, regions previously associated with altered NODDI metrics and [C‐11]UCB‐J binding in the AD population.ResultSignificant associations were found between [C‐11]UCB‐J DVR and both NDI and Viso in the hippocampus (NDI: r = 0.45, p=0.047; Viso: r = ‐0.46, p = 0.043). A trend was identified between [C‐11]UCB‐J DVR and ODI in the parahippocampus (r = 0.39, p = 0.098). No significant associations or trends were found in the entorhinal cortex.ConclusionThis preliminary analysis identified associations between increased synaptic density and metrics of cortical tissue microstructure. Both NDI and Viso were correlated with [C‐11]UCB‐J DVR in the hippocampus, indicating dendritic complexity and synaptic density are possibly linked. Future analyses will include more participants, determine whether hippocampal [C‐11]UCB‐J DVR in addition to NODDI may increase diagnostic model predictability, as well as estimate the temporal progression of synaptic and dendritic loss in AD.
The Brain Health Champion study: A health coaching intervention with mobile technology in older adults with mild cognitive impairment or risk factors for dementia
Authors: Krivanek Taylor , McFeeley Brittany , Nicastri Casey M , Babazadeh Demsina , Daffner Kirk R , Gale Seth A 
Published: February 2022

AbstractBackgroundThere is growing evidence that adherence to brain‐healthy behaviors can reduce the rate of cognitive decline and risk of dementia. We previously demonstrated that a health coaching intervention, including weekly phone calls, facilitated adherence to these lifestyle recommendations in older adults with mild cognitive impairment (MCI) or mild dementia. The current study extends this research by including cognitively normal, at‐risk older adults and adding technologies, including a mobile health platform and wearable fitness trackers, to the health coaching intervention.MethodParticipants, age 60‐79, with MCI or dementia risk factors are being randomized to the Brain Health Champion (BHC) intervention or a counseling and education (CE) control. In BHC, with guidance from a health coach, participants set personalized goals, reinforced by weekly video calls, mobile messaging, one dietitian consult, and 30‐minute in‐person or virtual visits every six weeks. In CE, educational materials sent every six weeks supplement usual care. Changes in physical activity, diet, social/cognitive engagement, neuropsychological test scores, and metrics of behavioral health are being measured over a six‐month intervention period using validated questionnaires, wearable fitness trackers, and photographed food logs. Maintenance of behavior changes is also being assessed six months post‐intervention.ResultTwenty participants have been enrolled in the study, with five BHC and six CE participants completing it to date. All participants successfully operated the mobile technology by themselves or with caregivers’ assistance. Data trends show that BHC participants had numerically increased scores on neuropsychological tests, cognitive activities, and photographed Mediterranean diet adherence compared to CE participants. Participation in the study, regardless of program, was associated with increased self‐reported Mediterranean diet adherence. Participants also reported enjoying their respective programs. Four of five BHC participants and four of six CE participants said that they would like if their program was implemented into their regular care. All but one participant reported foreseeing their program having a lasting impact on their health and wellbeing.ConclusionOlder adults with MCI or dementia risk factors are able to manage the requirements of either the BHC or CE program. Trends in the data indicate that the BHC program is particularly well‐suited for promoting adherence to brain‐healthy behaviors.
The use of artificial intelligence and machine learning in the care of patients with dementia: A literature review
Authors: Belam Georgia , Nilforooshan Ramin 
Published: February 2022

AbstractBackgroundThe question as to how best to help people living with dementia, and their carers, is an ever pressing global health and social care concern. Emerging technologies may have the potential to help with this and we decided to perform a literature review on the existing research.ObjectivesTo identify, appraise and synthesise the literature to assess the existing research landscape of the area of machine learning and artificial intelligence, with relation to the care of people with dementia.MethodsA literature search was conducted, searching the PsychInfo, Medline, PubMed and Embase databases. With the papers identified, we assessed the quality of the research and considered what overall findings there were in the existing literature.Results619 papers were initially identified, of which 28 related to the use of AI and machine learning in the care of people with dementia. The papers were divided into categories to show the utility and effectiveness these technologies may have: 1: to alert caregivers and professionals to problems that people with dementia may have 2: to facilitate activities and treatment for people with dementia, both health and social care related 3: to help decide on and plan care for people with dementia 4: to consider the ethical implications of the use of artificial intelligence and machine learning in this patient groupConclusionThere is a paucity of literature about the use of AI and machine learning in dementia care, but the existing studies show some potential, if used well, for these technologies to be a useful addition to the care of people living well with dementia. In particular there is potential for the use in terms of location sensors which may in the future assist with helping to keep patients safe. As is always the case with technology as applied to medicine, the experience of people living with dementia and their carers must be integral to their development and use.
Automatic prediction of cognitive and functional decline using baseline MRI and cognitive scores
Authors: Shafiee Neda , Dadar Mahsa , Ducharme Simon , Collins Louis 
Published: February 2022

