bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between depressive symptom severity and functional status in patients with mild cognitive impairment
Authors: Won Wangyoun 
Published: December 2023

AbstractBackgroundAlthough depression is a common co‐morbid disorder in patients with mild cognitive impairment (MCI), not all patients with MCI exhibit depressive symptoms. This study aimed to investigate the effect of depression on cognitive and functional decline in MCI.Method281 patients with MCI (MCI) defined by 0.5 score on Clinical Dementia Rating were included in the study. Patients were divided into three groups based on their Geriatric Depression Scale (GDS) scores: MCI without depression (GDS<10, n = 50), MCI with mild depression (GDS10∼19, n = 120), and MCI with severe depression (GDS>20, n = 111). Cognitive function tests (cognitive domains in CERAD‐K including letter fluency, trail making test‐A and B, and verbal learning test) and Blessed Dementia Scale‐Activities of Daily Living (BDS‐ADL) were measured. Group differences were analyzed using an analysis of variance (ANOVA). Correlation between GDS scores and BDS‐ADL were analyzed.ResultAn ANOVA test showed that activities of daily living differed significantly across groups (F(2, 276) = 13.53, p<0.001). Post‐hoc analysis showed MCI with severe depression had a significantly higher mean BDS‐ADL score compared with both MCI without depression and MCI with mild depression (both, p<0.001). Correlation analysis showed significant positive correlation between GDS and BDS‐ADL (r = 0.366, p<0.001). However, mean scores of cognitive function tests were not different among three groups.ConclusionThe present study suggests that co‐morbid depressive symptoms may have negative impact on functional status in patients with MCI. This may further suggest the importance of evaluation and treatment of depressive symptoms in patients with MCI.
Possible role of gut derived metabolites in communication between systemic inflammation and CNS in delirium development.
Authors: Trzpis Monika 
Published: December 2023

AbstractBackgroundDementia and delirium are strongly correlated. Patients with dementia are more prone to develop delirium, while delirium can lead to accelerated cognitive decline. Biomarkers present in the CSF have been considered to belong to the pathophysiological pathways between systemic inflammation, neuroinflammation, gut microbiota and consequently, contribute to the etiology of both the cognition impairments, ie. delirium and dementia. Despite multiple studies on inflammatory biomarkers in CSF, the link with systemic inflammation has still not been deciphered. Multiple studies have indicated that inflammatory pathways in patients with cognitive decline are mediated by gut microbiota.MethodIn this narrative review we screened PubMed for studies, where neuroinflammatory biomarkers detected in CSF were investigated in relation to delirium. We will explain the link to microbiome by comparing these delirium studies to microbiome studies in dementia. These studies were published in English till January 2023.ResultWe found that in patients with Alzheimer’s disease (AD) and delirium altered levels of at least 70 different neuroinflammatory biomarkers in CSF were found. Also altered microbiome has been identified in AD and its correlation with the CNS inflammation was shown. Interestingly, in case of AD, a recent study demonstrated that a microbial‐derived metabolite, trimethylamine N‐oxide (TMAO), reaches the CNS and that its elevated levels are present in AD patients.In case of delirium, we found two studies indicating contribution of disbalanced gut microbiota in acute CNS inflammation in human. It has been shown that preoperative status of gut microbiota can allow prediction of postoperative delirium in patients with gastric cancer. Interestingly, there was already one case described where fecal microbiota transplantation ameliorated patient’s infection and delirium. No studies on microbiome‐derived metabolites, which could constitute a possible link with the acute inflammation of CNS in delirium, have been found.ConclusionThere is irrefutable evidence that altered levels of neuroinflammatory biomarkers in CSF are associated with pathology of both AD and delirium. Implication of the microbiome, and microbial‐derived metabolite TMAO in inflammatory processes and in pathophysiology of AD has already been found. This has encouraged us to investigate the role of TMAO in the acute CNS inflammatory condition, i.e. delirium.
The circulating sclerostin as a biomarker for brain white matter damage in hemodialysis patients
Authors: Lin Yi‐Ting , Lin Hsiu‐Fen , Wu Ping‐Hsun 
Published: December 2023

