bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulating Effects of Vitamin K2 on Oxidative Stress Induced Organelle Damage in Alzheimer’s Disease
Authors: Shandilya Shruti , Ruokolainen Janne 
Published: December 2023

AbstractBackgroundCurrent treatment strategies for AD are either involved in an improved amyloid‐beta precursor protein (APP) processing via inhibition and/or activation of enzymatic machinery. Whereas, others drug regimen includes the use of putative tau kinase inhibitors, microtubule stabilizers and tau immunotherapies. Moreover, therapies to combat oxidative stress are currently being devised because oxidative stress plays a major role innneurodegeneration. Interestingly, current studies are being focused on the screening of bioactive compounds for their effect on prevention of Aβ formation, oxidative stress reduction and targeting organelle dysfunction, which will potentiate the use of bioactive compounds to prevent AD in early stages. Vitamin K2 is one of the bioactive compounds which has gained importance for its role as an antioxidant.MethodTo understand the neuroprotective effect of vitamin K2 during metabolic complications, SH‐SY5Y cells were treated with streptozotocin for 24 h and menadione for 2 h in a dose dependent manner, followed by the post treatment of vitamin K2 for 5 h. Modulating effects of vitamin K2 on cell viability, Lactate Dehydrogenase release, reactive oxygen species (ROS), mitochondrial membrane potential, ER stress marker (CHOP), an indicator of unfolded protein response (UPR) p‐IRE1α, GSK 3α/β, total tau and Aβ 42 were studied.ResultVitamin K2 significantly reduced the neuronal cell death by inhibiting the cytotoxicity, ROS levels and helped in the retainment of mitochondrial membrane potential. Moreover, vitamin K2 significantly decreased the expression of CHOP protein along with the levels and the nuclear localization of p‐IRE1 α, thus showing its significant role in inhibiting chronic ER stress mediated UPR and eventually apoptosis. In addition, Vitamin K2 significantly downregulated the expression of GSK 3 α/β together with the levels of total tau protein, with petite effect on secreted Aβ 42 levels.ConclusionVitamin K2 ameliorated mitochondrial damage, ER stress and tauopathy mediated neuronal cell death, highlighting its role as a novel antioxidative therapeutics targeting related cellular processes.
Spectral power ratio as a measure of the EEG spectral power shift in mild cognitive impairment due to Alzheimer’s disease
Authors: Flores‐Sandoval Aimee Arely , Davila‐Perez Paula , Buss Stephanie S. , Donohoe Kevin , O'Connor Margaret , Shafi Mouhsin , Pascual‐Leone Alvaro , Benwell Christopher , Fried Peter J. 
Published: December 2023

AbstractBackgroundMarkers sensitive to brain changes at the transition from mild cognitive impairment (MCI) to dementia due to Alzheimer’s disease (AD) are needed for aiding prognosis and the selection of potential responders to novel interventional therapies. EEG markers may be advantageous due to their accessibility.Prior research suggests that AD is associated with a shift in the brain’s oscillatory activity from higher to lower frequencies which can be captured as changes in the EEG spectral power ratio (SPR: α + β /δ + θ), a measurement associated with executive function1. The aim of the present study is to extend these findings to the prodromal stage of AD, and test the association of the SPR with amyloid burden.MethodData was obtained from 31 participants, including 23 aMCI (17 amyloid positive: Aβ+aMCI) and 14 CU individuals. We compared the SPRs between Aβ+aMCI and CU individuals, and tested its correlation with composite scores of executive functions, learning and memory, dementia severity, as well as amyloid load in the Aβ+aMCI group. Test‐retest reliability of the SPR was also inspected and the SPR of MCI individuals with different amyloid status was explored in hypothesis generating analyses.ResultThe SPR was significantly lower in the Aβ+aMCI group compared to the CU group (p = 0.0271) and was significantly correlated with Executive Function scores (r = 0.5634). The SPR showed excellent test‐retest reliability (rAβ+aMCI = 0.8629 and rCU = 0.9786). Logistic regression suggested that aMCI participants with a lower SPR had an increased probability of a positive amyloid PET.ConclusionOur results extended previous findings in AD and suggested that the SPR may be sensitive to pathophysiological changes in aMCI individuals in a cognitively meaningful manner. Further research may confirm these findings and may explore the potential of this measure to aid in the classification of aMCI individuals according to their amyloid status.1. Benwell CSY, Davila‐Pérez P, Fried PJ, Jones RN, Travison TG, Santarnecchi E, Pascual‐Leone A, Shafi MM (2020) EEG spectral power abnormalities and their relationship with cognitive dysfunction in patients with Alzheimer’s disease and type 2 diabetes. Neurobiol Aging
85, 83‐95.
