bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying individuals with non‐AD co‐pathologies: A precision medicine approach to clinical trials in sporadic AD
Authors: Tosun Duygu , Ellis Ryan , Weiner Mike W. , Yardibi Ozlem , Simen Arthur , Schwarz Adam J. 
Published: February 2022

AbstractBackgroundThe presence of co‐pathologies such as TDP‐43, Lewy bodies (LB), and cerebral amyloid angiopathy (CAA) is common in older individuals with AD, even those pathologically confirmed to have amyloid‐β and tau pathology, and contributes to cognitive and functional decline. Treatments targeting just one pathology will thus have variable and reduced overall measurable efficacy compared with an assumed population with no co‐pathologies. Tools to identify individuals with non‐AD co‐pathologies would be enabling technologies for a precision medicine approach to clinical trials in sporadic AD.In the absence of biomarkers to measure these co‐pathologies directly, our aim was to develop AI models to identify autopsy‐confirmed structural MRI‐based signatures of non‐AD degenerative brain pathologies, to facilitate participant selection for AD trials. This builds on the recent development of models to impute amyloid and tau positivity from structural MRI scans and associated clinical data.MethodADNI and NACC participants with ante‐mortem MRI and histopathologic assessments for scoring of neuritic plaques, staging of neurofibrillary tangles, LB, CAA, and TDP inclusions were included (Table 1). A multilabel classifier was trained on demographics, AD pathology, and MRI to jointly model positivity for TDP‐43, LB, and CAA. The leave‐one‐out validated model was applied to a separate ADNI cohort without neuropathologic assessments to assess the imputed prevalence of co‐pathologies at baseline and variance in cognitive decline and atrophy explained by baseline AD and non‐AD pathologies.ResultWhen optimized for 90% overall NPV (Fig. 1), the multi‐label classifier identified 16.0% of ADNI Dementia participants as TDP‐43+, 54.8% LB+, and 17.8% CAA+ (Fig. 2). While co‐pathology positivity was rare in cognitively unimpaired, LB and CAA positivity were common in MCI. Although dependent upon clinical disease stage, imputed probability of being TDP‐43+ explained a significant percentage of variance in clinical outcomes measures in cognitively impaired participants (Fig. 3).ConclusionThese initial results provide promising evidence that imputed co‐pathology burden via widely available imaging and clinical data can be used to impute the presence of non‐AD co‐pathologies and their contribution to cognitive decline in vivo. The primary limitation of this approach is the limited sample size in the autopsy cohorts for model development.
Automatic analysis and validation of digitized speech markers in Lewy body spectrum diseases with Alzheimer’s disease co‐pathology
Authors: Shellikeri Sanjana , Cho Sunghye , Liberman Mark Y. , Howard Erica , Balganorth Yvonne , Weintraub Daniel , Lee Eddie B. , Trojanowski John Q. , Irwin David J. , Grossman Murray , Nevler Naomi 
Published: February 2022

AbstractBackgroundLewy Body Spectrum Disorders (LBSD) are hallmarked by α‐synucleinopathy. Up to 50% of LBSD have co‐occurring Alzheimer’s Disease (AD) at autopsy and this is associated with earlier dementia onset, greater cognitive impairments, and reduced survival. In vivo identification of AD co‐pathology is currently achievable with invasive cerebrospinal fluid (CSF) AD biomarkers or costly molecular PET imaging. There remains a need for non‐invasive, inexpensive, and validated markers that can serve as screening tools for this purpose. We examined automated speech markers of a short semi‐structured natural speech sample in LBSD with and without neurobiologically‐validated AD co‐pathology.MethodWe analyzed digitized speech of Cookie Theft picture descriptions from 62 LBSD patients and 44 healthy controls (HC). AD co‐pathology was determined by neuropathological (25%) or CSF based diagnosis (75%): n=18 LBSD+AD (age= 73.7y (7.4), 67% Parkinson Disease (PD) /PD with Dementia (PDD), 33% Dementia with Lewy Bodies (DLB)); n=44 LBSD‐AD (age= 67.8y (6.5), 61% PD/PDD, 39% DLB). Speech samples were automatically parsed into voiced and silent segments and duration measures were extracted. Transcripts were processed for parts‐of‐speech usage and lexical‐semantic features. We conducted group comparisons of speech measures, examined their effects on determining pathologic group, and assessed relations with MRI cortical thickness.ResultLBSD+AD and LBSD‐AD groups did not differ in disease duration, motor disease severity (UPDRS Part III), nor neuropsychological performance (overall and across individual cognitive domains). Both LBSD+AD and LBSD‐AD spoke in shorter speech segments and longer and more frequent pauses; and speaking rate was slower compared to HC. Compared to LBSD‐AD, speakers with LBSD+AD used shorter words (by phoneme count) acquired at a younger age, and produced more conjunctions per 100 words. The features showed excellent model fit for determining pathologic group (McFadden R2 = 0.23), but speech features did not distinguish between PDD and DLB. Reduced word age of acquisition related to atrophy in left and right temporal regions in LBSD+AD only.ConclusionAutomated speech measures distinguished biologically‐confirmed LBSD+AD from LBSD‐AD regardless of clinical phenotype. Findings highlight the potential use of automated digitized speech analytics as a valid screening tool for AD co‐pathology in LBSD.
Accessibility of health care experienced by persons with dementia from ethnic minority groups and (in)formal caregivers: A scoping review
Authors: van Groenou Marjolein Broese , Duran Gozde , Van Hout Hein PJ 
Published: February 2022