AbstractBackgroundPatients with kidney disease, especially those receiving hemodialysis, presented a higher risk of cognitive impairment and brain white matter damage than those without kidney disease. Previous research suggests an association between lower bone marrow densities and cognitive impairments. However, the study investigating the relationship between bone turnover biomarkers and brain white matter damage in hemodialysis patients is sparse.MethodsThe enrolled hemodialysis participants were examed on the Fazekas scale of brain magnetic resonance imaging (MRI) white matter lesions and measured 8 bone turnover proteins using the Luminex bead‐based multiplex assay. The Fazekas scale of periventricular lesions was from grade 0 to grade 3. Multivariable ordinal regression and logistic regression models were examined to determine the independent relationship between bone turnover proteins and the Fazekas scale of periventricular lesions.ResultsIn 59 hemodialysis patients, older patients had more periventricular lesions on the Fazekas scale, which was connected with a worse Mini‐Mental State Examination score (MMSE). The serum level of sclerostin, one of eight bone turnover proteins, displayed a dose‐response relationship (P value for trend = 0.004), meaning that a greater sclerostin level was connected with a lower grade on the Fazekas scale. Both the ordinal regression model (odds ratio [OR] 0.886; 95% confidence interval [CI] 0.828‐0.947, P value 0.001) and the logistic regression model (odds ratio [OR] 0.828; 95% 0.712‐0.963, P value = 0.014) determined a negative association between sclerostin and the Fazekas scale of periventricular lesions after complete adjustment for potential confounders.ConclusionsThe brain white matter damage was inversely correlated with the level of circulating sclerostin. Our finding suggested a possible connection between bone turnover proteins and brain damage.
Multiple sensory impairments in relation to cognitive function: two nationwide cross‐sectional studies
Authors: Wang Binghan , Chen Hui , Shen Jie , Zhong Wansi , Zheng Yan , Lou Min , Tong Lusha , Yuan Changzheng 
Published: December 2023

AbstractBackgroundSensory impairments (SIs, including visual, hearing, olfactory, and taste impairments) have been individually associated with age‐related cognitive function. Little is known regarding their combined associations with cognitive function.MethodWe included 2,931 participants (mean age of 69.1 years) from the National Health and Nutrition Examination Survey (NHANES, 2011‐2014) and 10,785 participants (mean age of 70.2 years) from the National Health Interview Survey (NHIS, 2021). Status of visual, hearing, olfactory, and taste functions were self‐reported in structured questionnaires. In NHANES, cognitive function was objectively measured by a battery of tests, including memory, verbal fluency, and processing speed. NHIS participants answered a single question about their subjective cognitive complaints (SCC). We used regression models to assess the relation of total number of and the specific sensory impairments to z‐scores of cognitive domains (linear regression) in NHANES and with SCC (logistic regression) in NHIS.ResultA larger number of SI was related to poorer domain‐specific cognitive function (all P‐trend <0.05), including memory (beta each additional SI = ‐0.12, 95% confidence interval: ‐0.17 to ‐0.08), verbal fluency (‐0.05, ‐0.10 to ‐0.01), and processing speed (‐0.13, ‐0.16 to ‐0.09). In NHIS, each additional SI was related to 96% higher odds of SCC. We also observed independent associations of multiple sensory impairments (except olfactory impairment) with specific domains of cognitive function. In addition, each specific SI showed significant relations to higher odds of SCC (the odds ratios ranged from 1.30 to 1.78).ConclusionA larger number of SI was related to worse cognitive function and higher odds of subjective cognitive complaints.
Dietary antioxidants, cognitive impairment and dementia: a systematic review and dose‐response meta‐analysis
Authors: Zheng Ying , Chen Xiao , Yi Qian , Lu Mengxi , Huang Liyan , Tao Yang , Dong Sitong , Chen Hui , Rong Shuang , Song Peige , Yuan Changzheng 
Published: December 2023