Clustering of neuropsychiatric symptoms across time in Alzheimer’s disease and Mild Cognitive Impairment
Authors: Scarfo Sara , McGeown William J , Moshfeghi Yashar 
Published: December 2023

AbstractBackgroundNeuropsychiatric symptoms are behavioural manifestations highly prevalent along the Alzheimer’s disease (AD) continuum, including at the stage of Mild Cognitive Impairment (MCI). Although various projects have investigated the factors that underpin these symptoms, the most stable clustering pattern is still matter for debate; furthermore, to our knowledge, no study has investigated, longitudinally, how clusters might change due to development of AD pathology. Therefore, our objective is to investigate neuropsychiatric clusters over time, in a large sample of MCI and AD dementia patients.MethodsSamples were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu), using data from the Neuropsychiatric Inventory (NPI), from the baseline assessment visit, followed up yearly until data recorded at month 72. The samples included MCI and AD dementia patients (based on ADNI’s inclusion criteria), presenting with at least one neuropsychiatric symptom at the time‐point selected. Using SPSS (Version 28), we performed a series of exploratory principal components analyses (PCA), Varimax rotation, and principal axis factor analyses (FA), comparing Promax and Direct Oblimin rotations.ResultsThe best‐fitting structure was interpreted at each time‐point, based on: Eigenvalues>1, items’ loadings>0.4, scree plot patterns, minimum 40% of variance explained by the model, and independence of factors. Results from both PCA and FA indicated that a unique structure could not be identified, as factors were not stable over time; however, some symptoms tended to load on the same factors across most measurements (i.e. delusions with hallucinations; agitation with depression, anxiety and irritability; to a lesser extent elation with disinhibition; apathy with aberrant motor behaviour, sleep disturbances and appetite disorder).ConclusionsThe available evidence reveals that factors underlying the neuropsychiatric symptoms in a sample of AD and MCI patients are not consistent across the time‐points. However, some symptoms tend to co‐occur across time, with implications, for example, that an investigation into one of those symptoms should consider the presence of the other; furthermore, as clear theoretically driven factors are not distinctively identified at every time‐point, this illustrates the potential importance of sample selection (e.g., disease stage, and/or heterogeneity) on studies of neuropsychiatric symptoms.
