bluuebunny/crossref_metadata_2025_split huggingface dataset:
An app to measure functional decline in managing finances in Alzheimer’s disease: Preliminary results of the RADAR‐AD study
Authors: Stavropoulos Thanos G. , Mpaltadoros Lampros , Lazarou Ioulietta , Grammatikopoulou Margarita , Muurling Marijn , de Boer Casper , Curcic Jelena , Kouzak Rouba , Verheij Herman , Nies Vera J.M. , Durudas Andre , Hannesdottir Kristin , Hinds Chris , Daskalova Yoanna , Owens Andrew P. , Wu Yuhao , Erdemli Gul , Stolk Pieter , Lucivero Federica , Narayan Vaibhav A. , Aarsland Dag , Nikolopoulos Spiros , Tsolaki Magda , Visser Pieter Jelle , Kompatsiaris Ioannis 
Published: December 2021

AbstractBackgroundThe on‐going ‘Remote Assessment of Disease and Relapse – Alzheimer’s Disease’ (RADAR‐AD, https://www.radar‐ad.org/) international study uses remote monitoring technologies (RMT’s) to continuously and objectively monitor functional decline in Alzheimer’s Disease (AD). Managing finances is an Instrumental Activity of Daily Living (IADL), usually measured via traditional pen‐paper methods and interviews. To simulate this IADL, we present the ‘Banking App’ and preliminary results from the RADAR‐AD study.MethodIn the app, users enter a PIN, an amount to withdraw and confirm all inputs, using a numpad on a tablet’s touchscreen that resembles an ATM (Figure 1) provided in eight translations. Metrics collected include the duration and correctness of each step (i.e. PIN, Amount and confirmation) and attempt as a whole. The 36 participants to date (Figure 2), from four European sites, performed neuropsychological tests (e.g., MMSE, Rey) and include 20 amyloid negative cognitively normal healthy controls (HC) and 16 amyloid positive, of which 6 cognitively normal preclinical AD (PreAD), 6 cognitively impaired prodromal AD (ProAD) and 4 Mild to Moderate AD (MildAD). Clinicians provided a PIN and an amount to enter from a bill in a controlled lab setting. Statistical analysis included One Way ANOVA, t‐test and Mann‐Whitney between groups in pairs and Pearson correlation.ResultANOVA showed significance between groups mainly in amount and confirmation durations (p=0.010, p=0.002), leading to t‐test in group pairs (Figures 3 in numbers, visualized in Figure 4), showing increasing durations for more cognitively impaired groups and significant difference between amount and confirmation durations between HC and MildAD (p=0.011, p=0.002). Pearson correlations and heat map (Figure 5) relate app metrics and neuropsychological tests (e.g., MMSE, ADCS with correct amount, p=0.005, and confirmation duration, p=0.001).ConclusionPreliminary findings highlight that managing finances via an app relates to cognitive assessment, further supporting the potential of this IADL in early AD using technology. This promising early data including near‐significant trends (e.g., duration of tasks between PreAD and ProAD) will be investigated deeper as the study and data collection are on‐going. This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking RADAR‐AD (grant No 806999) and their associated partners.
Synergistic effects of CSF Aβ42 and p‐Tau on functional resting‐state connectivity in cognitively unimpaired individuals
Authors: Cacciaglia Raffaele , González‐de‐Echávarri José Maria , Milà‐Alomà Marta , Operto Greg , Falcon Carles , Minguillón Carolina , Fauria Karine , Suridjan Ivonne , Kollmorgen Gwendlyn , Molinuevo Jose , Zetterberg Henrik , Blennow Kaj , Suarez‐Calvet Marc , Gispert Juan Domingo ,   ALFA Study
Published: December 2021

