bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced diffusion‐weighted MRI methods demonstrate improved sensitivity to white matter aging: Percentile charts for over 15,000 UK Biobank participants
Authors: Lawrence Katherine E. , Nabulsi Leila , Santhalingam Vigneshwaran , Abaryan Zvart , Villalon‐Reina Julio E. , Nir Talia M. , Gari Iyad Ba , Zhu Alyssa H. , Haddad Elizabeth , Muir Alexandra M. , Laltoo Emily , John John P. , Venkatasubramanian Ganesan , Jahanshad Neda , Thompson Paul M. 
Published: February 2022

AbstractBackgroundAging and Alzheimer’s disease are both associated with alterations in the brain’s white matter. Understanding how the brain’s white matter changes as we age may also improve our understanding of processes involved in Alzheimer’s disease. Here we investigated the ability of both traditional and advanced diffusion‐weighted MRI methods to capture age effects on white matter microstructure in a large‐scale, population‐based sample of middle‐aged and older adults.MethodDiffusion‐weighted MRI (dMRI) scans were analyzed from 15,628 UK Biobank participants (age: 45‐80 years; 47.6% male). Diffusivity metrics were derived using four dMRI reconstruction models, including traditional diffusion tensor imaging (DTI) and the following advanced dMRI models: the tensor distribution function (TDF), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator MRI (MAPMRI). Metrics were projected to a standard white matter skeleton using publicly available ENIGMA protocols based on FSL’s tract‐based spatial statistics and the JHU atlas. Mean values for each dMRI metric were extracted from the whole white matter skeleton (full WM) and for the corpus callosum (CC). We investigated effects of age, sex, and their interaction on each dMRI metric for the full WM and the CC separately, to rank the sensitivity of these different metrics. Sex‐stratified centile reference curves were created for each dMRI metric to provide normative charts of white matter aging for this population.ResultParticipant age and sex were both significantly associated with full WM and CC microstructure for nearly all dMRI metrics, with TDF exhibiting the greatest sensitivity to age and NODDI the greatest sensitivity to participant sex (Figure 1). A significant age by sex interaction was observed in the full WM and the CC for many dMRI measures; NODDI detected this interaction with the greatest sensitivity. (Figure 1). Normative centile reference curves are presented for all dMRI indices separately for men and women (Figures 2 and 3).ConclusionParticipant age and sex robustly impact the brain’s white matter microstructure, with advanced dMRI models displaying the greatest sensitivity to such differences. These findings offer a normative reference to guide future studies and treatment of Alzheimer’s disease.
Cognitive function of the elderly without dementia in Korea: Cross‐sectional study
Authors: Bae Mi‐ae , Chang Kyung Ja 
Published: February 2022

AbstractBackgroundThe decline of cognitive function is common in the elderly. However, it should not be overlooked as it could be a risk factor for mild cognitive impairment or dementia in the future. The purpose of this study was to evaluate the cognitive function of the elderly without dementia in Korea.MethodsThe subjects were 274 elderly (78 males and 196 females) without dementia living in some areas of Korea. The cognitive function of the subjects was evaluated using the Mini‐Mental State Examination for Dementia Screening (MMSE‐DS), and compared by gender, age, educational period. In addition, the proportion of subjects below the criteria score based on demographic information of MMSE‐DS was evaluated, which indicates the possibility of developing mild cognitive impairment or dementia in the future. All data were collected through the face‐to‐face examination from 2015 to 2020, and statistical analysis was performed using SPSS 26.0.ResultsThe total MMSE‐DS score of subjects was good at 24.9 points, but scores of female elderly were significantly lower than those of male elderly in total score, place orientation, attention, and language (p<0.05). The scores of the elderly aged over 80 were significantly lower than those of the elderly aged 65‐69 and 70‐79 in total score, time orientation, place orientation, and language (p<0.001). The total score of the uneducated elderly was significantly lower than that of the elderly who graduated from elementary, middle, and high school (p<0.001). The proportions of subjects below the criteria score of MMSE‐DS were 16.4% in all subjects, 20.5% in male elderly, and 14.8% in female elderly. The proportions were 12.9 to 20.6% by age and by education period. The total MMSE‐DS score of the subjects was shown to be positive correlations with age and education period (p<0.001).ConclusionsThese results showed that cognitive function were lower in female elderly, the elderly aged over 80, and uneducated elderly, and proportions of the elderly with a high risk of dementia were 10 to 20% of the all subjects. Therefore, it is necessary to prepare measures such as regular mental health screening for early detection and preventive management of dementia in the elderly.
Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer’s continuum
Authors: Vilor‐Tejedor Natalia , Ciampa Iacopo , Operto Greg , Falcon Carles , Suarez‐Calvet Marc , Crous‐Bou Marta , Shekari Mahnaz , Arenaza‐Urquijo Eider M. , Milà‐Alomà Marta , Grau‐Rivera Oriol , Minguillón Carolina , Kollmorgen Gwendlyn , Suridjan Ivonne , Zetterberg Henrik , Blennow Kaj , Guigó Roderic , Molinuevo Jose , Gispert Juan Domingo ,   for the ALFA Study
Published: February 2022

AbstractBackgroundPerivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. However, the relationship between enlarged PVS (ePVS) and risk factors or pathophysiological mechanisms involved in Alzheimer’s disease (AD) remains unknown. The aim of this study was to investigate the association between the ePVS, demographic and cardiovascular risk factors, cognitive performance and CSF biomarkers of several pathophysiological mechanisms for AD.MethodThe study included 322 middle‐aged cognitively unimpaired participants from the ALFA+ study, many within the Alzheimer’s continuum. The exploratory Roche NeuroToolKit assays, a panel of automated robust prototype assays, and Elecsys® immunoassays were used to measure CSF Aβ42, Aβ40, p‐tau and t‐tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α‐synuclein. Cognitive performance was measured using a Preclinical Alzheimer Cognitive Composite (PACC) score. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4‐point visual rating scale [Figure 1]. Odds ratios were calculated for associations of cognitive performance, cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aβ status (positivity defined as Aβ42/40 < 0.071).ResultThe degree of PVS enlargement significantly increased with age in both BG and CS regions independently of cardiovascular risk factors. Higher levels of p‐tau, t‐tau, and neurogranin were significantly associated with ePVS in the CS of Aβ‐positive individuals, after accounting for relevant confounders [Figure 2], but no other significant associations were found.ConclusionOur results support that ePVS in the CS are associated with tau pathophysiology, and synaptic dysfunction in asymptomatic stages of the Alzheimer’s continuum.
Quality of life, mood and cognitive performance in older adults with cognitive impairment during the first wave of COVID 19 in Argentina
Authors: Aragón Irina , Flores Ignacio , Dorman Guido , Rojas Galeno , Sanjurjo Natalia Sierra , O'Neill Santiago 
Published: February 2022

AbstractBackgroundIn Argentina, government has established lock down on 19 March in order to decrease SARS‐COV 2 infection. These restrictions have remained effective for long time, with increase of anxiety depression and insomnia as shown in several studies. Older population was particularly at risk due to greater limitations to go out. Our objective was to evaluate the impact of confinement in quality of life, mood and cognitive performance of older adults with cognitive impairment.MethodLongitudinal descriptive‐observational study. Patients with cognitive impairment (CDR 0.5‐1) attending to virtual cognitive stimulation sessions have participated. Participants have completed by themselves Quality of Life in Alzheimer's Disease scale (QOL AD), Beck Depression Inventory (BDI‐II), Test your Memory (TYM) and an attention and executive battery created by our institution. Same assessments were done at the beginning of the lock down and 7 months later. SPSS program was used and means, standard deviations and paired‐samples t test were calculated.Result51 adults (43 women, mean age: 68.53 SD: 8.06, mean education: 14.33 SD: 2.63) were included. An increase in BDI ‐II score (p = 0.049) and worse performance in one of the executive attention tests (p = 0.012) were found. No significant differences in total score of QOL‐AD (p = 0.090), TYM (p = 0.067), verbal fluency (p = 0.323) or memory tests (p = 0.098) were found. Reviewing sub items, differences in changes in sleep habits (p = 0.021), decrease in the energy level (p = 0.004), worse subjective record of memory capacity (p = 0.028) and decrease in ability to do housework (p = 0.007) were found. In those who lived alone a higher score in BDI ‐ II (p = 0.030) and TYM (p = 0.22) were found.ConclusionThis is the first longitudinal study that measures the impact of lockdown on quality of life and cognitive performance in older adults with cognitive impairment in Argentina. Lockdown and isolation have shown worsening of mood and some quality of life variables and decrease in attention. Finally, our results show an increase in depressive symptoms in those patients who lived alone.
Brain structural changes in subjective cognitive decline: A whole brain surface‐based analysis in the FACEHBI cohort
Authors: Alonso‐Lana Silvia , Sotolongo‐Grau Oscar , Tartari Juan Pablo , Sanabria Angela , Alarcón‐Martín Emilio , Valero Sergi , Montrreal Laura , Orellana Adelina , de Rojas Itziar , Vivas Assumpta , Tejero Miguel Angel , Gómez‐Chiari M. , Perissinotti Andrés , Niñerola‐Baizán Aida , Ruiz Agustin , Tarraga Lluis , Marquié Marta , Boada Mercè ,   the FACEHBI Study Group
Published: February 2022

