bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered local gyrification index and corresponding functional connectivity in Alzheimer disease
Authors: Zhao Hui , Shao Peng Fei 
Published: February 2022

AbstractBackgroundCortical gyrification is a promising surface anatomical marker to study Alzheimer disease, however, few studies combined the gyrification and functional connectivity together to explore the Potential mechanism in Alzheimer disease.MethodThe study consisted of three groups, healthy control(n=37), Mild cognitive impairment(n=39), and Alzheimer disease(n=30). Comparison between groups of gyrification was performed using ANOVA within CAT12 and SPM 12, age and cortical thickness were returned as covariates. After the LGI analyses, the surface areas with changed LGI were taken as seed regions for functional connectivity (FC) analyses. Comparison between groups of FCs was performed using ANOVA within dpabi 4.3 and RESTplus; age was returned as a covariate. False discovery rate (FDR)‐corrected and P < 0.05 was considered statistically significant.ResultCompared with NC and MCI group, we found significantly decreased LGI(local gyrification index) in left insula and right insula, and the changed LGI in bilateral insula was negatively correlated with disease onset age and positively correlated with global cognitive scores. The following functional connectivity analyses identified decreased functional connectivity between right insula and middle temporal gyrus. The decreased functional connectivities were correlated with disease duration, and global cognitive scores.ConclusionOur findings revealed abnormal LGI in bilateral insula and the connectivity between right insula and middle temporal gyrus maybe used as imaging metrics of Alzheimer disease.
How do tau PET and amyloid PET imaging markers correlate to changes in grey matter microstructure as detected by diffusion MRI?
Authors: Kullakanda Durga Prasad , Chen Jenny , Ades‐Aron Benjamin , Osorio Ricardo , Fieremans Els 
Published: February 2022

AbstractBackgroundDiffusion MRI (dMRI) allows non‐invasive mapping of microstructural changes in the brain. In this study, we assess the relationship between amyloid and tau deposition and grey matter microstructure as detected with diffusion kurtosis imaging (DKI) [1,2]. We hypothesize that inflammation associated with amyloid deposits might result in more restricted diffusion and neuronal death associated with tau pathology might result in less restricted diffusion.Method38 cognitively healthy subjects received 3‐T PET‐MR imaging, each including anatomical MPRAGE, DKI and static PET scans either with 18F‐Florbetaben (n=20, 12 females, age = 67.20±5.75 years) or 18F‐MK‐6240 tracer (n=18, 14 females, age = 66.56±5.23 years) to probe amyloid or tau deposition, respectively. For each subject, regions of interest (ROIs) were automatically segmented on MPRAGE using Freesurfer, combined and narrowed down to 4 regions of interest: primary motor cortex as a control, anterior/posterior cingulate cortex as high amyloid regions, and entorhinal cortex as a high tau region. The standardized uptake values in these ROIs normalized to grey matter cerebellum yielded cortical relative SUV (SUVR). DKI processing provided parametric maps of the mean diffusivity (MD), kurtosis (MK) and fractional anisotropy (FA). Pearson correlation between tau PET SUVR/amyloid PET SUVR and MD, FA, and MK was calculated with significance testing.ResultCorrelation analysis (Tables 1, 2) showed positive correlations between amyloid PET SUVR and MD in posterior cingulate cortex, tau PET SUVR and MD in anterior cingulate cortex and posterior cingulate cortex, and tau PET SUVR and MK in primary motor cortex. Negative correlation was observed between PET SUVR and FA in entorhinal cortex.ConclusionIncreased amyloid and tau burden on PET correlated with less restricted diffusion as indicated by higher MD and lower FA, suggesting sensitivity of dMRI to cortical atrophy and late‐stage neuronal death, as previously observed in cortex and white matter tracts [2, 3]. The current study of healthy controls is limited by the narrow range of amyloid and tau burden. Future work will extend to subjects with mild cognitive impairment. References: [1] Jensen & Helpern, NMR Biomed., 2010(23):698‐710; [2] Dong et al, Neurobiol. Aging 2020(89):118‐128; [3] Montal et al, Alzheimer’s Dement., 2017(14):340‐351.
Formal and informal care use over the course of dementia among adults with limitations in daily activities
Authors: Choi HwaJung , Langa Kenneth M , Norton Edward C , Cho Tsai‐Chin , Connell Cathleen M 
Published: February 2022