Value of Knowing following Amyloid PET Results Disclosure in Mild Cognitive Impairment
Authors: Wang Yan A , Ren Dianxu , Roberts J. Scott , Lingler Jennifer H 
Published: December 2023

AbstractBackgroundPersonal utility is commonly cited as a rationale for Alzheimer’s disease (AD) biomarker testing. Yet, limited reports document how the value of knowing one’s AD biomarker status manifests in cognitively symptomatic patients. Emerging literature suggests two potential dimensions to the construct: a) inherent value, or “knowledge for the sake of knowledge,” and b) value of knowing as a basis for action. We describe actions taken by patients following amyloid PET results disclosure with the goal of elucidating the value of knowing AD biomarker status in cognitively symptomatic populations.MethodWe analyzed longitudinal health behavior assessments completed by patients with mild cognitive impairment who learned of being amyloid positive (n = 12), negative (n = 22), or assigned to a comparison group (n = 37). Patients were 92% non‐Hispanic white, 59% male, 73±8.61 years old with 16.25±2.49 years of education. Qualitative interviews supplemented scan group participants’ data. Both questionnaires and qualitative interviews focused on activities newly adopted to promote cognitive health or plan ahead.ResultOver 12 months of follow‐up, all participants reported at least one behavior change from baseline. Amyloid positive patients reported the most behavior changes (mean = 4.67/14±1.83) while amyloid negative patients reported the fewest (mean = 3.72±1.58). Across groups, no significant differences were observed in changes to: lifestyle, vitamin/supplement use, stress reduction activities, cognitive stimulation, and advance directive completion. Amyloid negative participants were significantly less likely than controls to consider long‐term care insurance (63.6% vs. 89.2%; P = .025), and to endorse changes classified as “other” (36.4% vs. 64.9%; P = 0.037). After adjusting for education level, gender, and MMSE, logistic regression showed that amyloid negative patients were 74% less likely than controls to report “other” changes (OR = 0.26, 95% CI [0.08, 0.85], P = 0.025), and 78% less likely to consider long‐term care insurance (OR = 0.22, 95% CI [0.06, 0.86], P = 0.03). Qualitative analysis yielded insight into “other” activities, including changes in employment, driving, and residential status, and engagement in other non‐medical activities (pursuing bucket list activities and mending strained relationships), particularly among amyloid positive patients.ConclusionValue of knowing one’s amyloid status may differ by scan result and encompass a wide range of actions to enhance not only cognition but quality of life.
Beyond psychological well‐being and behavior change: Participant experience and evaluation of an AD biomarker disclosure and lifestyle counseling protocol
Authors: Erickson Claire M , Basche Kristin E , Chin Nathaniel A. , Ketchum Fred B , Clark Lindsay R. 
Published: December 2023

AbstractBackgroundEarlier detection and improved accessibility of testing means more adults may learn their Alzheimer’s biomarker results. Incorporating feedback from individuals who have learned their results is important to improve disclosure protocols and individual outcomes.MethodParticipants (n = 97,age = 71.9±4.8) from the Wisconsin Registry for Alzheimer’s Prevention study enrolled in a disclosure study consisting of an education session, amyloid PET results disclosure, and lifestyle counseling visit. Participants reported their visit satisfaction and provided feedback for improvement. Upon study completion, participants evaluated various study procedures (e.g., understanding of the results, regret in learning result, etc.). Chi‐square analyses and response distributions were computed to compare participants with an elevated and non‐elevated amyloid result.ResultNo statistically significant differences in disclosure or lifestyle visit satisfaction were found between participants with an elevated and non‐elevated amyloid PET result. Overall, 95% of participants reported that the disclosure visit was “somewhat” or “very” useful. 70% of participants endorsed the usefulness of the lifestyle counseling visit. 100% and 81% of participants recommended we continue disclosure and lifestyle counseling visits, respectively. For the disclosure visit, both groups suggested we provide more information on the amyloid result (e.g., provide scans, risk, etc.), offer an in‐person, face‐to‐face visit, and reduce the number of questions assessing suicidal ideation. Elevated participants suggested allowing a loved one to join the visit. Feedback on the lifestyle counseling visit included more accountability check‐ins and providing a more personalized discussion. On study evaluation measures, groups differed on the reported usefulness of educational materials (χ2(2,n = 87) = 6.42,p = .04) and regret in learning results (χ2(2, n = 87) = 10.7,p = .005). While no participants regretted learning their results, elevated participants were more likely to respond “neutral” (15% vs 0%), whereas non‐elevated participants were more likely to respond “strongly disagree” (74% vs. 54%) to regretting learning their result. There were no group differences on understanding or usefulness of result.ConclusionWe found very limited differences between elevated and non‐elevated participants on satisfaction and evaluation of learning amyloid PET results. It remains important to offer follow‐up, especially for elevated participants, who may need extra support post‐disclosure. Ultimately, most participants found the study visits worthwhile and found learning their result useful.