AbstractBackgroundDietary antioxidants have been postulated to prevent age‐related cognitive decline. However, the optimal antioxidant level for cognitive benefits remains unknown.MethodMEDLINE, Embase, and PubMed were searched from inception to 5th September 2021 for cohort studies reporting the associations between the levels of dietary antioxidant, including flavonoids, vitamin E, carotenoids, and vitamin C and cognitive impairment, and dementia. The quality of all studies was assessed by the NHLBI Study Quality Assessment Tool. Random‐effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Dose‐response meta‐analysis using the Greenland and Orsini method with random‐effects models were performed.ResultA total of 14 cohort studies were included in the meta‐analysis. Comparing highest to lowest dietary intake levels, flavonoids was associated with lower odds of cognitive impairment and dementia (RRQ4 vs. Q1 = 0.84, 95% CI = 0.72–0.98), while no significant association was observed for vitamin E, carotenoids and vitamin C (RRQ4 vs. Q1 = 0.86, 95% CI = 0.58–1.27, RRQ4 vs. Q1 = 0.84, 95% CI = 0.64–1.10, RRQ4 vs. Q1 = 0.87, 95% CI = 0.68–1.11, respectively). In dose‐response analysis, a J‐shaped relation was observed for dietary vitamin C intake with protective associations detected for less than 85 mg/day intake (P<0.05 for non‐linearity). Meanwhile a significant linear protective relation was observed for dietary carotenoids (range, 0‐20mg/day, RR = 0.98, [0.95‐1.00] for each 1mg/day increment) (P<0.05 for linearity).ConclusionThe meta‐analysis results suggest potential beneficial roles of long‐term intake of dietary flavonoids, carotenoids and vitamin C in the primary prevention of cognitive impairment and dementia.
Associations Between Lifetime Musical Activity and Resting‐State Functional Connectivity in Higher‐Order Brain Networks
Authors: Liebscher Maxie , Dell'Orco Andrea , Böttcher Adriana , Peters Oliver , Priller Josef , Schneider Anja , Fließbach Klaus , Wiltfang Jens , Jessen Frank , Duzel Emrah , Buerger Katharina , Perneczky Robert , Teipel Stefan , Laske Christoph , Spottke Annika , Wagner Michael , Heneka Michael T. , Wolfsgruber Steffen , Roeske Sandra , Wirth Miranka 
Published: December 2023

AbstractBackgroundEngagement in complex leisure activities, such as playing a musical instrument, may help preserve cognitive and brain health in older age (e.g. Böttcher et al., 2022). In this study, we investigated the associations between leisure‐time musical activity and resting‐state functional connectivity (RSFC) in three higher‐order networks, the Default Mode. Fronto‐Parietal and Salience Networks, in older adults.MethodIn total, 130 cognitively unimpaired older (aged 60 years and older) participants of the DZNE ‐ DELCODE (Jessen et al., 2018) were assessed. Two groups matched for their reserve proxies were identified (with musical activity during life: n = 65 and controls: n = 65) based on self‐reported musical instrument playing during life, as measured by the Lifetime of Experiences Questionnaire. The two groups were compared in global and local (seed‐to‐voxel) RSFC patterns using pre‐specified seeds of the three brain networks. A mediation analysis explored the interrelations between lifetime musical activity, RSFC, and cognitive composites (Wolfsgruber et al., 2020).ResultOlder participants with musical activity showed higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal regions, namely the bilateral temporal poles as well as the right inferior and middle temporal gyrus, compared to controls (see Figure 1). There were no group differences in global RSFC of the three networks and no mediation effects of musical activity‐related RSFC on global and domain‐specific cognition.ConclusionWe show that self‐reported lifetime musical activity relates to higher RSFC between frontal and temporal core regions of the Default Mode Network in older adults. The finding implies that playing a musical instrument during life may help preserve neural functioning in a key network that is vulnerable to aging and AD.
References:Böttcher et al. Frontiers in Psychology 2022.Jessen et al. Alzheimer’s Research & Therapy 2018.Wolfsgruber et al. Neurology 2020.
Neuronal hyperexcitability in AD
Authors: Ranasinghe Kamalini G 
Published: December 2023