AbstractBackgroundThe dynamics between formal and informal care among persons with an activity limitation may substantially differ over the course of their cognitive decline.MethodBased on a nationally representative study of older adults, the sample included 3,685 adults (11,856 year‐persons) who had at least one activity of daily living (ADL) limitation at the time of interview and transitioned to dementia between the years of 1998 – 2016. We estimated probabilities of using formal care and informal care in the years prior to and over the course of dementia, after controlling for sociodemographic factors, survey mode, and proxy interview status.ResultAmong study participants with an ADL limitation, the probability of receiving care from an informal helper increased before the onset of dementia: 36% (95% CI 32‐40) in 4 years prior to the onset (T=‐4); 46% (95% CI 43‐50) at T=‐2; and 48% (95% CI 46‐51) at T=0 (onset); the likelihood of receiving care changed very little over the subsequent years of dementia. In contrast, changes in the probability of receiving formal care are pronounced primarily at the onset of dementia. For example, the probability of overnight nursing home stay was significantly greater at the onset of dementia compared to the years prior to the onset: 12% (95% CI 10‐15) at T=‐2 vs. 31% (95% CI 28‐34) at T=0; this increased over the subsequent years of dementia (e.g., 39% at T=6; 95% CI 34‐43). The probability of receiving nursing home care at the onset of dementia was significantly greater for women vs. men (e.g., Adjusted risk ratio (ARR)=1.21; p=0.010); non‐Hispanic white vs. Hispanic (e.g., ARR=1.62; p=0.004); those with low wealth vs. high wealth (e.g., ARR=1.60; p<0.001); those without a spouse vs. with a spouse prior to the onset (e.g., ARR=1.39; p<0.001); and those with all adult children living far vs. at least one coresident adult child prior to the onset (e.g., ARR=1.51; p=<0.001).ConclusionPublic policies and interventions aimed at planning and providing for the needs of people with dementia should consider disparities in care use over the course of dementia and the potential role of economic resources and family care availability.
A disbalance of matrix metalloproteinases and their inhibitors in the cerebrospinal fluid from patients with cerebral amyloid angiopathy
Authors: Kuiperij H. Bea , Vervuurt Marc , de Kort Anna M. , Kersten Iris , Marques Tainá M. , Schreuder Floris H.B.M. , Klijn Catharina J.M. , Verbeek Marcel M. 
Published: February 2022

AbstractBackgroundMatrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in extracellular matrix (ECM) modelling and regulation of basement membrane integrity. A chronic disbalance in the expression and activity of these proteinases and their inhibitors in favor of MMPs can lead to excessive degradation of the ECM, dysfunction of the blood‐brain barrier (BBB) and subsequent (micro)bleeds. Cerebral amyloid angiopathy (CAA) is characterized by accumulation of the amyloid‐β (Aβ) protein in cerebral vessel walls and decreased BBB integrity, and is a major cause of intracerebral hemorrhage and cognitive decline. Currently, diagnosis of CAA is based on neuroimaging, but there is a need for alternative methods as these neuroimaging methods are not optimal for detection of CAA during life at an early stage. Previously, Aβ40 levels in the cerebrospinal fluid (CSF) have been suggested as promising biomarker for CAA. We hypothesize that a disbalance in MMP/TIMP expression is associated with CAA and is reflected in the CSF, and may besides Aβ40, be a potential biomarker candidate for detection of CAA at an early stage. In this study, we aimed to quantify levels of MMPs, TIMPs and Aβ proteins in the CSF to gain more insight in the pathophysiology of CAA and to establish their potential biomarker value for CAA.MethodWe used immunoassays to quantify MMP‐14, TIMP‐1 and Aβ40 levels in CSF in a group of controls (n=40) and CAA patients (n=28).ResultThe MMP‐14/TIMP‐1 ratio was decreased in CAA (0.016 ± 0.005) vs. controls (0.022 ± 0.008; p=0.0007), which was a stronger difference than observed for either MMP‐14 (not significant: p=0.53) or TIMP‐1 (p=0.0027) alone, or for Aβ40 (p=0.038). The difference of the MMP‐14/TIMP‐1 ratio was robust and remained after correction for age and total protein levels.ConclusionOur results suggest that a disbalance in the expression of MMP‐14 and TIMP‐1 in CSF is associated with CAA, and may be a promising biomarker both to identify CAA, with a higher diagnostic value than CSF Aβ40, as well as to obtain more insight into the pathophysiological processes in CAA.
Comparing drawing under instructions with image copying for mild cognitive impairment (MCI) or dementia screening: A meta‐analysis of 92 diagnostic studies
Authors: Bat Baker Kwok Kwan , Chan Joyce YC , Chan Tak Kit , Huo Zhaohua , Yip Benjamin HK , Wong Martin CS , Tsoi Kelvin KF 
Published: February 2022