AbstractBackgroundCerebral beta‐amyloid (Aβ) deposition disrupts functional resting‐state connectivity in cognitively unimpaired (CU) individuals. However, only a few studies have investigated these associations using Aβ cerebrospinal fluid (CSF) markers. Moreover, the reorganization of functional brain networks across the progressive stages of preclinical Alzheimer’s disease (AD) remains poorly understood. Here, we aim to identify functional connectivity (FC) differences in middle‐aged CU individuals, grouped as a function of both CSF Aβ (A) and pathological tau (T).MethodWe analyzed CSF and resting‐state functional magnetic resonance imaging (fMRI) data from 349 CU participants of the ALFA study (mean age=60.21 years). CSF Aβ42 and Aβ40 were assessed with the exploratory Roche NeuroToolKit robust prototype immunoassays, while p‐Tau181 was measured with the Elecsys® Phospho‐Tau (181P) CSF immunoassay (Roche Diagnostics International Ltd). Participants were grouped into three categories according to their biomarker status, resulting in three groups: A‐T‐, A+T‐, and A+T+. fMRI volumes were parceled into 218 regions, and correlations in the filtered fMRI signal among parcels were computed. We first assessed the impact of continuous CSFAβ42/40 concentration in the entire sample and subsequently assessed AT biomarker group differences in FC. A threshold of uncorrected p<0.005 using non‐parametric pair‐wise clustering was implemented.ResultA higher cerebral Aβ deposition, reflected by lower CSFAβ42/40, was associated with reduced FC within the default mode network (DMN), but increased FC between the visual network and the DMN, as well as the salience networks. Compared with A‐T‐, A+T‐ showed decreased within‐DMN connectivity (Fig. 1). Finally, compared with A+T‐, A+T+ individuals showed reduced FC within the temporo‐hippocampal (THN) and the executive control networks (ECN) (Fig. 2).ConclusionThis is the first study assessing FC in CU individuals adopting a staging of preclinical AD relying on multiple CSF biomarker classification. We report that CSFAβ42/40 disrupts the DMN but the co‐occurrence of Aβ and tau yields reduced connectivity in the THN and ECN, suggesting that Aβ and tau may interact in promoting a network reconfiguration extending beyond the DMN. Future studies shall clarify whether these differences reflect a correlate of pathology or rather a compensatory strategy to support cognitive performance in the face of AD pathology.
Interests of nursing homes residents with dementia for virtual reality‐based leisure activities: A cross‐sectional pilot study
Authors: Schüssler Sandra , Häussl Alfred , Paletta Lucas , Binder Thomas , Fürli Hermine , Koch Beatrix , Reidl Sybille , Beranek Sarah , Hartmann Robert , Sighart Martin , Schneeberger Michael , Andreu Jean‐Philippe 
Published: December 2021

AbstractBackgroundA lack of resources in nursing homes can lead to standardized (leisure) activities for residents because of insufficient tailoring of individual interests. Virtual reality (VR) has the potential to provide enjoyable leisure activities for positive outcomes like well‐being. This study explores past and possible future interests of nursing home residents with dementia for the development of VR‐based (leisure) activities.MethodThis cross‐sectional pilot study, a first step in a mixed‐methods project, used a standardized questionnaire based on the Modified Interest Checklist – Diverse Learners. In total, seven residents with mild dementia from one rural Austrian nursing home participated in the study in February 2020.ResultThe residents were mainly female (57%), on average 82 years old and partially care dependent. The most‐mentioned past interests were playing cards (85.7%) as well as swimming, cycling, singing, practicing arts and crafts, cooking and baking, gardening, and listening to music/the radio (71,4% each) followed by (family) visits, watching television, washing and ironing clothes with 57,1% each. Further reported interests were hiking, taking walks, dancing, and travelling/going on holidays with 42.9%. There was no interest (0%) in rowing, philosophy, playing computer games, Yoga, Zumba, American football, or baseball. Residents most‐mentioned possible future interests were singing, decorating rooms, listening to music/ the radio, and driving a car with 85.7%, followed by getting a massage, ninepin bowling, gardening, cooking and baking, watching TV, taking day trips, and reading with 71.4% each. Furthermore, 57.1% of the residents would enjoy doing some laundry and ironing, repair works, barbecues, and going walking or shopping. There was no interest (0%) in sports activities such as soccer, baseball, golf, or American football.ConclusionSurveying past and possible future interests of nursing home residents with dementia shows that especially the (leisure) activities gardening, listening to music/the radio, cooking and baking, washing and ironing clothes and taking walks are of high interest. This is the basis for the next step in the project, using qualitative interviews to obtain more detailed descriptions of residents’ explored interests to then develop VR‐scenarios for residents’ individual (leisure) activities needs.
Impact on ALFF and ReHO mapping of lifestyle multidomain intervention: The SUPERBRAIN study
Authors: Choi Seong Hye , Moon So Young , Shin Seong A. , Jeong Jee Hyang , Hong Chang Hyung , Park Yoo Kyoung , Na Hae Ri , Song Hong‐sun , Park Hee Kyung , Choi Muncheong , Lee Sun Min , Chun Buong‐O , Lee Jong‐Min 
Published: December 2021

