bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability of Magnetoencephalography and Electroencephalography Spectral Features in Mild Cognitive Impairment
Authors: Kinnunen Antti S , Kulashekhar Shrikanth , Saarinen Timo , Mäntynen Ville , Hotta Jaakko , Koivisto Anne M , Liljeström Mia , Renvall Hanna , Consortium AI‐Mind 
Published: December 2023

AbstractBackgroundIn mild cognitive impairment (MCI), the first neurodegenerative changes may occur years before they can be effectively detected with current clinical tools. Early pathology has been linked to synaptic dysfunction causing brain network disturbances that may be observed with electroencephalography (EEG) and magnetoencephalography (MEG). These methods are still not widely utilized in dementia risk assessment, and the stability of suggested EEG and MEG features and their correlation has not been thoroughly addressed in this patient group.MethodIn a 5‐year EU Horizon2020 project ‘AI‐Mind’, we collect EEG and simultaneous MEG data from MCI subjects, to be compiled with cognitive, genetic and plasma biomarker measures and techniques based on artificial intelligence (AI) for predicting the overall dementia risk.Here, we analyzed a subset of 31 Finnish MCI participants (20 females, age 68 ± 5; mean ± SD) from the AI‐Mind dataset to assess the stability of prominent signal features from resting‐state EEG and MEG recordings. We determined within‐session test‐retest reliability for spectral peak frequencies and relative peak power over occipital brain regions in the 8‐13 Hz range, by utilizing intraclass correlation (ICC) for subsequent 5‐min runs of EEG and MEG data in both eyes‐closed (EC) and eyes‐open (EO) conditions. In addition, we determined the consistency of the features across methods (EEG/MEG).ResultThe results indicate good (ICC>0.6) test‐retest reliability across runs for EEG (peak frequency: 0.72 (EC); relative power: 0.86 (EC) and 0.66 (EO); p<0.001) and excellent test‐retest reliability (ICC>0.75) for MEG (peak frequency: 0.83 (EC); relative power: 0.96 (EC) and 0.85 (EO); p<0.001). Consistency across EEG and MEG was excellent (peak frequency: 0.86 (EC); relative power 0.89 (EC) and 0.84 (EO); p<0.001).ConclusionElectrophysiological recordings of brain networks are emerging as a diagnostic tool for early detection of dementia. Good stability of the measured signal features is a prerequisite for a clinically feasible tool. Here, we demonstrate good or excellent stability for prominent spectral features both within and across EEG and MEG recordings.
Modeling pathological spread through the structural connectome in the FTLD spectrum
Authors: Agosta Federica , Basaia Silvia , Facente Federica , Cividini Camilla , Spinelli Edoardo Gioele , Canu Elisa , Castelnovo Veronica , Ghirelli Alma , Magnani Giuseppe , Caso Francesca , Riva Nilo , Caroppo Paola , Prioni Sara , Villa Cristina , Tremolizzo Lucio , Appollonio Ildebrando , Verde Federico , Silani Vincenzo , Filippi Massimo 
Published: December 2023

AbstractBackgroundTo explore the relationship between network vulnerability and longitudinal atrophy progression in FTLD spectrum, using Network Diffusion Model (NDM) of pathology spread.MethodThirty‐four behavioural‐variant frontotemporal dementia (bvFTD), 11 semantic‐variant primary progressive aphasia (svPPA) and 11 nonfluent/agrammatic‐variant primary progressive aphasia (nfvPPA) patients underwent longitudinal T1‐weighted MRI. Forty‐eight young controls underwent multi‐shell diffusion MRI scan. NDM was developed to assess the progression of FTLD pathology originating from a seed (right orbitofrontal cortex [bvFTD], left inferior temporal gyrus [svPPA], and left supplementary motor area [nfvPPA]) and proceeding through the healthy connectome. The connectivity measures were fractional anisotropy (FA) and intra‐cellular volume fraction (ICVF). Correlations were tested between atrophy estimated by NDM and those empirically obtained in FTLD patients over a follow‐up of 24 months.ResultIn bvFTD, NDM showed an early spread to frontal lobe and basal‐ganglia and to right sensorimotor, parietal, temporal and occipital lobes, with a subsequent involvement of the left hemisphere. In svPPA, NDM suggested an early spread of pathology to the left occipital and frontal lobes, while parietal lobe was reached later. In nfvPPA, NDM‐predicted spread through all brain regions, except for occipital lobe. NDM‐predicted atrophy of each region was positively correlated to longitudinal atrophy empirically observed in all three FTLD variants. Overall, NDM with ICVF connectome provided higher correlation values relative to NDM with FA maps.ConclusionThe NDM implementation to cross‐sectional structural connectome is a valuable tool to predict atrophy patterns and pathology spreading in FTLD variants.Supported‐by: European‐Research‐Council (StG‐2016_714388_NeuroTRACK); Foundation Research on Alzheimer’s Disease.
The evolving role of intraneuronal amyloid‐β in Alzheimer’s disease
Authors: Gouras Gunnar K ,   Experimental Dementia Research Unit, Lund University
Published: December 2023

