bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproducible Python workflow for multi‐site resting‐state EEG analysis: From raw data to group classification
Authors: Jaramillo‐Jimenez Alberto , Mantilla‐Ramos Yorguin Jose , Tovar Diego , Ochoa John F , Brønnick Kolbjørn , Aarsland Dag , Bonanni Laura
Published: December 2023

Background

Among promising markers for neurodegenerative disorders, electroencephalogram (EEG) represents a non‐invasive and potentially portable alternative. Standardized methods for preprocessing may contribute to less inter‐observer variability, while pooling multi‐centric EEG data may provide more generalizable results. We aim to formulate a reproducible pipeline for group‐level classification (of Parkinson’s Disease ‐PD‐) based on various features of resting‐state EEG recordings (rsEEG) collected in multi‐site studies.

Methods

We used four datasets (acquired in Colombia, Finland, and the USA) consisting of 169 subjects (84 PD; 85 non‐PD healthy controls). Our workflow included rsEEG raw files standardization, preprocessing, spectral bandpowers and multiple entropy features extraction on sensor space, harmonization of multi‐site features, and group‐level multiclass classification using supervised machine learning methods. Center/scanner‐related variability effects in the extracted features were harmonized using the ComBat approach and its variants 1. Finally, sequential feature selection (SFS) and binary classification (Non‐PD vs. PD) was conducted using XGradientBoosting 2. The full workflow is detailed in Figure 1.

Results

t‐distributed stochastic neighbor embedded (tSNE) plots showed that center‐related variability in spectral features was reduced after harmonization using the ComBat method and its bootstrapped variant, Figure 2. SFS of rsEEG features was performed on 224 harmonized features, showing the highest performance when alpha, pre‐alpha, and slow‐theta bands were considered for subsequent classification. The XGradientBoosting classifier showed an AUC of 0.826 in separating PD from non‐PD, Figure 3.

Conclusions

In multicenter studies, the harmonization of rsEEG features at the sensor space using ComBat can contribute to controlling batch effects. XGradientBoosting with rsEEG features and SFS performed well in classifying non‐PD vs. PD.

Intended to be a practical tool for group‐level analysis of neurodegenerative disorders based on sensor space rsEEG features, our workflow is openly available at (https://github.com/alberto‐jj/raw_to_classification) and can be easily adapted to multi‐class classification and regression tasks.

References

1. Da‐ano, R., et al. Sci. Rep.
10, 10 (2020).

2. Moguilner, S., et al. J. Neural Eng.
19, 046048 (2022).
Anti‐amyloidogenic effect of BACE1 expression lowering compound identified using high‐throughput gene promoter assay
Authors: Byun Yujung , Baek Seung Hyun , Jo Dong‐Gyu
Published: December 2023

Background

Accumulation of Aβ in a brain is one of the pathological hallmarks of Alzheimer’s disease (AD). Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β‐secretase (BACE1) and γ‐secretase complex. BACE1 is one of the crucial targets for AD given that BACE1 expression is significantly upregulated in AD patients compared with non‐AD. However, direct and complete inhibition of BACE1 activity can cause unpredictable or unintended effects because of numerous physiological substrates of BACE1.

Method

We screened small compounds, including drugs approved by the U.S. Food and Drug Administration to identify medicines that reduce promoter activity of BACE1. TG reduced the levels of BACE1 protein and mRNA in APP‐SH‐SY5Y cells. In order to confirm the effect of TG regulating the expression BACE1, we constructed the RFP (BACE1 expression indicator) ‐GFP (cell body) U2OS cell line and compared the TG and analogs. After administration of TG,we carried out Morris Water Maze(MWM) test in APP/PS1 AD model mice. We did immunofluorescence assay in each group of mouse brains. We conducted an ELISA assay to determine quantitative changes in Aβ accumulation.

Result

We have found a new candidate drug that reduces promoter activity, mRNA, and protein levels of BACE1 in neuronal cells. We have confirmed that the drug decreases the BACE1 gene expression, prevents accumulation of Aβ, and improves cognitive function in APP/PS1 transgenic mice.