AbstractBackgroundthe number of persons with dementia from ethnic minority backgrounds is increasing. However, ethnic minority groups use health care services less frequently compared to non‐migrants.MethodWe conducted a scoping review and used the theoretical framework developed by Levesque to provide an overview of the literature concerning access to health care for ethnic minority people with dementia and (in)formal caregivers. Our search strategy identified 28 empirical studies in the period 2008‐2019.ResultStudies mentioned barriers in (1) the ability to perceive a need for care in terms of health literacy, health beliefs and trust and expectations; (2) the ability to seek care because of personal and social values and the lack of knowledge regarding health care options; (3) lack of person‐centered care as barrier to continue with professional health care. Studies also mentioned barriers experienced by professionals in (1) communication with ethnic minorities and knowledge about available resources for professionals; (2) cultural and social factors influencing the professionals’ attitudes towards ethnic minorities; (3) the appropriateness of care and lacking competencies to work with people with dementia from ethnic minority groups and informal caregivers.ConclusionEthnic minority people with dementia and informal caregivers may benefit from improve their abilities to access health care. Health care professionals need to strengthen their competencies in order to facilitate access to health care for this group.
Regional cerebrovascular reactivity and cognitive performance among people with risk of cognitive decline
Authors: Kim Donghoon , Hughes Tim M. , Lipford Megan E. , Craft Suzanne , Baker Laura D. , Lockhart Samuel N. , Whitlow Christopher T. , Okonmah‐Obazee Stephanie , Hugenschmidt Christina E. , Bobinski Matthew , Jung Youngkyoo 
Published: February 2022

AbstractBackgroundCerebrovascular reactivity (CVR) is an indicator of the compensatory dilatory capacity of blood vessel in the brain in response to vasoactive stimuli. BOLD MRI‐measured CVR showed that CVR is correlated with cognition. However, BOLD signal is a complex combination of multiple parameters such as cerebral blood flow (CBF), cerebral blood volume, and oxygen metabolism. In this study, we directly measured CBF using dynamic arterial spin labeling (ASL) during a hypercapnia challenge and tested if regional CVR or CBF is related to cognitive performance among people with risk of cognitive decline.MethodSeventy‐eight subjects (age: 69±7.18 years, M/F: 22/56; BMI: 27.29±5.12; years of education: 15.6 ±2.45; 12 Type 2 diabetes with 6 under treatment; 38 hypertension; 23 under treatment or 14 both; MMSE score: 28.41±1.43) enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort underwent Pseudo‐continuous ASL during a 2‐minute baseline and a 2‐minute hypercapnic period with a RespirAct computer‐controlled gas blender, targeting 10mmHg higher end‐tidal CO2 level than the baseline while end‐tidal O2 level is maintained. Partial volume corrected voxel‐wise CVR was calculated (Figure 1). Multivariable linear regression analyses were performed to investigate the relationship between CBF or CVR and Mini‐Mental State Examination (MMSE) score in each ROI with adjustment for covariates: age, sex, race, BMI, years of education, hypertension/diabetic status, hypertension/diabetic medication status, and regional volume.ResultMultivariable linear regression analysis of CVR in the whole brain gray and white matter were positively associated with MMSE score (gray matter: =0.662, p=0.003, white matter: =0.474, p=0.027) (Figure 2‐a and b). Lower MMSE scores were significantly associated with lower CVR (corrected p<0.05) in 26 regions out of 122 gray matter ROIs (Figure 2‐c and 3). There was no significant relationship between regional white matter CVR and MMSE and between baseline CBF and MMSE score.ConclusionLower CVR in the whole brain gray and white matter and in the regional gray matter was related to lower MMSE score, while resting CBF showed no significant relationship with cognitive performance. Therefore, impaired CVR in the reported gray matter regions may be imaging biomarkers that predict cognitive performance.
Evaluation of an Arab American AD care intervention program in the United States
Authors: Ajrouch Kristine J , Janevic Mary , Alhamood Ammar J , Antonucci Toni C 
Published: February 2022