AbstractBackgroundDrawing is a major component of cognitive screening for dementia. It can be performed without language restriction. Drawing pictures under instructions and copying images are different screening approaches. The objective of this study was to compare the diagnostic performance between drawing under instructions and image copying for MCI and dementia screening.MethodA literature search was carried out in the OVID databases with keywords related to drawing for cognitive screening. Study quality and risk of bias were assessed by QUADAS‐2. The level of diagnostic accuracy across different drawing tests were pooled by bivariate analysis in a random effects model. Summary estimates of sensitivity and specificity with 95% CI and prediction region were presented in a hierarchical summary receiver operating characteristic (HSROC) curve. The area under the hierarchical summary receiver‐operating characteristic curve (AUC) was constructed to summarize the diagnostic performance.ResultNinety‐two studies with sample size of 22,085 were included. The pooled results for drawing under instructions showed a sensitivity of 79% (95% CI: 76 – 83%) and a specificity of 80% (95% CI: 77 – 83%) with AUC of 0.87 (95% CI: 0.83 – 0.89). The pooled results for image copying showed a sensitivity of 71% (95% CI: 62 – 79%) and a specificity of 83% (95% CI: 72 – 90%) with AUC of 0.83 (95% CI: 0.80 – 0.86) (Fig. 1). Subgroup analysis for the diagnostic accuracy for MCI and dementia showed that both drawing under instructions and image copying have better diagnostic performance for patients with dementia. The AUC of drawing under instructions and image copying for patients with dementia were 0.88 (95% CI: 0.85 – 0.91) and 0.85 (95% CI: 0.82 – 0.88) and the AUC for patients with MCI were 0.77 (0.73 – 0.80) and 0.73 (95% CI: 0.69 – 0.77), respectively. Most of the studies used clock‐drawing test as the screening test.ConclusionDrawing under instructions showed a similar diagnostic performance when compared with image copying for cognitive screening and the administration of image copying is relatively simpler. Self‐screening for dementia is feasible to be done at home in the near future.
Very high interrater reliability for manual segmentation of the medial perirhinal cortex
Authors: Henzen Nicolas A. , Reinhardt Julia , Blatow Maria , Kressig Reto W. , Krumm Sabine 
Published: February 2022