AbstractBackgroundIn 1998 at the Alzheimer’s Association conference in Amsterdam, I first presented on the accumulation of Alzheimer’s disease (AD)‐linked amyloid‐β42 (Aβ42) in cultured neurons and human brains with early AD pathology (later published in Gouras GK et al., 2000). Despite much skepticism, this early work led to a revision of the role of Aβ in AD that for the past 2.5 decades has been at the center of our group’s attempt to better define the earliest cellular stages of AD. Our current scenario, including with new data, will be presented for the role of intraneuronal Aβ in the early endosomal and synaptic alterations that initiate the disease process.MethodAD transgenic (overexpression and knock‐in) mouse models at different ages and postmortem human brains are analyzed using amongst others, microscopy and biochemical approaches for APP metabolites, and other AD‐linked, endosome and synapse proteins, with a focus on the earliest detectable alterations within AD vulnerable neurons. Brain injections of prion‐like Aβ and tract tracing methods are used to model early anatomical and cellular progression of pathology. Further, primary brain cultures from AD mice are used to model early AD cellular alterations.ResultPrior to classical amyloid plaques, smaller accumulations of Aβ develop within the endosome‐lysosome system of AD vulnerable neurons, with preferential aggregation near axonal and dendritic synaptic terminals with AD pathogenesis. Ongoing work is centered on elucidating the early alterations of different pools of APP metabolites, ApoE and Tau in the early biological pathways that impact synapses.ConclusionOur understanding of the early cellular dysfunction and pathology has evolved significantly over the past few decades, with a better appreciation for the importance of other cell types (e.g. astrocytes, microglia) and factors in AD, and recent, albeit modest, success in therapy targeting Aβ. We see aging, along with genes and lifestyle, as promoting the earliest Aβ‐related dysfunction in endosomal biology at synapses and are working to piece together the links between key AD‐related proteins in the disease process.
Comparing two picture naming tasks in Primary Progressive Aphasia: insights from behavioural and neural results
Authors: Conca Francesca , Polito Cristina , Santi Gaia Chiara , Esposito Valentina , Caminiti Silvia P , Boccalini Cecilia , Berti Valentina , Morinelli Carmen , Mazzeo Salvatore , Marcone Alessandra , Iannaccone Sandro , Bessi Valentina , Sorbi Sandro , Perani Daniela , Cappa Stefano F , Catricalà Eleonora 
Published: December 2023