AbstractBackgroundIn the South Korean study to prevent cognitive impairment and protect brain health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), we explored impact on amplitude of low‐frequency fluctuation (ALFF) and regional homogeneity (ReHo) mapping of 24‐week facility‐based multidomain intervention (FMI) and home‐based MI (HMI).MethodA total of 152 participants, aged 60‐79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the FMI, HMI, or control groups. Among them, 56 participants (20 FMI, 20 HMI, and 16 control) took brain MRIs at baseline and 24 weeks. We compared between each intervention and control groups in change of ALFF and ReHo mapping. The changes in ALFF and ReHo mapping were compared using analysis of covariance with age, sex, education, and scan centers as covariates. ROI‐based analysis was controlled for multiple comparisons with a false discovery rate threshold of P < 0.05.ResultOnly in the FMI group, a significant increase of ALFF in left medial orbitofrontal gyrus was observed after intervention. When 24‐week ALFF change in the left medial orbitofrontal gyrus was compared between each intervention and control groups, there was no difference. In HMI, increased ReHo was evident in right cuneus at follow‐up, whereas increased ReHo in left medial orbitofrontal gyrus and left anterior cingulate and decreased ReHo in right superior parietal lobule and right precuneus were observed in FMI group. The ReHo change in right cuneus was significantly higher in HMI group compared to the control group. The ReHo change in left medial orbitofrontal gyrus was notably higher in FMI compared to the control group. The correlation analysis revealed a positive correlation between the ReHo change in left medial orbitofrontal gyrus and change of serum brain‐derived neurotrophic factor (BDNF) levels in FMI group.ConclusionSignificant differences between the FMI and control groups on changes in ReHo in at‐risk elderly without substantial impairment in the SUPERBRAIN suggest that group preventive strategies at the facility may be beneficial on cognition through neuroplastic changes of functional processing circuits in the brain areas which play a crucial role in processing social information.
The heterogeneity of subjective cognitive decline: A data‐driven approach on a population‐based sample
Authors: Rolandi Elena , Ribaldi Federica , Vaccaro Roberta , Colombo Mauro , Frisoni Giovanni B , Guaita Antonio 
Published: December 2021

AbstractBackgroundSubjective Cognitive Decline (SCD) has been largely studied as a risk condition for cognitive decline, mainly in memory clinics or research settings. SCD samples are highly heterogeneous, including both individuals with early Alzheimer’s disease and others with psychological vulnerabilities and/or physical comorbidity. Aims: identify distinct SCD subgroups in a population‐based sample of cognitively normal (CN) older adults; explore cross‐sectional differences among SCD subgroups and controls (noSCD); investigate the effect of SCD status on 8‐year cognitive changes.MethodThe InveCe.Ab population‐based study (NCT01345110) enrolled people aged 70‐74 years residing in Abbiategrasso (Milan). Participants underwent multidimensional assessment (blood sampling, lifestyle interview, medical and neuropsychological assessment) at baseline (Nov 2009‐Jan 2011) and after 2, 4 and 8 years. CN participants at baseline completing at least 60% of neuropsychological assessment were included in the present investigation. Those reporting any cognitive complaints to the geriatrician were classified as SCD. Hierarchical cluster analysis was conducted in SCD including 9 relevant variables: education, depressive symptoms, cardiovascular risk, comorbidity, subjective cognitive complaints (numbers) and 4 neuropsychological scores measuring memory, executive functions, visuospatial abilities and language respectively. Cross‐sectional differences among the SCD subgroups identified and noSCD were performed using Kruskal‐Wallis test. Longitudinal cognitive changes according to baseline SCD status (noSCD, SCD subgroups) were estimated using linear mixed models, adjusted for age and education.ResultTwo clusters were identified in SCD. Table 1 shows cross‐sectional results. SCD1 (N=141), compared to SCD2 and CN, were less educated, have higher comorbidities, depressive symptoms and SCD complaints. SCD1 showed lower performances on executive and visuospatial functions, while SCD2, despite being healthier and more educated, showed reduced episodic memory. At longitudinal analysis, all cognitive functions declined due to aging (Time; p<.001). SCD2 displayed a steeper worsening on executive function (Group*Time; p<.001).ConclusionThe presence of SCD at the population level could be informative of future cognitive decline when reported by individuals with higher education. Future studies are needed to clarify the meaning of this condition in the aged population, in order to identify early those at increased risk of actual cognitive decline.
Early stages of tau pathology and its associations with functional connectivity, atrophy and memory
Authors: Berron David , Vogel Jacob W. , Insel Philip , Pereira Joana B. , Xie Long , Wisse Laura , Yushkevich Paul A. , Palmqvist Sebastian , Mattsson‐Carlgren Niklas , Stomrud Erik , Smith Ruben , Strandberg Olof , Hansson Oskar 
Published: December 2021