AbstractBackgroundSubjective cognitive decline (SCD) has been associated with increased risk of subsequent mild cognitive impairment (MCI) and dementia. Evidence from magnetic resonance imaging studies shows that neurodegenerative changes are already present years before dementia and thus, examining brain changes in SCD may contribute to identify potential biomarkers at an early stage of Alzheimer’s disease.Method198 individuals with SCD from the FACEHBI cohort were included (124 females; mean age 65.76 years). All subjects underwent magnetic resonance imaging and 18F‐Florbetaben positron emission tomography scan at baseline and were clinically follow‐up. Whole‐brain cortical surface‐based morphometry analysis were conducted using Freesurfer. Changes in cortical morphology (cortical thickness and surface area) were examined in relation to age, gender, brain amyloid beta deposition, ApoE‐e4 status (52 carrier/ 146 non carrier) and progression to MCI or dementia at the 4‐year follow‐up. Age, sex and years of education were included as covariates in all analyses.ResultAt p=0.05 corrected, higher age was associated with widespread cortical thickness reduction and reduced surface area in bilateral parahippocampal, left cuneus and middle frontal and in the right superior frontal cortex. Males had reduced cortical thickness in the right lingual and reduced surface area in the right superior temporal cortex. Higher amyloid beta deposition was related to higher surface area in the left inferior parietal cortex and no significant results were found in relation to ApoE‐e4 status. At the 4‐year follow‐up, 33 subjects had progressed to MCI and 118 remained cognitively unimpaired, but there were no significant differences in baseline cortical thickness or surface area between them. With a liberal threshold of p<0.0001 uncorrected, we found a cluster of reduced cortical thickness in the right isthmus cingulate in those who converted to MCI four years later.ConclusionBrain morphological changes in SCD are mainly characterized by cortical thickness reduction in relation to age and increased left inferior parietal surface area in relation to higher brain amyloid burden. Baseline reduced cortical thickness in the right isthmus cingulate is the only region associated with subsequent clinical progression to MCI and thus, it might be a useful predictive biomarker of cognitive decline in SCD individuals.
Effect of a home‐visit intervention on emotional well‐being for ethnic minority dementia family caregivers: Use of mindful breathing and compassionate listening
Authors: Lee Jung‐Ah , Gibbs Lisa 
Published: February 2022