AbstractBackgroundPicture naming tests are widely used to evaluate language impairments, especially in Primary Progressive Aphasia (PPA). The available instruments differ for type of stimuli and their psycholinguistic properties, known to affect the performance. We aim to identify the most appropriate naming test to be used on PPA, based on clinical and research demands.MethodWe investigated the behavioural characteristics (proportion of correct responses, error type) and the neural correlates of CaGi (Catricalà et al., 2013) and SAND (Catricalà et al., 2017) naming tests, administered to 84 healthy controls and 52 PPA (15 semantic, svPPA; 20 logopenic, lv‐PPA; 7 non fluent, nfv‐PPA; 10 mixed PPA), the latter also undergoing an FDG‐PET scan. We analyzed the ability of the tests in distinguishing PPA versus controls and between PPA variants, considering the psycholinguistic variables affecting the performance. We explored the brain metabolic correlates of the behavioural performance.ResultSAND, differently from CaGi, had response time limit and less frequent and later acquired items. A greater difficulty to name SAND items compared to CaGi ones was found. While semantic errors predominated in CaGi, both anomic and semantic errors were equally frequent in SAND. Both tests distinguished PPA from controls, but SAND outperformed CaGi in discriminating among PPA variants. FDG‐PET imaging revealed a shared metabolic involvement of the temporal areas, including the anterior fusiform gyrus, the temporal pole, and extending to the posterior fusiform gyrus in sv‐PPA, associated with lexico‐semantic processing.ConclusionA naming test with response time limits and more difficult items (as SAND) better highlights subtle distinctions between PPA variants, improving the diagnosis. Conversely, a naming test devoid of response time limits (as CaGi), may be more suited for an in‐depth characterization of the impairment and for guiding rehabilitation.
Neuropsychiatric symptoms and risk of cognitive impairment: Mayo Clinic Study of Aging
Authors: Syrjanen Jeremy A. , Krell‐Roesch Janina , Kremers Walter K. , Fields Julie A. , Scharf Eugene L. , Knopman David S. , Petersen Ronald C. , Vassilaki Maria , Geda Yonas E. 
Published: December 2023

AbstractBackgroundMost studies on the relationship between neuropsychiatric symptoms (NPS) and cognitive decline focus on NPS data collected over a short period of time. To better understand the association between NPS and cognitive decline, including their temporal relationship, it is important to know NPS status across a person’s life.MethodWe utilized the unique Rochester Epidemiology Project medical record linkage system that has captured medical records as far back as 1907, to abstract the psychiatric history of 1810 cognitively unimpaired participants in the population‐based Mayo Clinic Study of Aging (MCSA). Trained nurse abstractors ascertained the presence of exposure to three common NPS (anxiety, depression, and unspecified emotional distress [UED]), both before and after entry into the MCSA. We conducted Cox Proportional Hazards (PH) models using age as the time scale and adjusting for sex, education, and APOE E4 allele for each NPS in predicting mild cognitive impairment (MCI), or dementia. Additional analyses considering medication use (yes/no) and timing of NPS were also run.ResultAnxiety (Hazard Ratio [HR] = 1.47, p<0.001), depression (HR = 1.36, p = 0.001), and UED (HR = 1.22, p = 0.039) were associated with a higher risk of MCI. These associations were present regardless of medication use for anxiety (With medication: HR = 1.51, p<0.001; without medication: HR = 1.41, p = 0.015), and for those taking medications for depression (With medication: HR = 1.47, p<0.001; without medication: 1.09, p = 0.597). Anxiety was associated with MCI regardless of timing of onset with the strongest relationship being for those with onset of anxiety before 65 that persisted into later life (HR = 1.88, p = 0.004). Depression was associated regardless of timing of onset if the depression was present in late life too. The results were similar for the outcome of dementia (Anxiety: HR = 1.62, p<0.001; depression: HR = 1.31, p = 0.040; UED: HR = 1.37, p = 0.014). The associations accounting for medication use and timing of NPS were similar for the outcome of dementia too.ConclusionNPS is associated with progression to MCI and dementia. Both medication use and timing of NPS might play a role in these associations.
Plasma glial fibrillary acidic protein is associated with concomitant brain β‐amyloid in Lewy body disease
Authors: Cousins Katheryn A Q , Irwin David J. , Chen‐Plotkin Alice , Shaw Leslie M. , Arezoumandan Sanaz , Lee Eddie B , Wolk David A. , Weintraub Daniel , Spindler Meredith , Deik Andres , Grossman Murray , Tropea Thomas F. 
Published: December 2023