AbstractBackgroundIn Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau‐PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior‐medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance.MethodWe included 215 β‐amyloid negative cognitively unimpaired, 81 β‐amyloid positive cognitively unimpaired and 87 β‐amyloid positive individuals with mild cognitive impairment, who each underwent [18]F‐RO948 tau and [18]F‐flutemetamol amyloid PET imaging, structural T1‐MRI and memory assessments as part of the Swedish BioFINDER‐2 study.ResultFirst, event‐based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions (see Figure 1). Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau‐related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior‐medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy.ConclusionIn summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease‐stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe‐cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.
Impact of clinical symptoms and diagnosis: The electronic Person‐Specific Outcome Measure (ePSOM) development programme
Authors: Saunders Stina , Muñiz‐Terrera Graciela , Sheehan Shane , Luz Saturnino , Ritchie Craig W. 
Published: December 2021

AbstractBackgroundRegulatory bodies recommend that outcome measures used in Alzheimer’s disease (AD) clinical trials capture clinically meaningful changes for the trial participant. However, commonly used cognitive outcomes are limited in this regard. The aim of the electronic Person‐Specific Outcome Measure (ePSOM) programme is to better understand what outcomes matter to patients in early Alzheimer’s disease.MethodAs part of the ePSOM programme, we designed and ran an online study to understand what matters to individuals when developing new treatments for AD. The ePSOM survey ran Aug 2019 – Dec 2019 (UK) and collected primarily free text responses which were analysed using Natural Language Processing (NLP) techniques. Here, we focus on the responses from individuals diagnosed with Mild Cognitive Impairment (MCI); Alzheimer’s dementia or Other dementias. We compared each of these groups to the ‘no‐diagnosis’ group by undertaking chi‐squared tests for key demographic variables. Differences between the target and no‐diagnosis groups were looked for.ResultThe survey was completed by 5808 respondents, of whom 167 (2.9%) (women n=91, men n=69, other n=7) had received one of our three target diagnoses: [1] MCI n=61, 1.1% (mean age 69.42, SD=10.8); [2] Alzheimer’s Dementia n=57, 1.0% (mean age 71.24, SD=9.79; and [3] Other dementia n=49, 0.8% (mean age 69.67, SD=9.00). Respondents in the Alzheimer’s and Other dementia group were more likely to have lower educational level, whereas this effect was not found in the MCI group. Several thematic clusters were significantly more important for the target diagnostic groups in comparison with respondents who did not have a target diagnosis, e.g.,: “Expressing opinions” for the MCI group; “Playing Golf” for the Alzheimer’s dementia group; and “Maintaining Personal traits and social skills” for the Other dementia group.ConclusionThe results of the ePSOM survey focusing on the individual’s views with a MCI or Dementia diagnosis provide evidence for what these groups consider important when developing treatments for AD. The numerous clusters which were significantly more likely to be important for those with a particular diagnosis indicate that priorities shift along the preclinical, prodromal and overt dementia continuum. This has important implications for the development of outcome measures.
Relationship between cortical neural synchronization at alpha resting‐state electroencephalographic rhythms and education attainment in normal elderly subjects and patients with amnestic mild cognitive impairment due to Alzheimer’s disease
Authors: Noce Giuseppe , Babiloni Claudio , Ferri Raffaele , Lizio Roberta , Lopez Susanna , Lorenzo Ivan , Tucci Federico , Soricelli Andrea , Nobili Flavio Mariano , Arnaldi Dario , Famà Francesco , Giubilei Franco , Marizzoni Moira , Güntekin Bahar , Yener Gorsev , Stocchi Fabrizio , Frisoni Giovanni , Percio Claudio Del 
Published: December 2021

AbstractBackgroundIn normal old (Nold) and Alzheimer’s disease (AD) persons, a high cognitive reserve makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI).MethodData in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu‐) educational attainment subgroups, were available in an Italian‐Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware.ResultAs compared to the Nold‐Edu‐ subgroup, the Nold‐Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI‐Edu‐ subgroup, the ADMCI‐Edu+ subgroup displayed lower alpha source activations topographically widespread (Figure 1). Furthermore, the two ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray‐white matter measures, and neuropsychological scores.ConclusionThe current findings suggest that a high cognitive reserve may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.