AbstractBackgroundBecause neuronal and network deficits are the imperative immediate consequences of pathological changes of disease mechanisms, neurophysiological manifestations associated with Aβ and tau are uniquely positioned to demonstrate the abnormal homeostatic and maladaptive circuit alterations and the dynamic integrated effects of underlying genetics and neuropathological changes in Alzheimer’s disease (AD). Importantly, network dysfunction manifesting as abnormal hyper‐ as well as hypo‐active oscillatory brain rhythms is detectable even during the prodromal phase of disease. Here we leveraged the higher spatial and precise temporal resolution of Magnetoencephalography (MEG) to define frequency‐specific and region‐dependent patterns of oscillatory deficits in AD patients, and to demonstrate the earliest neurophysiological abnormalities associated with AD neuropathology and their mechanistic relationships to network hyperexcitability.MethodWe studied the resting brain oscillations in individuals with AD‐spectrum (n = 88) and age‐matched controls (n = 70) using MEG. In addition, subsets of participants were evaluated with positron emission tomography (PET) with Aβ and tau specific tracers and fluid biomarker including plasma P‐tau181 and Neuro‐Filament‐Light (NFL). We used statistical mixed models to investigate the associations between neural oscillations and pathology. We used a linear Neural‐Mass‐Model (NMM) in combination with empirical MEG spectra to derive the excitatory‐to‐inhibitory activity within neuronal subpopulations in AD patients. Based on standard neurophysiological monitoring we determined clinical evidence of hyperexcitability as AD with and without epileptiform activity (AD‐EPI+; AD‐EPI‐).ResultWhile increase and decrease of oscillatory activity are distinctly associated Aβ and tau, respectively, the characteristic frequency‐specific manifestation in AD was increased spectral signature within delta‐theta (2‐7Hz) and reduced spectral signature within alpha (8‐12Hz). Earliest spectral changes were detected in Aβ+ cognitively unimpaired and the increased spectral signature associated with Aβ was replicated in identical associations with plasma p‐tau181. The presence of APO‐E4 allele strengthened these associations. NMM demonstrated greater excitatory‐inhibitory‐activity in AD‐EPI+ vs. AD‐EPI‐ while these were specifically correlated with the reduced alpha spectrum which was more profound in AD‐EPI+ as well as uniquely associated with increased tau depositions.ConclusionOur results provide critical insights about potential mechanistic links between abnormal neural oscillations and cellular correlates of impaired excitatory and inhibitory synaptic functions associated with tau and Aβ, in patients with AD.
Noninvasive neuromodulation in Alzheimer’s disease: current status and future perspectives
Authors: Santarnecchi Emiliano 
Published: December 2023

AbstractBackgroundAlzheimer’s disease is a multifactorial disorder with multiple pathological substrates converging into clinical symptoms and cognitive deficits. Recent evidence suggests alterations of brain function beyond known pathways related to protein clearance, involving altered oscillatory activity in specific brain functional networks and alterations of synaptic plasticity within specific brain structures.MethodIn this context, the possibility to interact with cortical dynamics offered by noninvasive non‐pharmacological approaches pertaining to electrophysiology might open the way to a better understanding of the disease, and potentially lead to novel therapeutic interventions.ResultsIn particular, noninvasive brain stimulation techniques (NiBS) have gathered substantial interest in the study of dementia over the last decade, considered their promising value as diagnostic biomarkers of altered neural activity, as well as for their therapeutic potential of modulating network dysfunction and boosting residual cognitive functions.ConclusionAs part of the symposium, I will (i) review and discuss experimental NiBS applications in Alzheimer’s Disease (AD) and related dementias, including Transcranial Magnetic Stimulation (TMS) and transcranial Alternating Current Stimulation (tACS) interventions; (ii) provide an overview of multimodal TMS‐EEG perturbation‐based biomarkers for early diagnosis and monitoring, and (iii) discuss the potential of informing these applications via computational models mapping circuit‐level pathology in AD.
Associations between accelerometer‐based physical activity and brain white matter microstructure: Findings from the population‐based Rhineland Study
Authors: Fox Fabienne A.U. , Koch Alexandra , Breteler Monique M.B. , Aziz N. Ahmad 
Published: December 2023