AbstractBackgroundPatients in the early stages of AD dementia experience decline in their cognitive abilities at different rates. Accurately predicting the progression rate would enable the enrichment of patient populations in clinical trials. Using the early AD‐related pattern of atrophy and cognitive scores from a baseline visit, we trained a model to predict cognitive and functional decline in early stages of AD.MethodData included 312 patients with mild Alzheimer’s disease from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset and were chosen based on amyloid positivity, the Clinical Dementia Rating (CDR=0.5) and the Mini‐Mental State Exam (MMSE, range 24‐30) scores. SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure AD‐related atrophy patterns in the hippocampi (HC) and entorhinal cortex (EC) (Coupé et al. 2019). A balanced random forest was used to train models with feature sets including MR‐based z‐scored features (SNIPE scores for HC and EC), and cognitive test scores (Alzheimer’s Disease Assessment Scale (ADAS‐13), MoCA (Montreal Cognitive Assessment), and MMSE) from baseline data. Classifiers were trained using different combinations of features plus age. The classification performance was evaluated based on the measured sensitivity, specificity, and accuracy to predict future functional and cognitive decline (defined as a 2‐point change in CSD‐SB).ResultTable 1 shows the classification performance of all trained models for two and three year follow up periods. Using hippocampal grading scores in addition to MoCA, ADAS‐13 and MMSE, yields the highest accuracy (76.9%) in predicting cognitive decline at 2 years. Figure 1 shows the ROC curve for two models: One consisting of all cognitive features and the other using both cognitive and MRI features. Comparing results between the classifier using only the baseline cognitive score and the corresponding classifier with the added MRI features showed that for both follow‐up periods, the accuracy of prediction is increased when adding MRI features.ConclusionMicroscopic changes due to AD pathology that occur in the HC and EC can be used as a feature in a predict the cognitive decline and increase the accuracy of prediction, even at the early stages of the AD trajectory.
The challenges of aging in place for older adults at risk of self‐neglect and expectations regarding smart environments: Perspectives of older adults and their caregivers
Authors: Aboujaoudé Aline , Couture Mélanie , Moreau Maxim , Lussier Maxime , Laliberté Catherine , Bottari Carolina , Giroux Sylvain , Belchior Patricia , Paré Guy , Bier Nathalie 
Published: February 2022

AbstractBackgroundSelf‐neglect is a behavior found in older adults with cognitive deficits. It manifests through the refusal, or inability, to care for themselves and puts them at higher risk for institutionalization. In Quebec, administrators in home care services are increasingly open to offering smart environments as part of their services to this clientele as it can help identify unfulfilled needs. However, little information is available about the implementation of technology in home care services, including the perspective of this clientele and their family. An embedded case‐study was conducted to provide insight on their perception of obstacles for home care and their expectations of technological solutions.MethodThrough individual interviews, qualitative data regarding the perspectives of older adults at risk of self‐neglect (n = 5) and their caregivers (n = 3) was collected in regard to: 1) current obstacles at home; and 2) expectations toward technology to optimize their functional autonomy. Data was analyzed using the approach of Miles, Huberman and Saldana.ResultDespite the fact that some older adults (n = 3) presenting self‐neglect perceive themselves as functioning well at home and not needing more help than they already receive from home care service, all older adults (n = 5) perceived risks in their home environment and described difficulties with their memory (e.g. forgetting appointments) and mobility (e.g. falls). Similar difficulties were described by their caregivers, who also perceived some risks with remaining at home due to a deteriorating functional capacity. With respect to technology, it was identified that it could support the autonomy of the older adults in some aspects, but not replace current home services available. Technology also had to be easy to use and learn.ConclusionThis study suggests that older adults at risk of self‐neglect and their caregivers believe that technology can support aging in place but in combination with other solutions. When implemented, technology should be adapted to the needs, values, and preference of clients and their family, to address as many of the individual’s perceived risks as possible.
Association of enlarged perivascular spaces (ePVS) and MRI markers of small vessel disease (SVD) and neurodegeneration in the Florida Vascular Imaging Phenotypes (FL‐VIP) Study of AD Risk
Authors: Haq Ihtsham U. , Del Brutto Andrade Victor , Goryawala Mohammed , Saporta Anita Seixas Dias , Merritt Stacy S. , Camargo Christian , Agudelo Christian , Ariko Taylor , Dong Chuanhui , Loewenstein David , Duara Ranjan , Rundek Tatjana 
Published: February 2022