Conclusion

The ability of this compound reverses a wide range of deficits suggests that BACE1 expression reducing agents may have therapeutic utility in the treatment of AD
Effects of creative expression program on patients with mild cognitive impairment: based on Transcranial Doppler
Authors: Zhao Junyu , Baoying Zhang , Rong Lin , Lili Chen , Yuanjiao Yan , Lijuan Yu , Hong Li
Published: December 2023

Background

In this study, patients with mild cognitive impairment (MCI) were treated with the creative expression program (CrExp) and assessed for changes in cognitive function, while the correlation between changes in cognitive function and cerebral hemodynamic parameters was explored based on Transcranial Doppler (TCD) ultrasound.

Method

We studied 35 older adults with MCI aged 60 years or older. A creative expression program (CrExp) intervention was implemented in these 35 older adults with MCI for a total of 24 intervention sessions lasting approximately 0.5‐1 hour each over 24 weeks. All participants underwent a pre‐and post‐intervention MoCA to assess and compare changes in the cognitive function of patients before and after the intervention. And their cerebral hemodynamic parameters were measured by (TCD) ultrasound after the intervention.

Results

After the intervention, MCI patients treated with CrExp had significantly higher cognitive function scores than before the intervention (MoCA; t = ‐2.15, P = 0.036). TCD parameter measurements showed that the mean blood flow velocity (MBFV) and the resistance index (RI) values of the vertebral artery (VA), the basilar artery (BA), and the middle cerebral artery (MCA) in MCI patients were significantly lower than the normal mean (P<0.05), while the pulsatility index (PI) values of VA and MCA were significantly higher than the normal mean(P<0.05). MBFV in MCA was positively correlated with changes in cognitive function, whereas RI was negatively correlated with changes in cognitive function(P<0.05).

Conclusions

This study provides evidence that the CrExp intervention is effective in improving cognitive function in patients with MCI, while transcranial Doppler ultrasound can provide an objective basis for the diagnosis of mild cognitive impairment and can be tested by TCD ultrasound to determine the correlation between the effect of the cognitive intervention and changes in hemodynamic parameters.

Keywords

Mild cognitive impairment (MCI); Creative expression program intervention (CrExp); Transcranial Doppler (TCD) ultrasound.
Exploring the association between VLOM ratio and years of education in MCI and normal aging urban cohort
Authors: R Meghana , Malo Palash Kumar , Mallikarjun Divya N , Stezin Albert , Narayanasamy Rajitha , Menon Meenakshi , Lingegodwa Abhishek Mensegere , Partha Ajith , Velavarajan Goutham , Hameed Shafeeq K Shahul , HS Sunitha , M Amitha C , Singh Sadhana , Arvind Prathima , Diwakar Latha , Kommaddi Reddy Peera , Sundarakumar Jonas S. , Issac Thomas Gregor
Published: December 2023

Background

Mild Cognitive Impairment (MCI) is a transition state of cognitive decline from healthy brain to dementia. It is a prodrome of Alzheimer’s disease. Verbal‐Language/Orientation‐Memory (VLOM) ratio, a simply calculated index compares its language and memory scores helps to differentiate between Alzheimer’s disease and frontotemporal dementia (Mathuranath, et al.,2000). VLOM ratio is helpful in prognosticating and planning future management of the disease. The previous studies have shown the association of scores in cognitive domains with years of education (Nieto A, et al.,2016). Therefore, the objective of the study is to explore the association of years of education with VLOM ratio in MCI participants and normal participants.

Method

Cross sectional analysis was done using the baseline data from the cohort study Tata Longitudinal Study of Ageing (TLSA) from urban Bengaluru, India. Clinical dementia rating scale (CDR) was used to classify participants into normal and MCI category. CDR score of 0 was considered as normal, score of 0.5 as MCI. ACE III‐R (Addenbrooke’s Cognitive Examination III‐R) a neuropsychological test was administered and verbal fluency plus language to orientation plus memory (VLOM) ratio was calculated. Further, years of education was classified into three levels and comparison of VLOM ratio was made within these levels of education groups in both MCI and normal participants. Mann Whitney U test was used to compare the VLOM ratio between MCI and normal participants. VLOM ratio and years of education among the MCI and normal participants was compared using Kruskal‐Wallis test.