AbstractBackgroundThis initiative is part of a program of research designed to maximize the health and quality of life within the large Arab‐American community in Michigan through cultural/linguistic adaptations of the Alzheimer’s Association’s Living with Alzheimer’s education and support strategies program. Further, we aim to break new ground in terms of explicitly focusing on family systems as part of a caregiver support intervention.Methods10 families (two individuals from each, for a total of 20 individuals) signed up to attend the program. The program was offered twice virtually due to COVID‐19, delivered by bi‐lingual Arab American trainers. All participants were sent a link to an evaluation survey after completing the program (1=strongly disagree; 5=strongly agree) on: the usefulness of the program, the tip sheet, the language of delivery, and Alzheimer's Association resources. Descriptive analysis was conducted to ascertain rating frequency.ResultsSession 1 was delivered in English. Results showed that overall, all respondents agreed that the program was useful in that they learned something new and improved their caregiving skills. Half reported they neither agree/disagree about whether the program met their expectations with. Less than half reported they planned to use the Alzheimer’s Association resources available to them. Session 2 was delivered in Arabic. Results showed that overall, all respondents strongly agreed that the program was useful in that they learned something new and improved their caregiving skills. More than half strongly agreed the program met their expectations. More than half reported they planned to use the Alzheimer’s Association resources available to them. When asked “What would you change about this program” replies from both sessions asked to receive more strategies on how to deal with family members with Alzheimer’s. They also reported liking the Q&A time because that alleviated their feelings of the stigmatization of Alzheimer’s. As one said, “I felt at ease talking and sharing my experience with people who know what am I talking about.”ConclusionIdentifying successful and challenging elements of the adapted intervention will enable the creation of a program tool kit, which will set the stage for full‐scale broader implementation in underserved diverse populations.
Brain structural alterations in cognitively unimpaired individuals with discordant amyloid‐β PET and CSF Aβ42 status: Findings using machine learning
Authors: Cumplido‐Mayoral Irene , Shekari Mahnaz , Salvadó Gemma , Operto Greg , Cacciaglia Raffaele , Falcon Carles , Niñerola‐Baizán Aida , Perissinotti Andrés , Minguillón Carolina , Fauria Karine , Suridjan Ivonne , Kollmorgen Gwendlyn , Molinuevo Jose , Zetterberg Henrik , Blennow Kaj , Suarez‐Calvet Marc , Vilaplana Verónica , Gispert Juan Domingo ,   ALFA Study,   ADNI study
Published: February 2022