Tau‐PET to predict conversion from mild cognitive impairment to dementia; a head‐to‐head comparison against amyloid‐PET and MRI
Authors: Groot Colin , Smith Ruben , Collij Lyduine E. , Mastenbroek Sophie E , Stomrud Erik , Binette Alexa Pichet , Leuzy Antoine , Palmqvist Sebastian , Mattsson‐Carlgren Niklas , Strandberg Olof , Ossenkoppele Rik , Hansson Oskar 
Published: December 2023

AbstractBackgroundIn contrast to amyloid‐PET and MRI, tau‐PET imaging has not been integrated into clinical practice even though it shows a close relationship with clinical symptoms. With the present study, we aim to assess the performance of tau‐PET to predict conversion to dementia (all‐cause and AD) in individuals with mild cognitive impairment (MCI), and compare it with amyloid‐PET and MRI.MethodWe selected participants from an ongoing multicenter study (n = 408, Table 1). The following ROIs were used to define quantified thresholds for positivity using an independent cognitively unimpaired reference group: a temporal meta‐region for tau‐PET and an AD‐susceptible temporoparietal region for MRI‐based cortical thickness. For amyloid‐PET, we used the standard Centiloid mask and a published threshold of 27 Centiloids to determine positivity. We additionally performed visual reads for all imaging modalities. We used Cox proportional hazard, logistic regression, and receiver operating curve (ROC) analyses to assess the performance of amyloid‐PET (A), tau‐PET (T), and MRI (N) to predict progression from MCI to dementia over a mean follow‐up period of 2 years.ResultHazard ratios indicated that tau‐PET and amyloid‐PET positivity (both when assessed quantitatively and using visual reads) conveyed a greater risk of progression to dementia than MRI, and that a combination of A+ and T+ (or N+) conveyed a greater risk than A‐T‐N‐ or isolated A+ or T+ (Figure 1). ROC analyses revealed that only tau‐PET performed better than demographics alone when predicting all‐cause dementia while both amyloid‐ and tau‐PET performed better than demographics and MRI when predicting AD dementia. LASSO logistic regression revealed that the optimal model to predict conversion from MCI to all‐cause dementia included a quantitative MRI marker and tau‐PET visual read. For optimal prediction of AD dementia specifically, the quantitative measure of amyloid‐PET was added in addition to the quantitative MRI marker and the tau‐PET visual read (Table 2).ConclusionAmong individuals with MCI, tau‐PET performs best when predicting dementia, and can be optimized when combined with MRI. For AD dementia, tau‐PET and amyloid‐PET are the best‐performing modalities, but an optimal prediction is again achieved when combined with MRI.
Impact of sharing Alzheimer’s disease biomarker results with individuals without dementia: a systematic review and meta‐analysis of empirical data
Authors: van der Schaar Jetske , Visser Leonie N.C. , Ket Johannes C.F. , Groot Colin , Pijnenburg Yolande A.L. , Scheltens Philip , Bredenoord Annelien L. , Hoven Mariette A. , van der Flier Wiesje M. 