AbstractBackgroundWhite matter (WM) integrity declines with age and is affected by neurodegenerative diseases. Physical activity promotes neuronal health in animals, and is associated with WM microstructure metrics in humans. However, previous diffusion tensor imaging (DTI) studies were limited by small sample sizes and subjective questionnaire‐based physical activity assessments. Moreover, recently introduced neurite orientation dispersion and density imaging (NODDI) may offer complementary insights. Therefore, we examined the association between accelerometer‐based physical activity and DTI and NODDI measures of WM microstructure in a large population‐based cohort.MethodWe analyzed data of 2,455 participants (57.9% women, mean age: 54.7 years) with valid physical activity and MRI measurements from the Rhineland Study, a prospective cohort study in Bonn, Germany. We recorded physical activity using accelerometers and derived metabolic equivalent (MET)‐hours, step counts and time spent performing sedentary, light‐intensity and moderate‐to‐vigorous (MVPA) activities. DTI (fractional anisotropy (FA), mean diffusivity) and NODDI (orientation dispersion index, neurite density index) measures were obtained from 3T MR images using the microstructure diffusion toolbox. The association of physical activity with WM microstructure was assessed using multivariate polynomial regression, while adjusting for age, sex, education, body mass index and smoking status.ResultPhysical activity was associated with several global and tract‐specific DTI and NODDI measures. Effects were strongest at low physical activity quantities and weakened at higher levels. While higher MET‐hours, step counts and light and moderate‐to‐vigorous intensity activities were related to greater global FA, sedentary time was associated with reduced FA. We observed the strongest tract‐specific effects for moderate‐to‐vigorous intensity activities on the corpus callosum and corona radiata (standardized effects: MVPA on FA corpus callosum, ßlin = 0.0009 [95% CI: 0.0001; 0.0018] and ßqu = ‐0.0006 [95% CI: ‐0.0011; ‐0.0001]; MVPA on FA corona radiata, ßlin = 0.0011 [95% CI: 0.0001; 0.0021] and ßqu = ‐0.0009 [95% CI: ‐0.0014; ‐0.0003]). We obtained similar results for NODDI measures.ConclusionOur findings suggest that WM microstructure and particularly tracts connecting motor regions profit from physical activity. Sedentary individuals may benefit more from additional physical activity than already active individuals. NODDI metrics provide valuable complementary insights into the effects of physical activity on WM microstructure.
Alzheimer’s Disease: Novel Findings, Challenges and Implications for Healthcare Systems
Authors: Uwishema Olivier 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a progressive, degenerative brain damage that impairs thinking and problem‐solving skills and causes memory loss as well as behavioural and emotional abnormalities. Amyloid plaques and tau tangles, aberrant protein clusters that cause cognitive deterioration, are the disease’s hallmark. The illness is a serious obstacle for the patient, their family, and caretakers, as well as for the healthcare system. This study aims to summarize the recent discoveries linking microorganisms and Alzheimer’s disease, the difficulties in confirming the theory, and suggestions on how scientists can improve alternative methods to study the underlying causes of AD.MethodAcademic publications were retrieved from the databases MEDLINE, Ebscohost, PubMed, Ovid, Embase, ScienceDirect, and Google Scholar using a unique search strategy. Emphasis was given to recent studies that provide insight into the current state, methods for diagnosis, and treatment options. Keywords in special combinations were used to retrieve information from various databases.ResultEvidence suggests that viruses can cause an increase in β‐amyloid peptide synthesis and tau phosphorylation, leading to the formation of senile plaques and neurofibrillary tangles. The absence of experimental evidence connecting microbes to the cognitive deficits and neuropathological alterations of AD, as well as the ambiguous composition and origin of the amyloids observed in senile plaques, are a few of the difficulties that researchers must overcome.ConclusionFurther research is pivotal in shaping the future of Alzheimer’s disease to fully comprehend the disease mechanism and treatment challenges. The development of tools to understand the complexity of the disease pathogenesis and its multifaceted aetiology is crucial. Additionally, in people who are predisposed to certain infections, early diagnosis of such infections may help delay the start of AD.