AbstractBackgroundCSF Aβ42 is thought to show AD‐related alterations earlier than amyloid‐β PET. Therefore, cognitively unimpaired (CU) individuals with abnormal CSF Aβ42 and normal amyloid‐β PET are believed to be in the earliest stages of the AD continuum. In this work, we sought to detect structural cerebral alterations in CU individuals with discordant status in these amyloid‐β biomarkers using Machine Learning techniques.MethodWe included 498 CU individuals from the ALFA+ and ADNI studies with available MRI, amyloid‐β PET and CSF Aβ42 measurements, the latter measured with the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays. In addition, we calculated Centiloid (CL) values for the PET measurements. Individuals were categorized as CSF‐/PET‐, CSF+/PET‐ and CSF+/PET+ according to established cut‐offs (CSF Aβ42<1098pg/mL for ALFA+ and <880pg/mL for ADNI, and CL<17 for PET). We trained XGBoost classifiers to predict amyloid‐β positivity using as features age, sex, APOE‐ɛ4 status, brain volumes and cortical thicknesses, obtained with Freesurfer 6.0 and the Desikan‐Kiliany atlas. Relevant features for pairwise‐group classification were sought (CSF‐/PET‐ vs CSF+/PET‐; CSF+/PET‐ vs CSF+/PET+; CSF‐/PET‐ vs CSF+/PET+), calculating SHAP values to determine the most important features for prediction.ResultWith respect the CSF‐/PET‐ group, the CSF+/PET‐ showed decreased gray matter volumes in the anterior and posterior cingulate/precuneus and increases in the lateral ventricles and bilateral parahippocampal gyri, among other regions (Figure 1A). Unexpectedly, the posterior cingulate/precuneus showed the opposite effect in cortical thickness measurements. These patterns were similar but more prominent in the comparison between the CSF‐/PET‐ vs CSF+/PET+ group (Figure 1B). Finally, CSF+/PET‐ group was characterized, with respect the CSF+/PET+ group by higher volume of the bilateral supramarginal gyri and lower cortical thickness in the posterior cingulate/precuneus (Figure 1C). Regarding the other variables in the model, APOE‐ɛ4 status was the most predictive variable in models with respect the CSF‐/PET‐ group and age in the CSF+/PET‐ vs CSF+/PET+ comparison.ConclusionOur results show that model‐free machine learning techniques can detect complex brain morphological alterations in the earliest stages of the AD continuum. Interestingly, some regions showed increases in volume and/or cortical thickness which may reflect compensatory or inflammatory effects.
Motor cerebro‐cerebellar network breakdown among different subtypes of Parkinson’s disease
Authors: Basaia Silvia , Agosta Federica , Francia Alessandro , Cividini Camilla , Stojkovic Tanja , Stankovic Iva , De Micco Rosita , Albano Luigi , Sarasso Elisabetta , Gardoni Andrea , Piramide Noemi , Markovic Vladana , Stefanova Elka , Kostic Vladimir S. , Filippi Massimo 
Published: February 2022

AbstractBackgroundTo investigate functional alterations in the cerebro‐cerebellar system in two Parkinson’s disease (PD) clinical phenotypes (tremor‐dominant [TD] and postural instability and gait disorder [PIGD]using stepwise functional connectivity (SFC).Method58 PD patients performed clinical and cognitive evaluations and resting‐state functional MRI (fMRI). PD cohort was divided into two groups: 32 patients with TD (PD‐TD) and 26 with PIGD (PD‐PIGD). 60 age‐ and sex‐matched healthy controls were also enrolled. SFC analysis aims to characterize regions that connect to specific seed brain areas at different levels of link‐step distances. The cerebellar seed‐region was identified using motor task‐based fMRI in 23 controls. For each of the SFC maps, whole‐brain two‐sample t‐test comparisons between groups were performed.ResultThe performance of the motor task during fMRI was associated with activation of the lobule VI and vermis of the cerebellum. SFC analysis at one‐link step distance showed, in both PD subtypes, a decreased regional–local connectivity between seed region and thalamus and parietal lobe relative to controls; across intermediate link‐steps, a reduced connectivity was observed with frontal, parietal and occipital lobes. Only PD‐PIGD patients showed lower connectivity at intermediate link‐step distances between the seed‐cerebellar region and sensorimotor areas. In addition, SFC pattern identified different localization of functional over‐connectivity in frontal lobe in both PD groups: in inferior frontal gyrus and insula in PD‐PIGD, and in orbitofrontal gyrus in PD‐TD.ConclusionThese findings highlight subtype‐specific PD changes in cerebellar functional connectivity, providing novel insights into the pathophysiological mechanism potentially underlying different motor phenotypes. Ministry of Education and Science Republic of Serbia (Grant #175090), Italian Ministry of Health (Grant #RF‐2018‐12366746).
Feasibility of the occupational therapy protocol TAP (Tailored Activity Program) for the management of behaviors in a dementia hospital unit: Preliminary results from a pilot study
Authors: Lanzoni Alessandro , Chiesa Roberto , Guerzoni Valentina , Romano Elisabetta , Tarozzi Adriano , Fabbo Andrea 
Published: February 2022