Results

Among 953 participants, 69 had MCI and 884 participants had normal cognition. Comparison of VLOM ratio between MCI and normal participants showed a significant difference, with higher VLOM ratio in MCI participants (Median (IQR)) = 0.97 (0.11) vs 0.95 (0.09); p = 0.01). There was no significant difference in VLOM ratio between years of education in both normal and MCI participants.

Conclusion

The VLOM ratio found to be higher in MCI group indicating that the scores in orientation and memory domain might be lower in MCI compared to Normal participants. There was no association of VLOM ratio with years of education in normal and MCI participants.
Keep your brain healthy: development and evaluation of an e‐learning tool on dementia risk reduction
Authors: Van Asbroeck Stephanie , Wimmers Sophie C.P.M. , van Boxtel Martin P.J. , Köhler Sebastian , Deckers Kay
Published: December 2023

Background

Many people are unaware of the potential for dementia risk reduction, but state they would appreciate more information on this topic (1). Raising awareness is important as a first step towards behavior change (2). The knowledge that a set of lifestyle behaviors is beneficial for your cognitive health may also provide additional motivation (2).

Method

An online, free e‐learning on the topic of dementia risk reduction for the Dutch adult population will be developed (in co‐creation with Alzheimer Netherlands). It will cover the following topics: physical activity, healthy diet and alcohol consumption, cognitive activity, mental wellbeing including social wellbeing and sleep, cardiovascular health, and tips from lifestyle coaches and end‐users on how to make sustainable lifestyle changes. The content of the e‐learning will be delivered in stages, so that completion of the full course takes approximately seven weeks.

Result

The e‐learning’s effectiveness in terms of knowledge acquisition, evolution in motivation for health behavior and actual health behavior improvements will be assessed with validated questionnaires in a pre‐post study. Participants (minimum N = 300) will complete an online survey before starting the course, immediately thereafter and again three months later. User experiences and engagement with the e‐learning materials will also be evaluated.

Conclusion

Awareness of the potential for dementia risk reduction is currently lacking in the general population. An e‐learning is a low‐level means that can be used to increase knowledge and awareness, and could further easily be implemented as a stand‐alone tool or as part of current or future dementia risk reduction initiatives.

References

1. Heger I, Kohler S, van Boxtel M, de Vugt M, Hajema K, Verhey F, et al. Raising awareness for dementia risk reduction through a public health campaign: a pre‐post study. BMJ Open. 2020;10(11):e041211.

2. Rosenberg A, Coley N, Soulier A, Kulmala J, Soininen H, Andrieu S, et al. Experiences of dementia and attitude towards prevention: a qualitative study among older adults participating in a prevention trial. BMC Geriatr. 2020;20(1):99.
Ethnic Variation in Modifiable Risk Factors for Dementia
Authors: Bothongo Phazha LK , Waters Sheena , Chandra Avinash , Uchegbu Ijeoma , Jeraldo Rosario Isabel Espinoza , Anjum Rifah , Byford Michelle , Livingston Gill , Marshall Charles R , Mukadam Naheed
Published: December 2023

Background

We aimed to estimate the population attributable fraction (PAF) of 12 modifiable risk factors (defined by the Lancet Commission 2020), for incident dementia cases in the UK Biobank (UKB), stratified by ethnicity. We considered if ethnic differences in dementia risk, were accounted for by modifiable risk factors. To identify appropriate priorities in dementia prevention, tailored to ethnicity.

Method

The UKB is a cohort study with 502,656 volunteer participants registered between 2006‐2010, aged 40‐60 years at baseline, and followed for up to 16.8 years. To estimate the PAF of 12 modifiable risk factors (diabetes, hypertension, depression, hearing loss, obesity, traumatic brain injury (TBI), less education, social isolation, physical inactivity, air pollution, and smoking), we first estimated hazard ratios (HRs)(adjusted for age, gender, and Townsend quintiles), or when ethnicity interacted with risk factors, then we estimated HRs stratified by ethnicity. HRs were then converted to relative risk for PAF calculation.

