bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoneurology; targeting the brain Immune system as a novel therapeutic strategy for dementia and neurodegeneration
Authors: Rosenthal Arnon 
Published: December 2022

Abstract
Immuno‐neurology: targeting the brain Immune system as a novel therapeutic strategy for dementia and neurodegenerationFor the last two decades, the predominant approach to treating neurodegenerative disorders was to remove or disaggregate disease‐typifying, misfolded proteins or prevent their synthesis. Multiple clinical trials with drugs that counteract beta‐amyloid or Tau protein in Alzheimer’s disease (AD), Alpha‐Synuclein in Parkinson’s disease, SOD1, C9orf72, and TDP‐43 in ALS, and the Htt protein in Huntington’s disease, are still in progress. An alternative broad‐based therapeutic strategy for degenerative brain disorders is to recruit the brain’s immune system to thwart multiple disease pathologies. This approach, designated immuno‐neurology, is conceptually akin to immuno‐oncology, which revolutionized cancer therapy by recruiting the immune system to counteract tumor growth. Immuno‐neurology hypothesizes that impaired activities of microglia the innate immune cells of the brain, due to normal aging or genetic mutations cause havoc in our brain’s ability to function and deal with insults and thus enable neurodegeneration. The scientific rationale for immuno‐neurology is derived from our growing understanding of the role human genetics and microglia play in the etiology of brain disorders. Human genetics revealed that while AD is characterized by synaptic and neuronal loss, many genetic variations that increase the risk to develop AD reside in genes that are specifically expressed in, and control the survival and function of, microglia. Microglia are now known to be key regulators of brain well‐being. They are responsible for the removal of misfolded proteins, myelin debris, and disease‐causing agents as well as the repair of leaky blood vessels and injured brain tissue. In addition, microglia, directly and indirectly, regulate brain function by controlling the number of synaptic connections and the survival or activity of oligodendrocytes, astrocytes, and endothelial cells. Using familial risk genes that regulate microglia, such as Progranulin, TREM2, CD33, and MS4A, as levers to repair and harness these critical brain immune cells has emerged as a promising therapeutic strategy for degenerative brain disorders.
Examining I‐CONECT Intervention Effect on Psychosocial Wellbeing
Authors: Yu Kexin , Hampstead Benjamin M. , Wild Katherine , Silbert Lisa C , Dodge Hiroko H 
Published: December 2022

AbstractBackgroundThe Internet‐based Conversational Engagement Clinical Trial (I‐CONECT, ClinicalTrials.gov:NCT02871921) intervention provided interpersonal interactions with video calls to socially isolated older adults. It is hypothesized that such intervention could improve individuals' psychosocial wellbeing by increasing social contacts. This abstract examines I‐CONECT intervention effects on psychological wellbeing outcomes.MethodThe intervention group received 30‐minute video chats 4 times/week for 6 months followed by 2 times/week for additional 6 months. The control group received weekly check‐in calls for 12 months. We used data from the baseline, six‐month and twelve‐month follow‐ups. Psychosocial outcomes were measured with NIH Toolbox Emotional Battery (NIHTB‐EB). Three domain scores, negative affect, social satisfaction, and psychological wellbeing, were calculated with 17 subscale scores weighted by factor loading. Mixed Models for Repeated Measures (MMRM) were run for the three psychosocial outcomes, controlling for age, sex, education, and experience of COVID‐19 pandemic. Participants were considered affected by COVID‐19 if any of the data points were collected after March 2020. Subsample analyses were conducted by participants' cognitive status (with normal cognition vs. MCI).ResultThe analysis included 134 participants, 70 with normal cognition and 64 with MCI. The sample’s mean age was 82.3, 44.9% were in the intervention group, 67.0% were female, the average year of education was 15.1, and 51.6% were affected by the pandemic. For the subsamples of individuals of normal cognition and MCI, we did not find any significant change in psychosocial outcomes due to the intervention. However, both intervention and control groups increased social satisfaction scores at both 6‐month and 12‐month (Table 1, Figure 1), suggesting that weekly phone check‐ins and frequent video‐chats interactions can provide the same magnitude of improvement in psychosocial wellbeing. We observed the COVID‐19 pandemic affected social satisfaction of both intervention and control groups negatively for those with MCI but did not affect the individuals with normal cognition.ConclusionBoth intervention and control groups improved in a measure of social satisfaction. Once per week 10‐minutes phone check‐ins provided for the control group seemed to be sufficient for improving social wellbeing. Implementing weekly phone check‐ins in the community might help improve psychological wellbeing among socially isolated older adults.
I‐CONECT: Efficacy in Primary and Secondary outcomes
Authors: Dodge Hiroko H , Wu Chao‐Yi , Albin Roger L. , Hampstead Benjamin M. , Kaye Jeffrey A , Wild Katherine , Silbert Lisa C 
Published: December 2022