AbstractBackgroundIntracellular neurofibrillary tangles (NFT) belong to the main characteristics of Alzheimer’s disease (AD) pathology and occur first in the medial perirhinal cortex (mPRC; also referred to as “transentorhinal region”). Adjacent regions such as lateral perirhinal cortex (lPRC), entorhinal cortex (ERC), and hippocampus are affected at a later stage of NFT progression. Therefore, mPRC integrity potentially serves as a promising imaging biomarker in early AD. Due to the high anatomic variability of the collateral sulcus, which defines mPRC boundaries, it is important to evaluate the interrater reliability of manual segmentation. Today, automated segmentation protocols only exist for the whole PRC (i.e. mPRC and lPRC together). However, discrete analysis of mPRC integrity is crucial to detect AD related pathology as early as possible.MethodForty‐four adults (20 men; mean age = 69.2 ± 10.4 years) from different diagnostic groups (e.g. normal controls, mild cognitive impairment, Alzheimer's dementia or major depression) were included in the analyses. All subjects received structural magnetic resonance imaging in a 3‐Tesla scanner (MAGNETOM Verio, Siemens). Regions of interest (mPRC, lPRC, and ERC) were drawn by‐hand by two raters (SK, NAH) blinded for diagnoses. Bilateral cortical thickness estimates were extracted using FreeSurfer. Intraclass correlation coefficients (ICC) were calculated in SPSS based on a single‐rating, absolute‐agreement, 2‐way mixed‐effects model.ResultA high degree of reliability was found between both raters with an average measure ICC of .876 for the left mPRC (F[43,43]=14.954, p<.001, 95% confidence interval [CI] =.784 ‐ .930) and .873 for the right mPRC (F[43,43]=14.472, p<.001, 95% CI=.779 ‐ .929). Similar results were found for lPRC (left: ICC=.984; F[43,43]=118.834, p<.001, 95% CI=.970 ‐ .991; right: ICC=.953; F[43,43]=40.344, p<.001, 95% CI=.915 ‐ .974) and ERC (left: ICC=.969; F[43,43]=62.657, p<.001, 95% CI=.944 ‐ .983; right: ICC=.961; F[43,43]=49.390, p<.001, 95% CI=.930 ‐ .979).ConclusionThe ICC analysis showed a very high interrater reliability for manual mPRC segmentation as well as for lPRC and ERC. These results indicate that the applied segmentation protocol, which considers collateral sulcus variability, allows different raters to achieve highly similar results and may serve as a reference to establish future automated segmentation protocols.
Baseline CSF phosphorylated tau as an indicator of subsequent tau accumulation on tau PET
Authors: Cogswell Petrice M , Wiste Heather J. , Mielke Michelle M. , Schwarz Christopher G. , Weigand Stephen D , Lowe Val J , Therneau Terry M. , Knopman David S. , Graff‐Radford Jonathan , Vemuri Prashanthi , Senjem Matthew L. , Gunter Jeffrey L. , Petersen Ronald C. , Jack Clifford R. 
Published: February 2022

AbstractBackgroundAlzheimer’s disease biomarkers of tau pathology may be assessed by both CSF and PET. Cross‐sectional associations between CSF phosphorylated tau (p‐tau) and tau PET have been studied and regional tau PET SUVR has been shown to have similar diagnostic performance as CSF p‐tau. The association between CSF p‐tau and longitudinal tau PET has not been studied. CSF measures may be thought of as a result of the imbalance of influx vs efflux of soluble tau, whereas, tau PET reflects total tau accumulation into insoluble aggregates to date. We therefore hypothesize that baseline CSF p‐tau may be a leading indicator of future tau PET accumulation.MethodWe identified Mayo Clinic Study of Aging (MCSA) and Mayo Alzheimer’s Disease Research Center (ADRC) participants with diagnoses of cognitively unimpaired, mild cognitive impairment, and amnestic dementia who had CSF p‐tau (Elecsys p‐tau [181P]) and subsequent serial tau PET (flortaucipir) exams. The first tau PET scan was within 3 years of the CSF p‐tau collection. A longitudinal pipeline with two‐compartment partial volume correction was used to measure change in tau PET in a temporal‐lobe meta‐ROI (amygdala, fusiform, middle/inferior temporal, entorhinal, and parahippocampal regions) with a composite reference region (eroded supratentorial white matter, pons, and whole cerebellum). Spearman correlation was used to assess the association between CSF p‐tau and annual percent change in tau PET. A linear mixed effects model was fit to assess the association adjusting for age and sex.ResultThe study included 143 participants (76% cognitively unimpaired) (). CSF p‐tau was significantly associated with annual percent change in tau PET overall (Spearman R=0.19, p=0.023) () and after adjusting for age and sex (p<0.001) (). There was nonlinearity in the CSF p‐tau effect, with higher values (>20 pg/mL) having a greater association with annual change in tau PET than lower values.ConclusionIn a group of cognitively unimpaired and impaired participants, CSF p‐tau predicted subsequent tau PET accumulation rate. A threshold effect is suggested with subsequent tau PET accumulation primarily in participants with elevated CSF p‐tau levels near the Mayo threshold of 22 pg/mL.
Danish national film archives available for reminiscence activities
Authors: Jensen Anders Møller , Gregersen Rikke 
Published: February 2022