AbstractBackgroundCaregiving burden and depressive symptoms among ethnic minority family caregivers with limited English proficiency (LEP) caring for persons with dementia (PWDs) in the United States negatively affect their health status and quality of life. The purpose of this study was to provide a home‐visit intervention that was culturally appropriate and language specific delivered by community health workers (CHWs) using mindful breathing and compassionate listening to these caregivers to reduce their burden, depressive symptoms, and negative affect (NA) and improve positive affect (PA).MethodsThe study design used a pre and post intervention by bilingual CHWs visiting participants’ home weekly for a month. CHWs demonstrated compassionate listening of the caregivers’ concerns and issues about caring for PWDs. In addition, CHWs taught the caregivers to practice mindful breathing several times a day as needed that has been shown to reduce anxiety. Burden, depressive symptoms, PA and NA were measured at baseline and after the 4‐week intervention. Wilcoxon signed‐rank tests were used to examine the difference in each outcome.ResultsTwenty‐five ethnic caregivers recruited from local community centers participated (8 Latino, 8 Korean, and 9 Vietnamese; 11 spouses and 14 offspring caregivers). All participants completed the intervention. The English proficiency of participants was 1.3/5 (SD=.91); 20% (5 of 25) reported they cannot speak English at all. Ethnic group differences on outcomes were not significant allowing for pooling of the data. Burden was significantly reduced (Mpre = 49.44 ±16.07, Mpost = 41.88 ±17.46, p=.008) and depressive symptoms decreased but were not significant (p=.091). The PA was significantly improved (Mpre=3.09±1.0, Mpost=3.60±1.0, p=.025) but not the NA (p=.090).ConclusionsThese findings show the potential to reduce caregiving burden and improve positive affect in ethnic minority dementia family caregivers receiving home visits by bilingual CHWs. Caregivers had the opportunity to express their concerns and issues freely to CHWs who demonstrated compassionate listening and taught them mindful breathing. Larger scale studies should be conducted to examine long‐term outcomes to improve ethnic minority dementia caregivers’ emotional well‐being.
Theta‐gamma phase‐amplitude coupling explains the advantage of auditory plus visual gamma entrainment in Alzheimer’s therapy
Authors: Fatemi Seyyedeh Nahaleh , Sedghizadeh Mohammad Javad , Aghajan Hamid 
Published: February 2022

AbstractBackgroundImpairment of gamma oscillations has been observed in cognitive disorders like Alzheimer’s disease (AD). Gamma entrainment using 40Hz auditory or visual stimulation has been proposed as a potential treatment for AD (Adaikkan et al., Trends in Neuroscience 2020; Sedghizadeh et al. Alzheimer’s and Dementia 2020), while simultaneous use of both modalities has been reported to show superior therapeutic results (Martorell et al., Cell 2019; Suk et al. Alzheimer’s and Dementia 2020). Gamma and theta oscillations are both produced in the hippocampal area and interact with each other. Evidence shows that the interaction between these bands leads to their phase‐amplitude coupling (PAC) in the frontal cortex (Amemiya et al., Cell Reports 2018). The current study assesses the effects of 40Hz auditory and visual stimulation on the theta‐gamma PAC, and suggests that the superior performance of multimodal entrainment can be explained by this marker.Method10 cognitively healthy participants were included in this study. Each participant was seated in a dark and quiet room and underwent three sessions of sensory stimulation (visual, auditory, and simultaneous (multimodal) visual and auditory) in a randomized order. Each session consisted of 60 trials of 5s stimulation and 5s rest. The auditory stimulation consisted of a 40Hz clicking sound modulated with a career frequency of 5kHz. The visual stimulation was generated using white LEDs flickering at 40Hz. EEG data were acquired and the theta‐gamma PAC was calculated using the time‐frequency mean vector length (tf‐MVL) method (Munia et al., Scientific Reports 2019).ResultThe PAC value for theta (4‐8Hz) and gamma oscillations near the stimulation frequency (39‐41Hz) on the Fz channel showed a significant increase during the multimodal stimulation intervals compared to the resting state, whereas the increase was not significant during the single‐modal stimulations compared to rest. The multimodal stimulation also involved more brain areas and resulted in a higher PAC compared to single‐modal stimulation.ConclusionEntraining gamma oscillations using simultaneous auditory and visual stimulation results in markedly superior theta‐gamma PAC compared to entrainment with single modalities. This superiority can explain the advantages reported for multimodal entrainment in AD therapy experiments.
Amyloid‐βeta peptides in CSF and plasma discriminate cerebral amyloid angiopathy from controls
Authors: Verbeek Marcel M. , de Kort Anna M. , Wermer Marieke J.H. , Marques Tainá M. , Kersten Iris , Schreuder Floris H.B.M. , Klijn Catharina J.M. , Stoops Erik , Brinkmalm Gunnar , Portelius Erik , Gkanatsiou Eleni , van Etten Ellis , Rasing Ingeborg 
Published: February 2022

AbstractBackgroundCerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid‐beta (Abeta) peptides in the cerebral vasculature and has been associated with vascular dementia and intracerebral haemorrhages (ICH). Currently, the diagnosis of CAA is based on neuroimaging and includes the identification of lobar (micro‐)bleeds and cortical superficial siderosis. However, these MRI markers reflect only late‐stage manifestations and are therefore not suitable for an early diagnosis of CAA. We aimed to evaluate the diagnostic potential of the Abeta peptides AB1‐38, AB1‐40, AB1‐42, and AB1‐43 in cerebrospinal fluid (CSF) to discriminate (early) CAA from controls.MethodWe used immunoassays to quantify AB1‐38, AB1‐40 and AB1‐42 in CSF and plasma and AB1‐43 only in CSF. CSF from sporadic CAA patients (n=28) and controls (n=40), and plasma from hereditary Dutch CAA (D‐CAA) patients (asymptomatic and symptomatic), sporadic CAA patients (n=129) and controls (n=99) were analyzed.ResultIn CSF we found decreased levels of AB1‐38 (p=0.03; AUC 0.64), AB1‐40 (p=0.04; AUC 0.63), AB1‐42 (p<0.0001, AUC 0.87) and AB1‐43 (p<0.0001, AUC 0.92) in CAA patients compared to controls. In plasma we found significantly decreased levels of AB1‐38, AB1‐40 and AB1‐42 both in asymptomatic and symptomatic D‐CAA mutation carriers compared to controls. The concentrations of all Abeta peptides strongly correlated with each other (Spearman r>0.6, p<0.0001 for each comparison).ConclusionAbeta peptides have strong biomarker potential for the diagnosis of (early)_CAA. Interestingly, our results indicate that AB1‐43, which has shown to be relatively low‐abundant in vascular amyloid deposits, has the highest diagnostic accuracy to discriminate CAA from controls. In addition, we show that CSF AB1‐38 levels are decreased in CAA compared to controls.
Using natural language processing to identify signs and symptoms of dementia and cognitive impairment in primary care electronic medical records (EMR)
Authors: Maclagan Laura C , Abdalla Mohamed , Harris Daniel A , Chen Branson , Candido Elisa , Swartz Richard H , Iaboni Andrea , Stukel Therese A , Jaakkimainen Liisa , Bronskill Susan E 
Published: February 2022

AbstractBackgroundFree‐text fields in electronic medical records (EMRs) are a rich source of information about persons with dementia. The signs and symptoms of dementia (e.g., responsive behaviours, cognitive impairment) can present to primary care providers many years before a formal diagnosis. We used natural language processing (NLP) to develop a list of features (i.e., dementia‐related key words) and compare classification algorithms to identify persons with dementia based on signs and symptoms documented in primary care EMRs.MethodWe used a validated algorithm based on administrative data to identify 526 persons with incident dementia (known positives) and 44,148 persons without (known negatives) aged 66+ from a primary care EMR database in Ontario, Canada between April 2010 and March 2018. A list of 900+ features associated with dementia was developed using literature review, clinician input and associated word embeddings. We trained a series of classification algorithms (e.g., gradient boosted models, neural networks, lasso and ridge regression) separately in progress notes and consult notes and compared their performance using nested 10‐fold cross validation.ResultPersons with dementia were older (mean:80.3 vs. 74.6 years) and more likely to have 5+ chronic conditions (11.6% vs. 7.8%). Persons with dementia had a median of 30.3 features per progress note (IQR:23.8, 40.4) and 54.7 per consult note (IQR:26.6, 83.8) compared to 27.5 (IQR:21.3, 36.5) and 32.1 (IQR:14.0, 55.6) for persons without dementia. Out of eight thematic groups (cognition, social, health system use, function, medication‐dementia, medication, symptoms, other), persons with dementia showed substantially more features related to cognition, social and medication‐dementia in progress and consult notes compared to persons without dementia. Using progress notes, the classification algorithm involving neural networks showed the best performance (Sensitivity:66.2%, Positive Predictive Value [PPV]:81.3%). Using consult notes, the gradient‐boosted classifier performed best (Sensitivity:45.4%, PPV:66.5%).ConclusionWe used NLP to discover informative features and develop classification algorithms to identify persons with dementia using free‐text EMR data. This could be used to improve recognition of early signs and symptoms of dementia by primary care providers to provide patients with appropriate interventions, including assessments, imaging and specialist referrals.