AbstractBackgroundBPSD may have a significant impact on the quality of life of people with dementia (PWD), cause significant burden in their caregivers (CG) and rise probability of hospitalization .The Tailored Activity Program (TAP) is an evidence‐based OT program based on meaningful activities of PWD. The primary goal of the program is to prevent and reduce BPSD. The intervention is delivered also toward professional and non professional CG to help them with the implementation of the identified strategies, delivered as tailored non‐pharmacological “prescriptions". OBJECTIVE: verify the applicability in Italy of the TAP OT program.MethodsThe program was adapted for the Italian cultural context in agreement with the main author. It consisted of 6 sessions to be carried out at the SCU‐B after being selected by the Geriatrician. Inclusion criteria for PWDs: MMSE <24, CDR <5, absence of psychiatric comorbidities.In addition to the applicability of the program, other parameters were also detected, specifically BPSD (UCLA‐NPI), autonomy (Barthel), quality of life (QUALID), the use of psychotropic drugs, the confidence of the CG in use of strategies.ResultsA total of 10 patients (age 80.7 ± 5.12) and their primary caregivers were recruited. The TAP program proved to be feasible in all its parts as required by the protocol within a specialist hospital dementia unit. There was also a reduction in BPSDs at NPI (median IN = 42; OUT = 12.5), an improvement in autonomy (Barthel median IN = 52.5; OUT = 57.5) and quality of life (Median QUALID IN = 31; OUT = 26). Caregivers reported greater confidence in using activities (M ± SD IN = 2.60 ± 1.96; OUT = 6.75 ± 2.31), communication (M ± SD IN = 4.40 ± 2.64; OUT = 7.63 ± 1.06) and environmental strategies (M ± DS IN = 3.30 ± 2.836; OUT = 7.25 ± 1.69) for the management of BPSDs at the end of the program.ConclusionsTAP was overall feasible and applicable in all its parts and has shown to be useful for both PWD and CG in different outcomes. It is necessary to enlarge the sample to confirm these preliminary positive results.
Inflammatory, degeneration and neuritic growth biomarkers predict cognitive decline and dementia in Parkinson’s disease
Authors: Hall Sara , Janelidze Shorena , Pereira Joana B. , Zetterberg Henrik , Blennow Kaj , Hansson Oskar 
Published: February 2022

AbstractBackgroundCognitive decline is common in Parkinson’s disease (PD) and has been associated with cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers such as Aβ1‐42, total tau and phosphorylated tau in addition to inflammatory proteins. VGF, a nerve growth factor, is a promising marker that has recently been implicated in cognitive decline in dementia with Lewy bodies and could potentially play a role in PD. The aim of this study is to assess a wide panel of CSF biomarkers reflecting different neuropathological processes to determine which best predict cognitive decline and conversion to dementia in PD.MethodWe included 174 PD patients from the Swedish BioFINDER study, who were followed for up to 10 years. At baseline, 47 CSF biomarkers were measured, including Aβ1‐42, Aβ42/40, total tau, phosphorylated tau, α‐synuclein as well as markers of neurodegeneration, vascular, inflammatory, synaptic and lysosomal dysfunction. Cox regression analyses were applied to identify biomarkers predicting dementia, adjusting for age, sex, education and disease duration. We then used linear mixed effects models to assess whether the significant biomarkers predicted longitudinal cognitive decline in MMSE, memory and semantic fluency, controlling for age, sex, education and disease duration.ResultOf the PD patients, 29% converted to dementia during follow‐up (4.9 ± 2.2 years). At baseline, converters were older (p<0.001) and had worse memory and semantic fluency tests (<0.008) compared with non‐converters. Levels of CSF Aβ1‐42, Aβ42/40, tau, Neurofilament light, Serum Amyloid A (SAA), Interleukin 7, Interferon‐gamma‐inducible Protein‐10 (IP‐10) and VGF (p<0.037) significantly predicted conversion to dementia in univariate models. When these biomarkers were included in a multivariable regression model, only higher tau (p<0.001), lower VFG (p<0.001) and higher SAA (p=0.028) independently predicted dementia. Further, CSF tau predicted cognitive decline in MMSE and semantic fluency (p<0.005), lower VGF predicted decline in memory (0.012) and SAA predicted decline in MMSE (p=0.011).ConclusionThese findings suggest that CSF tau, SAA and VGF are useful markers to predict conversion to dementia and cognitive decline in PD. VGF is emerging as an additional prognostic biomarker for cognitive decline in PD.