AbstractBackgroundWhile α‐synuclein (αSyn) is the primary pathology associated with Lewy body spectrum disorders (LBSD), concomitant Alzheimer’s disease (AD) pathology is common and is predictive of clinical outcomes, including worse cognitive impairment and shorter survival. Thus, AD plasma biomarkers may help identify clinically relevant co‐pathology in LBSD to improve prognosis and clinical management. Plasma phosphorylated tau 181 (p‐tau181) and glial fibrillary acidic protein (GFAP) are two biomarkers that have been well‐studied in canonical AD, showing reliable increases with AD neuropathological change (ADNC). However, their utility in autopsy‐confirmed LBSD is relatively untested.MethodIn autopsy‐confirmed LBSD with a neuropathological diagnosis of αSyn, we tested how plasma p‐tau181 and GFAP differed across αSyn with concomitant ADNC (αSyn+AD; n = 19) and αSyn without AD (αSyn; n = 30). αSyn+AD was defined by intermediate/high ADNC and αSyn had no/low ADNC; cognitively normal controls and AD without αSyn were included as reference groups (Table 1). Severity of burden was scored on a semi‐quantitative scale for β‐amyloid and tau, and scores were averaged across sampled brainstem, limbic, and neocortical regions. Plasma analytes were log‐transformed in linear models, and models covaried for plasma‐to‐death, age at plasma, and sex. Receiver operating characteristic (ROC) analyses and area under the curve (AUC) tested diagnostic utility of plasma analytes.ResultPlasma GFAP was significantly higher in αSyn+AD compared to αSyn (Figure 1), confirmed by linear models (β = 0.31, 95%CI = 0.065 – 0.56, p = 0.015); plasma p‐tau181 was not (p = 0.37). Next, linear models tested associations of AD pathological hallmarks with both plasma analytes. GFAP was significantly associated with brain β‐amyloid (β = 15, 95%CI = 6.1 – 25, p = 0.0018) and tau burden (β = 12, 95%CI = 2.5 – 22, p = 0.015); in the same model plasma p‐tau181 was not associated with either (both p>0.34). ROC analyses showed that neither analyte had an AUC>0.80 (Figure 2); GFAP had somewhat higher AUC of ADNC in LBSD (0.71; 90%CI = 0.58 – 0.83) than plasma p‐tau181 (AUC = 0.64; 90%CI = 0.50 – 0.77).ConclusionResults demonstrate elevated plasma GFAP in LBSD with concomitant AD pathology, in association with accumulation of β‐amyloid plaques. Findings highlight the importance of validating utility of AD biomarkers in LBSD, and the need for plasma biomarker strategies to detect concomitant AD in LBSD.
Availability and quality of facilities for people with dementia and their caregivers in Lithuania
Authors: Vaičekauskytė Živilė , Pšemeneckienė Greta , Petkutė Ieva , Karpavičiūtė Simona , Macijauskienė Jūratė 
Published: December 2023

AbstractBackgroundThe aim of this study was to evaluate the availability and quality of health care and social care services as well as information with dementia related topics for people with dementia (PWD) and their caregivers. The research project was a part of a project “Towards a Dementia Strategy: Situation Analysis and Public Awareness” financed by the EEA Grants 2014 – 2021 through the Active Citizens Fund.MethodThe questionnaire based on the literature and relevant themes for the county was developed with 65 questions for caregivers. An online anonymous survey was conducted from 2022 September to 2023 and distributed using “snowball” method, in which 68 respondents (mean 51.6 years of age) participated.Result48,5% of respondents cared for PWD in the early stage of disease up to five years. The mean duration to final diagnosis was 13.3 months. The most important criterion for caregivers during establishment of dementia diagnosis was conveyance about progression of disease (77.9%) and competency of health care specialists recognizing dementia symptoms (76.5%). Availability and quality of information during diagnosis establishment was evaluated 5.4 points (out of 10) and was dependent on specialist’s ability to communicate and clearly present information. 51.5% of respondents noted deficiency of information on dementia. 35.3% of respondents stated that health care services are fully provided and 23.5% of participants noted the deficiency of health care facilities, mostly services at home and outpatient rehabilitation services. Availability and quality of health care was evaluated 4.97 points (out of 10.) The most common social service is day social care service at person’s home (22.4%). 53.7% of participants noted that they do not use any social care services. Availability and quality of social care was evaluated 5 points (out of 10).ConclusionAvailability and quality of health care and social facilities for people with dementia are not meeting expectations of caregivers. There is a lack of information for people with dementia and their caregivers about dementia related topics. The scope of the study is insufficient for more detailed conclusions and further investigation is needed to induce the necessary changes.
The relationship between divorced status and in vivo beta‐amyloid pathology in cognitively normal older adults
Authors: Anjum Rifah , Chandra Avinash , Bothongo Phazha LK , Waters Sheena , Uchegbu Ijeoma , Jeraldo Rosario Isabel Espinoza , Byford Michelle , Marshall Charles R 
Published: December 2023