AbstractBackgroundOctogenarians are the fastest growing segment of the population worldwide, but are often excluded from pharmacological intervention trials. Slowing cognitive decline and delaying the onset of dementia even for a few years among this age group could reduce prevalent dementia significantly. Behavioral intervention targeting the older old, which can be easily started and sustained even among the homebound, is needed.MethodBased on the epidemiological findings and promising results in our previous pilot project, we developed Internet‐based Conversational‐Engagement Clinical Trial (I‐CONECT)” (ClinicalTrial.gov: NCT02871921). I‐CONECT is a multi‐site, assessor‐blind, randomized controlled behavioral intervention trial intended to enhance cognitive reserve by increasing social interactions, specifically conversational interactions, using video conferencing. Through community outreach and mass‐mailing, 29,664 contacts were attempted, resulting in 1,139 telephone screenings. Ultimately 186 socially isolated participants aged 75 and older (mild cognitive impairment (MCI) or normal cognition (NC)) were randomized (mean age = 81.1, 20% African Americans). The experimental group engaged in 30‐minute video chats 4 times per week for 6 months, followed by twice per week for an additional 6 months, and weekly 10‐minute phone check‐ins. The control group received only the weekly phone check‐ins. Due to the COVID‐19 pandemic, we replaced in‐home assessments with telephone assessments (T‐COG) during the intervention. Accordingly, we conducted two separate analyses: one using only those who completed Month 6 assessments before the COVID pandemic (n = 56, N56Analysis) and another using all randomized participants (n = 186, N186Analysis) with the latter analysis controlling for COVID‐19 pandemic exposure using mixed models for repeated measures.ResultAmong MCI participants, global cognition as measured by the Montreal Cognitive Assessment (MoCA) (primary outcome) was 1.76 points higher at Month 6 assessments among the experimental group compared with the control group (M56analysis) (p = 0.03, Cohen’s d = 0.73). At Month 12, we also observed 2.19 points higher score (p = 0.03) in Craft Story Immediate Recall (episodic memory/encoding, secondary outcome) in M186Analysis.ConclusionDespite the reduced sample size, we demonstrated efficacy in our primary and secondary outcomes and feasibility of executing methods to enhanced social engagement in isolated older adults using a virtual platform. Long term effects of this intervention will be examined in a future Phase III trial.
Plasma biomarkers combined with UPDRS and MoCA for differential assessments of amnestic cognitive impairment (aMCI), Parkinson’s disease (PD+PDD) and dementia with Lewy body (DLB): A pilot study
Authors: Sabbagh Marwan N. , Lue LihFen , Decourt Boris , Shill Holly 
Published: December 2022