AbstractBackgroundPVS are fluid filled compartments surrounding small intracerebral vessels. They are conduits for fluid transport, exchange, and waste clearance. ePVS are observed in AD, but their relation to SVD markers and neurodegeneration is unknown. We tested whether ePVS are correlated with markers of SVD but not cortical atrophy.MethodWe analyzed subjects’ brains from the FL‐VIP (comprised of all 1Florida ADRC participants with high quality 3T MRI). ePVS were defined as parenchymal hypo/hyperintensities of <3 mm seen on a single axial T1,T2, or FLAIR section through the basal ganglia (BG) and centrum semiovale (CSO). ePVS were graded as 0 (none), 1 (<10), 2 (11‐20), 3 (21‐40), and 4 (>40). The side with highest ePVS count was graded. BGBG and CSO scores were summed to yield a 0‐8 ePVS total. Generalized linear models were used to estimate ePVS score associations with White‐Matter Hyperintensity Volume (WMHV), silent brain infarcts (SBIs), cerebral microbleeds (CMBs), and mean total cortical thickness. We adjusted for demographics, vascular risk factors and comorbidities, and ApoE4 status.ResultOf 228 non‐demented participants (mean age 72±8 years; 61% women, 60% Hispanic, mean education 15±4 years, 33% ApoE4 carriers), 59% were hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. 73% of subjects had a total ePVS score >1. Scores ranged from 0‐7 total (mean 2.5±1.4), 0‐4 for BG (mean 1.3±0.7) and CSO (1.2 ±0.9). In unadjusted analyses, total ePVS correlated with WMHV (r=0.46, p<0001), SBI (r=0.17, p=0.009), and CMB (r=0.16, p=0.016). BG ePVS correlated with WMHV, SBI and CMB. CSO ePVS correlated only with WMHV (r=0.32, p=0.002). In multivariable analyses, ePVS correlated with WMHV (β=4.97, p<0.001), SBI (OR=1.36, p=0.027), and CMB (OR=1.43, p=0.019). BG ePVS remained associated with WMHV, SBI and CMB; and CSO ePVS only with WMHV (β=4.70, p=0.039). Total, BG, and CSO ePVS were not associated with cortical thickness.ConclusionBG ePVS are highly related to MRI markers of SVD, but not total cortical thickness, and therefore may be considered hallmark features of small vessel disease. CSO ePVS may not have as a prominent role in SVD.
Decreased purine metabolite levels in cerebrospinal fluid of transgenic cerebral amyloid angiopathy rats
Authors: van den Berg Emma , Van Nostrand William E. , Peters Tessa M.A. , de Boer Siebolt , Coene Karlien L.M. , Engelke Udo F.H. , Kuiperij H. Bea , Verbeek Marcel M. 
Published: February 2022

AbstractBackgroundCerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhages and contributes to cognitive decline. The currently applied modified Boston criteria fall short in detecting early‐stage disease and biomarkers to track disease progression are lacking. In the CAA Fluid Biomarker Evaluation (CAFE) study we aim to identify novel CAA‐specific biomarkers. We hypothesize that levels of metabolites in cerebrospinal fluid (CSF) are altered due to amyloid‐β deposits.MethodHigh‐resolution liquid chromatography quadrupole time‐of‐flight mass spectrometry was used to analyze metabolite levels in an untargeted fashion (Coene et al., 2018; Peters et al., 2020) in CSF derived from small‐vessel CAA transgenic (rTg‐DI) and wild‐type (WT) rats. Candidate features identified in a discovery study (n=8 WT; n=10 rTg; 6 months old) were validated in larger groups of rats including various ages (n=30 WT; n=29 rTg; 3‐6‐12 months old). Features were annotated based on accurate mass, specific retention time and semi‐quantitative intensity by comparison with reference standard compounds and online database matching.ResultOf the 48 significantly different features discovered in the pilot, 27 could be validated in the second study. Several features corresponded with reference compounds of metabolites involved in the purine metabolism pathway, which included guanosine, guanine, inosine, xanthine and hypoxanthine. All these levels were significantly decreased in all groups of the rTg rats compared to WT, some progressing with older age (Figure 1). An additional n=605 features were identified with significantly different levels between the various groups. Molecular formulas for other possible interesting features could be computed, whose metabolite identities are currently being confirmed by using standard compounds.ConclusionMetabolomics analyses of the CSF of transgenic rats shows promise in discovering novel potential biomarkers for CAA. Using a robust animal model allows us to study biomarkers along the trajectory of disease progression. Our results suggest a global down‐regulation of the purine pathway (Figure 2), a finding previously observed in early‐stage Alzheimer’s disease (Alonso‐Andrés et al., 2017).
Engaging people with lived experience in peer review: Expanding the role of citizen reviewers
Authors: Jaggers Kaitlyn , Badali Jocelyn , Guimond Josée , Sivananthan Saskia 
Published: February 2022