Results

6,624 incident cases of dementia developed in 1.3%(95%CI = 1.3‐1.3)(n = 6316/471297){of Whites}, in 1.3%(95%CI = 1.1‐1.5)(n = 104/8031){of Blacks}, and in 1.0%(95%CI = 0.8‐1.2)(n = 79/8001){of South Asians (S.Asian)}. The mean age at dementia diagnosis was 71.6 years(SD,6.1){in S.Asians}; 71.8 years(SD,6.8){in Blacks}; and 73.6 years(SD,5.5){in Whites}. The combined PAF(95%CI) for dementia were: 35.6%(35.5‐35.8){in Whites}, 33.9%(32.8‐34.9){in Blacks}, and 41.0%(39.9‐42.0){in S.Asians}. The highest individual PAFs in each ethnic group, compared to the rest, were as follow. Blacks and S.Asians, respectively, for midlife hypertension: 9.6%(9.0‐10.3) and 10.1%(9.5‐10.8) vs 6.5%(6.4‐6.5){in Whites}. S.Asians for (1)Depression: 8.5%(7.9‐9.1) vs 4.0%(3.6‐4.4){in Blacks}, and 5.8%(5.7‐5.9){in Whites}; (2)Diabetes: 6.0%(5.4‐6.5) vs 5.1%(4.6‐5.6){in Blacks}, and 3.5%(3.4‐3.5){in Whites}; (3)Excessive alcohol: 1.4%(1.2‐1.7) vs 0.0%{in Blacks and Whites}. Whites for (1)Hearing loss: 3.6%(3.6‐3.7) vs 2.4%(2.1‐1.8){in Blacks}, and 3.0%(2.6‐3.4){in S.Asians}; (2)TBI: 2.5%(2.4‐2.5) vs 1.3%(1.1‐1.6){in Blacks}, and 1.7%(1.4‐2.0){in S.Asians}; (3)Less education: 5.0%(4.9‐5.1) vs 3.3%(2.9‐3.7){in Blacks}, and 3.2%(2.9‐3.6){in S.Asians}; (4)Physical inactivity: 2.6%(2.6‐2.7), vs 2.1%(1.8‐2.5){in Blacks}, and 2.2%(1.8‐2.5){in S.Asian; (5)Social isolation: 2.3%(2.2‐2.3) vs 1.9%(1.6‐2.1){in Blacks}, and 1.9%(1.6‐2.2){in S.Asians. The remaining risk factor PAFs did not differ between all ethnic groups.

Conclusion

In this relatively wealthy, and healthy population, there remain ethnic disparities in the effect of modifiable risk factors on dementia. Interventions for midlife hypertension are a priority in South Asians and Blacks, particularly depression and alcohol consumption in South Asians.
Baseline thyroid hormone levels are not associated with cognitive decline: the ELSA‐Brasil study
Authors: Gonçalves Natalia G , Szlefj Claudia , Lotufo Paulo A , Bensenor Isabela M , Suemoto Claudia Kimie
Published: December 2023

Background

Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. Additionally, most studies have been conducted in high‐income countries. The aim of this study was to investigate the longitudinal association between baseline thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels with cognitive decline in the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) during 8 years of follow‐up.

Method

Participants were evaluated every four years in three study waves (2008‐10, 2012‐14, and 2017‐19). Baseline TSH, FT4, and FT3 were collected after overnight fast and analyzed using immunoenzymatic assay. Cognitive performance was evaluated using the immediate and late recall, semantic and phonemic verbal fluency, and the trail‐making tests. A global composite z‐score was derived from these tests. Association of TSH, FT4 and FT3 levels with cognitive decline over time was evaluated using linear mixed‐effects models, adjusted for sociodemographic, lifestyle, and clinical variables.