AbstractBackgroundThere would be tremendous value for having biomarker panels as screening tools for the assessment of AD and PD pathologies. Technologies that increase the sensitivity and accuracy of the measurement of plasma Aβ42, total Tau (t‐Tau), phosphorylated Tau (P‐tau),) have emerged and there is interest in testing plasm alpha synuclein (α‐syn). The specific aim of the present study was to assess the accuracy of plasma Aβ42, total Tau (t‐Tau), and α‐syn combined with clinical measures in identifying mild cognitive impaired (MCI), PD/PDD, and DLB cases.MethodsThe total sample size was 77 subjects including 37 NC, 16 MCI [NIA‐AA Criteria, Alberts 2011], 12PD/PDD [Hughes criteria] and 12 DLB [McKeith criteria]. NC subjects reported no demonstrable cognitive complaints, were intact functionally and cognitively.. The variables included age, education, MOCA, UPDRS, and H‐Y stage. Plasma biomarkers were assayed by ImmunoMagnetic Reduction (IMR) technology (MagQu, Inc).ResultsMOCA scores were lower in the aMCI and DLB groups. The UPDRS and H‐Y stage scores were significantly higher in the PD and DLB groups. The sensitivities using biomarkers (abeta42xT‐Tau) or MoCA individually to discriminate aMCI from NC are 0.625 to 0.92, respectively. The combination of biomarker and MoCA shows the 0.929 for the sensitivity. As to the specificity, individual biomarker or MoCA shows 0.778, whereas the combination of biomarker and MoCA shows 0.833. .When clinical measures were combined with biomarker values (UPDRS w/alpha‐syn; DLB status could be differentiated from PD/PDD with a sensitivity 0.955, Specificity 0 980, The combination of p‐tau181 with UPDRS had a sensitivity of 0.833 and specificity of 0.833 which was better than the sensitivity and specificity of the individual measures.ConclusionsInvestigations on the discrimination of DLB vs. PDD are rare. In this pilot study, we show that IMR assays of plasma α‐Syn, P‐tau 181, and Aβ42 x t‐tau in combination with clinical measures (UPDRS and MOCA), could differentiate PD/PDD from DLB, as well as NC from aMCI. Thus, our data suggest clinical utility of these novel biomarker modalities and panels. Differentiating DLB from PDD could be consequential in clinical characterization. Future studies will aim to replicate our findings on larger group sizes.
Circulating neurodegeneration biomarkers neurofilament light protein and p‐tau181 are increased in individuals with heart failure at risk for vascular cognitive impairment
Authors: Hoyer‐Kimura Christina , Konhilas John , Sweitzer Nancy , Ryan Lee , Hay Meredith 
Published: December 2022

AbstractBackgroundSystemic inflammation, which is present in heart failure (HF), is known to increase risk for dementia and development of vascular cognitive impairment and dementia (VCID). Both neurofilament light protein (NfL) and tau phosphorylated at threonine‐181 (p‐tau181) are well known biomarkers of neurodegeneration in both Alzheimer’s disease and non‐Alzheimer’s disease neurodegenerative diseases. The purpose of the present study was to determine if blood levels of NfL and p‐tau181 are increased in HF patients at risk for VCID.MethodWe performed a retrospective study of 58 participants from the previously completed TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist). TOPCAT participants had symptomatic HF categorized using New York Heart Association (NYHA) criteria, were > 50 years of age, and had ejection fraction (LVEF) ≥45%, assessed within 6 months from study start (n=58, 52% female). Control serum samples were obtained from age‐matched adults between 50‐85 with no known health issues (n=24, 50% female). NfL was measured using Simoa Quanterix and p‐Tau181 measured with SimoaHuman pTau‐181 V2 kit. Statistical analysis was performed using GraphPad and significance tested using Welch’s ANOVA, Dunnett’s post.ResultBaseline NfL levels were significantly higher in NYHA class I/II (n=56) and III/IV (n=54, p<.0001) than measured in age‐matched controls (see table for values). Over 12‐months follow‐up, participants in NYHA class I/II had an increase in NfL of 9.6±5% relative to baseline and those in class III/IV had a 31.7±17% increase from baseline. P‐tau181 levels were also significantly higher in both NYHA class I/II (n=56) and III/IV (n=54, p=.0002) as compared to age‐matched controls (see table for values) with levels were significantly higher in class III/IV than in class I/II participants (ANOVA, Dunnett’s post, p<.001). Levels of p‐tau181 did not show significant changes over the 12‐month time in any group.ConclusionThese results demonstrate that 2 well‐studied biomarkers of neurodegeneration, NfL and p‐tau181, are elevated in subjects with HF. Studies are underway to determine if biomarker levels correlate with measures of cognitive function and MRI measures of brain structure and function in HF patients. (Supported by NIA U01AG066623).
Novel advances in the characterization of dementia subtypes: from multi‐feature classification to whole brain computational models
Authors: Prado Pavel , Moguilner Sebastian , Herzog Ruben A , Parra‐Rodriguez Mario A , Otero Monica , Mejía Jhony Alejadro , Sainz Agustín , Taglizucchi Enzo , Ibáñez Agustin 
Published: December 2022