Published: December 2023

AbstractBackgroundA biological definition of Alzheimer’s disease (AD) is increasingly used in research, but little is known about the consequences of early biomarker testing from the perspective of professional (healthcare professionals) and personal (citizens, patients, and their families) stakeholders. We aim to provide a systematic literature review and meta‐analysis of empirical evidence on expected and experienced implications of sharing AD biomarker results with individuals without dementia.MethodWe searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection on 10 November 2021 for literature on sharing AD biomarker results with individuals without dementia. Two reviewers independently screened 8034 titles and abstracts, and 192 full‐text records, for eligibility. Results from included studies were synthesized and quantitative data on psychosocial impact (anxiety, depression, stress, and suicidal ideation) were meta‐analyzed using a random‐effects model.ResultWe included 33 publications (20 quantitative and 13 qualitative data). Of these, eight reported on professional stakeholders’ attitudes and practices, 13 on personal stakeholders’ expectations, and 12 on their actual experiences. Most professional stakeholders valued biomarker testing, believing the benefits outweigh the risks, although attitudes and practices varied considerably. Most personal stakeholders expressed interest in (hypothetical) biomarker assessment, expecting to gain insight, reduce dementia risk and prepare for the future. Studies evaluating actual experiences found that sharing negative biomarker results led to relief and sometimes frustration for not having an explanation for concerns, while positive biomarkers prompted anxiety but also clarity. Those tested positive intended to adapt their lifestyle and plans, yet some worried about stigmatization. The majority did not regret being informed. Meta‐analysis of 5 studies including 2012 participants (elevated amyloid = 1324, asymptomatic = 1855) showed that short‐term psychological impact was not significant when considering all participants (random‐effect estimate = 0.026, SE = 0.018, p = 0.153), nor biomarker‐positive (estimate = 0.012, SE = 0.019, p = 0.538), or biomarker‐negative individuals (estimate = 0.061, SE = 0.043, p = 0.154) separately.ConclusionMost personal stakeholders indicate they wish to know their AD biomarker status. While sharing results could induce mixed emotions, it does not cause short‐term psychological harm and may offer actionability. There is a need for developing and harmonizing guidelines for biomarker testing and sharing results, particularly in view of the imminent advancements in disease‐modifying treatment.
Time‐encoded ASL shows higher sensitivity to detect cerebral blood flow reductions in AD
Authors: Falcon Carles , Montesinos Paula , Vaclavu Lena , Minguillon Carolina , Fauria Karine , Suarez‐Calvet Marc , Grau‐Rivera Oriol , Puig‐Pijoan Albert , Cascales‐Lahoz Diego , Contador José , Fernández‐Lebrero Aida , Navalpotro Irene , Van Osch Matthias J.P. , Sanchez‐Gonzalez Javier , Gispert Juan Domingo 
Published: December 2023

AbstractBackgroundPseudo continuous arterial spin labelling (pcASL) is an MRI technique to quantify cerebral blood flow (CBF). Time encoded ASL (te‐ASL) is a multiple time‐point pcASL variant that by acquiring several post‐label delays (PLD) to have more accurate CBF estimation allowing to measure arterial‐transit time (ATT). The aim of this study was to assess the performance of te‐ASL in detecting CBF and ATT changes in the Alzheimer’s disease (AD) continuum.MethodThe sample consisted of 59 subjects: 25 healthy controls (HC), 17 cognitively unimpaired individuals with positive cerebrospinal fluid (CSF) biomarkers (Ab42<1.098pg/mL; p‐Tau181>19pg/mL; Elecsys® ‐Roche Diagnostics) (preAD) and 17 patients with clinical diagnosis of AD (Ab42/p‐Tau181 ratio <10.25; Lumipulse‐Fujirebio). The MRI protocol comprised of anatomical T1, and ASL sequences (M0 and te‐ASL). CBF and ATT maps were calculated in the oxford_asl toolbox in FSL. CBF and ATT maps were spatially normalized to the MNI, smoothed (12mm FWHM) and intensity normalized to the cerebellar gray matter. To detect patterns of lower CBF, voxel‐wise one way 3‐group ANOVA and post‐hoc paired t‐tests were performed using age and sex as confounders (SPM12; statistical threshold: p<0.001 uncorrected; k>100 voxels (∼0.33cm3) in all analyses). We compared results with those obtained using a single PLD by computing CBF from the last PLD (perfusion block, nominal PLD time of 2000ms) of the te‐ASL schema.ResultTable 1 displays the descriptive statistics of the sample. Figure 1 shows that, with te‐ASL, AD patients displayed lower CBF (yellow) in extensive bilateral pareto‐temporal, cingulate and occipital areas. Preclinical AD participants showed an overlapping pattern (green), albeit reduced in extension. When using pcASL, the detected pattern of lower CBF in the AD group was less extended and did not overlap with that of the PreAD groups. No ATT differences were found associated to AD.Conclusionte‐ASL was more sensitive to detect CBF differences across the AD continuum than single PLD ASL. The pattern of lower CBF in the AD group covered expected areas, and that in the preclinical AD group partially overlapped.