Result

In 9,524 participants (mean age 51.2±8.9 y, 51% women, 52% White), the mean baseline TSH level was 2.3 ± 1.3 mIU/L, the mean baseline FT4 level was 1.2 ± 0.1 ng/dL, and the mean FT3 level was 0.2 ± 0.04 pg/mL (Table 1). There was no association between circulating TSH, FT4, and FT3 levels and cognitive decline during the follow‐up (Table 2 and Figure 1).

Conclusion

Thyroid hormone levels were not associated with cognitive decline in middle‐aged and older adults without overt thyroid dysfunction during 8 years of follow‐up.
An update on mobile phone applications collecting data among subjects with or at risk of dementia
Authors: Piendel Lydia A , Hort Jakub , Vališ Martin
Published: December 2023

Background

The ubiquity of smart mobile phones is increasing worldwide, creating an opportunity for telemedicinal use by screening people at risk of or with dementia through monitoring daily routines, behaviors, and cognitive changes. Data logged or tracked in an app and analyzed with machine learning (ML) could be shared with physicians and specialists to allow for screening, follow‐up, and timely diagnoses, and could provide users information on preventive measures or disease management. This review comments on existing evidence of mobile device applications designed to passively and/or actively collect data on cognition relevant for Alzheimer’s disease (AD) and other dementias.

Method

The PubMed database was searched to identify existing literature on applications related to dementia and cognitive health data collection. The search deadline was December 1, 2022. Criteria for inclusion was limited to articles in English which referenced data collection via mobile app from adults 50+ concerned, at risk of, or diagnosed with dementia.

Result

We identified relevant literature (n = 25) which fit our criteria. A common theme among excluded literature was the mention of apps that provide users, primarily caregivers, with cognitive health information but fail to collect data. We found the existing library of data collecting dementia‐related apps has existed for several years yet remains underdeveloped; however, it may serve as proof of concept and feasibility as there is much supporting evidence on their predictive utility.

Conclusion

Concerns about the validity of mobile apps for cognitive screening and privacy issues remain prevalent. Mobile applications and use of ML is widely considered a financially and socially viable method of compiling symptomatic data but currently this large potential dataset, telemedicine communication tool, and research resource is still largely untapped.
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

Background

In 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.

Method

In 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).

Result

The 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).

Conclusion

Electrophysiological 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

Background

To explore the relationship between network vulnerability and longitudinal atrophy progression in FTLD spectrum, using Network Diffusion Model (NDM) of pathology spread.

Method

Thirty‐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.

Result

In 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.

Conclusion

The 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

Background

In 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.

Method

AD 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.

Result

Prior 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.

Conclusion

Our 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

Background

Picture 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.

Method

We 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.

Result

SAND, 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.

Conclusion

A 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

Background

Most 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.

Method

We 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.

Result

Anxiety (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.

Conclusion

NPS 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

Background

While 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.

Method

In 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.

Result

Plasma 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).

Conclusion

Results 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

Background

The 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.

Method

The 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.

Result

48,5% 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).

Conclusion

Availability 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

Background

Spousal 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.

Method

We 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.

Result

Whole‐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).

Conclusion

Results 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

Background

Quantitative 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.

Method

In 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.

Result

Meaningful 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).

Conclusion

Results 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.
Comparing the distribution of neuropsychiatric symptoms among individuals with depression and mild cognitive impairment
Authors: Keng Alvin , Kapustin Daniel , Ma Clement , Bingham Kathleen , Fischer Corinne E. , Mah Linda , Gallagher Damien , Butters Meryl A. , Bowie Christopher R , Voineskos Aristotle N. , Graff‐Guerrero Ariel , Flint Alastair , Herrmann Nathan , Pollock Bruce G. , Mulsant Benoit H. , Rajji Tarek K. , Kumar Sanjeev
Published: December 2023

Background

Neuropsychiatric symptoms (NPS) are common during the course of neurocognitive disorders. NPS have been previously reported in early and late stages of Alzheimer’s Disease. However, our understanding of NPS in high‐risk states for dementia such as mild cognitive impairment (MCI) and major depressive disorder (MDD) is poor. The purpose of this study was to compare the frequency and factor structure of neuropsychiatric symptoms among individuals with Mild Cognitive Impairment (MCI), Major Depressive Disorder (MDD) in remission, and comorbid MCI and MDD (in remission) (MCI‐D).