AbstractBackgroundBrain functional connectivity analyses derived from electroencephalography (EEG) provides relevant information for classification of dementia subtypes. The predictive strength of classification tools can be benefit from integrative, multi‐feature analysis of EEG which result in composite metric of functional connectivity. Additionally, significant improvement can be obtained when connectivity analyses consider the dependence between groups of regions as a whole system (high order interactions), instead of conceiving the network as a collection of pairwise interactions.MethodFive minutes, resting‐state EEG (rsEEG) was recorded from healthy controls (HC, n=42), and participants diagnosed with either behavioral variant frontotemporal dementia (bvFTD, n=19) or Alzheimer Disease (AD, n=33). EEG source localization analyses were conducted. Whole brain functional connectivity (82 anatomic compartments, AAL atlas) was analyzed using 17 metrics to capture different statistical dependence between source space rsEEG time series, in both time‐, and frequency‐domains. Furthermore, high‐order, non‐lineal statistical interdependencies between group of brain regions were assessed using multivariate information theory. Gradient boosting classifiers with Bayesian optimization, harmonization, and feature elimination were implemented.ResultClassification of dementia subtypes, using a particular frequency‐domain connectivity metric, displayed better performances as features for classification comprised information from multiple EEG frequency bands. Likewise, classification systems including information from several connectivity metrics outperformed those achieved with individual metrics. Dementia classification conducted with connectivity metrics derived from mutual information significantly improved as order of interaction (number of brain regions consider as a network) increased. This latter approach boosted multimodal (fMRI‐EEG) classification of dementias based on brain functional connectivity, and served as input for whole‐brain computational models describing the pathophysiology of neurodegenerative diseases.ConclusionIntegrative, composite metrics of connectivity, and connectivity analyses of source localized rsEEG based in high order interactions capture relevant information to discriminate dementia subtypes, and provide a reliable and interpretable description of brain functional connectivity and neurodegeneration.
The Need for Big Data and Large Consortiums on The Use of EEG as a Potential Tool to Decide on Which Frequency We Should Use for Sensory Entrainment in Alzheimer’s Disease?
Authors: Güntekin Bahar , Duygun Rümeysa , Bölükbaş Burcu , Yener Görsev , Erdal Furkan 
Published: December 2022

AbstractBackgroundSuccessful use of sensory 40 Hz‐gamma entrainment has been shown in Alzheimer’s Disease animal models. Few studies had used 40 Hz‐gamma sensory gamma entrainment on human subjects and there are contradictory results on these studies. We think there could be different frequency dynamics in animals and in humans. To answer this question, we aimed to analyze the dominant gamma frequency band in Alzheimer’s Disease patients, healthy young and elderly subjects. We hypothesized that the dominant gamma frequency would be different across groups being lower in AD patients.MethodEyes open and eyes closed spontaneous EEG data of 179 participants ( 59 early‐stage AD patients, 60 healthy elderly, and 60 healthy young subjects) were analyzed. Fast Fourier Transform (FFT) was applied to eyes open and eyes closed data separately. The three highest peaks of power value as the gamma dominant peak frequency were analyzed.ResultsThe results indicated that the gamma dominant peak frequency of AD patients (Mean eyes opened = 33.4 Hz, Mean eyes closed = 32.7 Hz) was lower than healthy elderly (Mean eyes opened = 35.5 Hz, Mean eyes closed = 35.0 Hz) and healthy young subjects (Mean eyes opened = 37.2 Hz, Mean eyes closed = 37.0 Hz) (p< 0,05). Furthermore, the healthy elderly group had lower gamma dominant peak frequency values than the young healthy group (p< 0,05).ConclusionThe results of the present study showed that the dominant gamma frequencies are being slower as the age increase, moreover it is even getting slower in AD patients. The dominant gamma frequency of healthy elderly age is 35 Hz for eyes closed and 35.5 Hz for eyes‐open conditions. Since the AD patients had a 32.7‐33 Hz gamma frequency range it would be adequate to use 35 Hz gamma entrainment as the dominant frequency of the healthy elderly group to normalize the slower gamma frequency band in AD patients. So rather than 40 Hz, gamma entrainment 35 Hz gamma entrainment could be more beneficial for AD subjects. To test this hypothesis, a global consortium is needed to find out the right gamma frequency in large subject groups.
Financial Altruism is Associated with Alzheimer’s Disease Neurocognitive Profile in Older Adults
Authors: Weissberger Gali H , Samek Anya , Mosqueda Laura , Nguyen Annie , Lim Aaron , Fenton Laura E. , Han Duke 
Published: December 2022