AbstractBackgroundSpousal loss or separation are stressful life events that have previously been linked to cognitive impairment in mid‐life and an increased risk of developing dementia in later life. Beta‐amyloid (Aβ) neuritic plaques are one of the neuropathological hallmarks of Alzheimer’s disease (AD) and it is thought that Aβ pathology may be one of the primary drivers of AD onset. Impacts of marital divorce on brain Aβ burden remains an underexplored area of research with initial work showing no association. However, this did not consider effects when subjects are grouped based on characteristics relevant to dementia risk. The objective of the current study was to examine associations between being divorced and Aβ positivity status in cognitively normal (CN) older subjects, and to determine differential effects when stratifying subjects by demographic or AD risk categories.MethodWe used data from 185 married or divorced CN older subjects who had a [18F]Florbetapir PET scan from Alzheimer’s Disease Neuroimaging Initiative at their baseline study visit. Subjects were further classified into Aβ positive or negative categories based on a global standardised uptake value ratio of greater than 1.11. Statistical analysis utilised multivariable logistic regression to examine associations between marital status and Aβ positivity, which controlled for age, gender, education, and MMSE score in the overall sample. This analysis was repeated in subgroups based on APOE ε4 status, age, education, and gender.ResultWhole‐group regression demonstrated no association between divorced (relative to married) status and Aβ burden in CN subjects (p = 0.389). Regressions run in subgroups showed significant associations between divorce and an elevated risk of Aβ positivity status specifically in groups of CN subjects who were either APOE ε4 allele carriers (p = 0.040) or in the youngest age tertile (55.8 – 69.3 years old) (p = 0.038).ConclusionResults from the current study highlight that brain Aβ burden on amyloid PET is positively related to the experience of divorce in older adults below 70 years of age or at elevated genetic risk for late‐onset AD. These findings might suggest that stress associated with divorce may exacerbate neuropathology typically seen in AD.
Quantitative text analysis of language use in rare dementia support groups
Authors: Hayes Oliver S , Baou Celine El , Hardy Chris JD , Brotherhood Emilie V , Harding Emma , Crutch Sebastian J 
Published: December 2023

AbstractBackgroundQuantitative text analysis facilitates study of internal states of speakers in an interspace between self‐report measures and qualitative analyses. The methodology is well‐established in psychological research, including in numerous support group settings.MethodIn this study, Linguistic Inquiry and Word Count (LIWC2015) was employed to characterise conversations in online multi‐component (peers and professionals) support groups for familial caregivers of people living with young onset, atypical or inherited (rare) dementias. Using a corpus of transcripts (129,616 words) from 14 sessions, the differences between trained facilitators’ (n = 2) and participants’ (n = 14) speech were examined, and the impact of agenda on discussion was investigated. Sessions were semi‐structured, addressing independence and identity, or unstructured, without agenda. Statistical methods included comparison of linguistic features with natural speech, Poisson regression, and a clustering algorithm.ResultMeaningful differences between natural speech and the corpus emerged, including in emotional tone (Tone; d = ‐3.2, p<0.001), level of analytic/informal language (Analytic; d = 0.8, p = 0.01), degree of expertise/confidence (Clout; d = 1.0, p = 0.002), and openness/guardedness (Authentic; d = ‐0.9, p = 0.006) (Figure 1). Differences were observed between facilitators and participants in the descriptive (Figure 1) and inferential (Figures 2&3) statistical methods employed. Differences between unstructured and semi‐structured sessions, including between different agendas in the semi‐structured sessions, were observed. Sessions 2 and 4 focused on the participant while sessions 1 and 3 focused on their loved one (Figure 2). The clustering algorithm categorised participants’ conversational turns into three groups: sharing experience (EXP), self‐reflection (SELF), and group processes (GROUP). Contribution‐types were dispersed throughout sessions (Figure 3).ConclusionResults suggest that LIWC2015 can be used to distinguish support group conversations from natural speech, facilitators from participants, and different sessions based on agenda. The methodology could be adapted for use by other peer‐support services wanting insight into their groups using only session transcripts as raw data.