Method

We used baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt‐MD) study, a multicenter trial across five academic sites in Toronto, Canada (clinical trial No. NCT0238667). We used ANOVA or χ2‐test to compare frequency of NPS across groups. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI‐Q) items in the three groups.

Result

We included 374 participants with a mean age of 72.0 years (SD = 6.3). In the overall sample, at least one NPS was present in 64.2% participants, and 36.1% had at least moderate severity NPS (36.1%). Depression (54%, χ2 < 0.001) and apathy (28.7%, χ2 = 0.002) were more prevalent in the MCI‐D group as compared to MCI and MDD groups. In factor analysis, NPS grouped differently in MCI, MDD, and MCI‐D groups. A “psychotic” subgroup emerged among MCI and MCI‐D, but not in MDD. Night‐time behaviors and disinhibition grouped differently across all three groups.

Conclusion

Prevalence of NPS seems higher in persons with MCI‐D as compared to those with only MCI or MDD. The factor structure of NPS differed between MCI, MDD, and MCI‐D groups. Future studies should investigate the association of NPS factors with cognition, function, and illness biomarkers.
Rural‐Urban differences in the prevalence of depression and anxiety among middle‐aged and older Indians
Authors: H Aishwarya B , Rai Pooja , Malo Palash Kumar , Hameed Shafeeq K Shahul , Stezin Albert , Arvind Prathima , Lingegodwa Abhishek Mensegere , Mallikarjun Divya N , Narayanasamy Rajitha , Menon Meenakshi , R Meghana , M Amitha C , Partha Ajith , Velavarajan Goutham , Singh Sadhana , Issac Thomas Gregor , Sundarakumar Jonas S.
Published: December 2023

Background

Depression and anxiety have a considerably adverse impact on physical, mental and cognitive abilities. Since rural communities generally have more difficult living circumstances than urban communities, it is likely that prevalence of depression and anxiety could be higher in the rural population. Socio‐demographic factors, such as gender and age could also significantly influence the prevalence of these conditions. This study aims to examine the above potential differences.

Method

This was a cross‐sectional study which included participant’s ≥45 years, of both genders, who were recruited as part of two ongoing, prospective, aging cohort studies – Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) in rural India and Tata Longitudinal Study of Aging (TLSA) in urban India. Baseline clinical data of SANSCOG (rural) and TLSA (urban) participants was utilized. Geriatric Depression Scale (GDS‐30) and Generalized Anxiety Disorder scale (GAD‐7) were used to estimate the prevalence of depression and anxiety, respectively. Statistical analysis was performed using Binomial test to determine differences in prevalence of depression and anxiety between the two populations as well as gender and age group‐wise differences.

Result

Overall prevalence of depression was significantly higher among rural (16.13%) than urban population (8.2%, p<0.001). Similar trend was seen for prevalence of anxiety (rural = 5.27%, urban = 2.42%, p = 0.002). Also, prevalence of depression was significantly higher among females than males in both rural (20% vs. 12%, p = <0.001) and urban participants (11% vs. 5%, p = 0.0003). Prevalence of anxiety was also significantly higher among females than males in rural (6% vs. 4%, p = 0.01) but not significantly different in urban population (3% vs. 2%, p = 0.36). There was no significant difference between the two age groups in either of the populations for depression (rural: <65 = 15% vs. ≥65 = 18%, p = 0.92 and urban: <65 = 9% vs. ≥65 = 7%, p = 0.18) or anxiety (rural: <65 = 6% vs. ≥65 = 4%, p = 0.12 and urban: <65 = 2% vs. ≥65 = 3%, p = 0.81).

Conclusion

Rural Indians had significantly higher prevalence of depression and anxiety than their urban counterparts. Women in both these populations had significantly higher burden than men. However, no age group‐wise differences were observed. Public health initiatives to address the high burden of depression in rural Indian women are urgently needed.