AbstractBackgroundOlder age is associated with an increase in altruistic behaviors such as charitable giving. The present study aimed to investigate the cognitive correlates of financial altruism in older adults.MethodOlder adults (N = 67; M age = 69.21, SD = 11.23; M education years = 15.97, SD = 2.51; 58.2% female; 71.6% Non‐Hispanic White) completed a comprehensive neuropsychological assessment and an altruistic choice paradigm in which they made decisions about allocating money between themselves and an anonymous person.ResultIn multiple linear regression analyses that controlled for age, education, and sex, financial altruism was negatively associated with performance on cognitive measures typically sensitive to early Alzheimer’s Disease (including word list learning and recall, delayed story recall, and animal fluency). When financial altruism responses were grouped, differences between altruistic groups revealed that individuals who gave more than they kept for themselves demonstrated the worst cognitive performance compared to those who gave equally (kept half and gave half) and those who gave less (kept more and gave less).ConclusionFindings of this study point to a negative relationship between financial altruism and cognitive functioning in older adults on measures known to be sensitive to Alzheimer’s Disease (AD). Findings also point to a potential link between financial exploitation risk and AD in older age.
Use Acetazolamide in the Complex Therapy of Alzheimer’s Disease
Authors: Sushko Viktor Vasilievich , Sushko Viacheslav Viktorovich 
Published: December 2022

AbstractBackgroundImpaired glymphatic clearance is one of the causes of Alzheimer’s disease. Acetazolamide is a drug that affects the normalization of glymphatic clearance.MethodsWe followed four women aged 65‐70 years with a diagnosis of Alzheimer’s disease in 2019‐2021. They were treated in the unit according to Alzheimer’s disease treatment standards. During periodic examination by an ophthalmologist, they were diagnosed with first‐stage glaucoma (initial) ‐ a blind spot interfering with normal peripheral vision and a deepening of the optic disc in the central zone were identified. For a glaucoma treatment, they were prescribed Acetazolamide 125 mg once a day in the morning for 7 days with weekly monitoring of intraocular pressure. They also received Asparkam, 1 tablet, 3 times a day during Acetazolamide administration to prevent a deficiency of potassium ions in the body. On days 12‐14 after normalization intraocular pressure, Acetazolamide administration was discontinued. To monitor the dynamics of cognitive impairment, patients on the unit underwent Trail Making Test Parts A & B paper‐pencil versions every month.ResultsBefore glaucoma treatment, the patients' Trail Making Test Parts A speeds were 84, 87, 90, and 92 seconds. The speed of Part B was 270, 300, 293, and 305 seconds. After two weeks of glaucoma treatment, patients again completed the Trail Making Test Parts A & B paper‐pencil versions. The patients' speeds for Part A were 60, 68, 63, and 70 seconds. The speeds in Part B were 180, 190, 217, and 194 seconds.ConclusionAdministration of Acetazolamide has a positive effect on patients with cognitive deficits and can be successfully used as part of the complex therapy of Alzheimer’s disease.