AbstractBackgroundResearch shows that including the voices of people with lived experience (PWLE) in the full research process ensures that the research is both relevant and meaningful in real‐life contexts. However, operationalizing this in a meaningful way can be challenging, particularly in the context of dementia. Since 2014, the Alzheimer Society of Canada (ASC) has included PWLE in the Alzheimer Society Research Program’s (ASRP) peer review process through the role of the citizen reviewer, however, this has been limited in scope. In 2019, a pilot study expanded this role to a broader panel of citizen reviewers who are equal participants in the peer review process, scoring applications and providing valuable contextual feedback. In 2020, this process was further formalized, allowing greater participation and enhanced engagement.MethodQualitative feedback was collected from panelists following the 2019 pilot which demonstrated a collective desire to improve overall engagement while formalizing a systematic process. The data was thematically assessed and used to create several resources to recruit, maintain, and train citizen reviewers as equal and valued participants in the peer review process. This was conducted within the context of the pandemic, in which the full process was adapted to a virtual peer review process.ResultData from the 2019 pilot resulted in a four‐step process for recruitment, orientation, and training of citizen reviewers. Semi‐structured interviews were conducted with potential candidates, followed by a comprehensive orientation package, and a virtual orientation session designed for PWLE that included role playing and case studies. Lastly, technical support meetings were created to support the virtual nature of the process. Twenty‐five citizen reviewers were recruited, an increase of 44% participation from the previous year. This, in turn, has led to the creation of a new resource guide for engaging PWLE in peer review, which demonstrates how to operationalize meaningfully engaging and valuing the experiences of people living with dementia.ConclusionThe pilot and subsequent expansion of the citizen reviewer role has created a new way to operationalize lived experiences within the research funding process. While requiring significant upfront work, the value of real‐life experience in prioritizing research is unparalleled.
Diversity considerations of white matter hyperintensities and connectivity in normal aging and MCI
Authors: Misiura Maria , Igwe Kay , Howell J. Christina , Tannahill Amber , Brickman Adam M. , Turner Jessica A. , Hu William T. 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) is twice as likely to occur in African Americans than in Non‐Hispanic Whites. However, current neuroimaging models of AD do not accurately overlay onto the African American profile of this disease. One variable that could contribute to more accurate modeling is the inclusion of vascular factors into models of AD, as African Americans are more likely to have vascular as well as AD. Functional MRI is a widely used method to measure brain activity in individuals with AD. Connectivity in the form of correlated between regions can be used to determine neurological dysfunction. Fronto‐striatal connectivity, while understudied in AD, has shown to be affected by AD and vascular disease. This study attempts to determine if there are connectivity measures that relate to vascular lesions(White Matter Hyperintensities (WMH)) across the disease spectrum, and whether these relationships are uniform across race.MethodWe analyzed data from 88 people (54= NC, 34=MCI). We conducted functional connectivity using DPARSFA toolbox with connectivity calculated between the following fronto‐striatal regions within each hemisphere: anterior putamen, middle frontal gyrus, superior frontal gyrus (putamen output regions), pre‐ and postcentral gyri (putamen input regions). To calculate regional white matter hyperintensity we used in‐house code to overlay a regional atlas onto a WMH mask extracted from a T2 weighted FLAIR image, and assigned a score to each individual representing load (0=no WMH in any regions, 1=WMH in 1 or the other region, 2=present in both regions.ResultAcross race and diagnostic categories, WMH were related negatively to right anterior putamen connectivity to the pre and post central gyri such that as WMH load increased, connectivity also decreased. This relationship continued for connectivity measures between the right anterior putamen and the superior and middle frontal gyri, but only within African Americans.ConclusionFronto‐striatal connectivity did correlate with regional WMH load in a uniform manner across races for cortical input regions to the putamen, and this relationship extended to Africans Americans within cortical output regions. This relationship was identified across diagnostic categories, and could be useful in studies investigating vascular relationships to AD biomarkers.