AbstractBackgroundAmong important elements’ in person‐centred care is knowledge about a person’s life, and how this ties into his/her daily activities and care. Finding historical film footage about a particular local setting, or a relevant topic, is time‐consuming and difficult for the care staff. The Danish Film Institute – a government institution under the Ministry of Culture – set out to develop a platform that made part of their historical archive available for staff, to support the national agenda of creating a dementia‐friendly society.MethodBased on knowledge from reminiscence theory, suitable archive footage was selected and grouped into four packages, consisting of several short film clips and supportive documents. The platform was tested on eight nursing home residents with a dementia diagnosed, in two groups of four. Each group performed one session per week for three weeks at the nursing home. Due to COVID‐19 restrictions, only proxy data was collected in terms of interviews with a group leader and two on‐site observers after every session, about their experiences with the material and their observed participant reactions. Data collection without the voices of the participants themselves was performed due to the need for obtaining at least proxy data on the effect of targeted film clip to stimulate frail elderlies with dementia – also in a pandemic lockdown situation. Informed consent from all participants was obtained. Data and ethics approval was done in accordance with Danish law.ResultsAlthough the archive content was not targeted people with declining cognitive function, the staff assessed the effect of this pedagogical dissemination of well‐designed film clip content, as very positive in relation to the participants with dementia. The sessions managed to stimulate engaging discussion and storytelling about the participant's own life in what can be described as deep memory recollections. Some instances of transference of new knowledge about life history to daily care of the participants were reported.ConclusionThe study instances that tailored archived film content can be used in professional person‐centred care to stimulate memories of people with dementia and quality moments in participant`s daily life.
Individualized MR‐based prediction of cognitive performance in subjects at risk of dementia
Authors: Nemali Aditya Sai Ram , Yakupov Renat , Schütze Hartmut , Spottke Annika , Ramirez Alfredo , Schneider Anja , Metzger Coraline D. , Christoph Laske , Bittner Daniel , Brosseron Frederic , Priller Josef , Wiltfang Jens , Buerger Katharina , Fließbach Klaus , Heneka Michael T. , Peters Oliver , Speck Oliver , Nestor Peter J. , Teipel Stefan J. , Pross Verena , Glanz Wenzel , Wagner Michael , Jessen Frank , Düzel Emrah , Ziegler Gabriel 
Published: February 2022

AbstractBackgroundNeuroimaging markers based on MRI often provide better prediction than traditional neuropsychological scores. With advancements of machine learning, data patterns may offer opportunities to personalize clinical practice that leads to better outcomes for patients at risk of dementia such as Alzheimer’s disease (AD) (Davatzikos et al., 2019). AD is a multifactorial process associated with ageing, brain atrophy, genes, proteins, vascular risk, and brain state activity (Frisoni et al., 2010). These processes do covary and interact in a complex fashion which needs to be accounted when aiming at predicting clinical outcomes for staging and stratification of disease‐modifying treatments.MethodIn our probabilistic predictive framework we focus on data from the DZNE DELCODE cohort (Jessen et al., 2018) consisting of T1‐weighted and FLAIR images to assess distributed patterns of Voxel‐based Morphometry (VBM) and White Matter Lesions for 929 subjects; subject‐specific demographics (age, sex, education) and available CSF biomarkers for 438 subjects. We developed a machine learning framework for brain‐based predictions of (A) memory performance (Wolfsgruber et al., 2020) and (B) CSF Amyloid 42/40 and p‐tau biomarker status using a Gaussian process multi‐kernel (GP‐MKL) learning approach (Rasmussen & Williams, 2006). The proposed GP‐MKL model combines multiple features (atrophy patterns, demographics age, sex, education, white matter lesions volume & apoe4) expected to characterize the transition from healthy ageing towards dementia in terms of cognitive symptoms and biomarker status (Figure 1). We evaluate predictive models and different feature combinations using 10‐fold cross‐validation.ResultThe framework enabled optimal individual prediction of memory performance (highest correlation true vs. predicted of r = 0.751 ± 0.082, R2 = 0.56, Fig. 2) using a combination of demographics, brain tissue segments (GM & CSF) & CSF biomarkers (Aß42/40 & p‐tau). When estimating the CSF biomarker positivity, the AUC‐ROC score achieved 0.735 for Aß42/40 (Fig. 4A) and 0.802 for p‐tau (Fig. 4B) using a combination of brain tissue segments (GM & CSF), demographics, and cognitive testing.ConclusionIn conclusion, multiple domains and imaging facets contribute to reliable estimation of individual cognitive memory performance and biomarker positivity in dementia and enable promising predictive technologies for staging and treatment stratification.