bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home‐Based Multifocal Brain Circuit‐Based Neuromodulation Combining tACS and tDCS in Older Adults with Alzheimer’s Disease
Authors: Gilfix Talia , Zheng Judy , Davis Jonathan , Fox Rachel , Stein Benjamin , Yu Wanting , Morgan Jasmine , Syed Alisha , Syme Maggie L , Opitz Alexander , Manor Bradley , Pascual‐Leone Alvaro , Cappon Davide 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) affects over 55 million people worldwide and is characterized by abnormal deposition of amyloid‐β and tau in the brain causing neuronal damage and disrupting transmission within brain circuits. Episodic memory loss, executive deficits, and depression are common symptoms arising from altered function in spatially distinct brain circuits that greatly contribute to disability. Transcranial electrical stimulation (tES) can target these circuits and has shown promise to relieve specific symptoms. However, previous trials focused on a single symptom and have been limited by poor quantification of induced electric fields (E‐field) in the intended cortical target(s). The studies aim to provide multi‐symptom relief to older adults with AD by combining two types of tES.MethodFourteen participants diagnosed with mild cognitive impairment (MCI) or early dementia due to AD were recruited as part of two studies (Table 1). Optimization of tES was performed by modeling the normal component of the induced E‐field (En) to target the left dorsolateral prefrontal cortex (DLPFC, Brodmann area 46) with transcranial direct current stimulation (tDCS) and to target the left angular gyrus (AG, Brodmann areas 39/40) with transcranial alternating current stimulation (tACS – 40 Hz) (Figure 1). Participants received daily stimulation sessions for four weeks at home, with baseline, post‐intervention, and 3‐month follow‐up assessments. E‐field modeling using MRIs evaluates behavioral effects' dependency on E‐field induced by tDCS and tACS in DLPFC and AG.ResultBoth studies showed excellent adherence to a home‐based, multi‐symptom tDCS/tACS intervention. To date, out of 280 scheduled sessions across 14 participants, 278 were completed, with a 99% adherence rate. The most common side effects were mild and transient (Table 2). Structural MRI scans were used to quantify E‐field modeling in target brain regions.ConclusionThe studies demonstrate the safety, feasibility, and adherence of a remote‐supervised, caregiver‐led home‐based intervention combining tDCS and tACS to target two distinct brain networks and thus induce a more meaningful clinical impact by reducing distinct disabilities in AD. Quantifying the induced E‐field will provide data to assess the mediating effects of E‐field on treatment outcomes, yielding critical insights to enable future larger‐scale trials.
All‐cause mortality among veterans with mild cognitive impairment and Alzheimer’s dementia who have Intracerebral hemorrhage and subarachnoid hemorrhage
Authors: Aguilar Byron J. , Wang Ying , Arasa Vanesa Carlota Andreu , Berlowitz Dan , Mittler Brant , Morin Peter J , Reisman Joel , Abdennadher Myriam , Querfurth Henry W , Zhang Raymond , Monfared Amir Abbas Tahami , Zhang Quanwu , Xia Weiming , Aguilar Byron J. 
Published: January 2025

AbstractBackgroundCerebral amyloid angiopathy (CAA) is a significant contributor to hemorrhagic stroke, notably lobar intracerebral hemorrhage (ICH) and convexity subarachnoid hemorrhage (SAH), both of which have been observed in patients with MCI/AD. To evaluate all‐cause mortality among veterans with mild cognitive impairment (MCI) and Alzheimer’s dementia (AD) with/without Intracerebral hemorrhage and subarachnoid hemorrhage (ICH/SAH) in the United States (US) Veterans Affairs Healthcare System (VAHS).MethodVeterans with MCI or AD were identified based on having clinical notes or diagnostic codes in the VAHS database (2010‐2019). ICH and SAH were identified with ICD‐10 codes I61.x and I60.x, respectively. Survival curves were generated, and Poisson regression was used to adjust for baseline characteristics.ResultA total of 853,791 veterans with MCI/AD were included, with a mean age of 74 years, of which 96% were male, 5% Hispanic, 15% Black, and 74% White; 32% had MCI and 68% had AD. Approximately 0.6% of the overall sample had ICH/SAH. The observed mortality rates per 1000 person‐years were 130 for males and 60 for females and 138 for AD vs 102 for MCI. Mortality rates for Veterans with MCI/AD with and without ICH was 102 and 127, and with and without SAH was 83 and 127, respectively. Kaplan‐Meier curves showed a higher survival probability for Veterans with ICH/SAH events vs those without the events (P<0.01) and for AD vs MCI (P< 0.01; Figure). The mortality risk was lower for MCI than AD overall (IRR = 0.83, P< 0.01). The death rate in veterans with MCI/AD was statistically significantly lower for those with vs without ICH/SAH even after adjustment (IRR = 0.85, p<0.01). Death rate was higher in non‐Hispanic vs Hispanic (IRR = 1.23, P<0.01) and for White vs Black veterans (IRR = 1.05, P<0.01).ConclusionIn US VAHS, AD was associated with an increased risk of death than MCI; ICH/SAH did not increase mortality risk. After adjustment, mortality rates were found to be 23% higher for non‐Hispanic vs Hispanic groups and 5% higher for White vs Black groups. Those findings will be further examined by incorporating Medicare data for Veterans who had dual eligibility for both VA and Medicare coverage.
Health‐related Quality of Life in People living with Dementia – Over and Underestimation of Proxy‐ratings
Authors: Buchholz Maresa , Engel Lidia , Weber Niklas , Michalowsky Bernhard 
Published: January 2025

AbstractBackgroundProxy ratings primarily provided by informal caregivers are usually administered if patients living with dementia (PlwD) are cognitively unable to rate health independently. The literature is limited by the use of typically agreement statistics, reporting that proxies generally underestimate PlwD health. Additional analyses of self‐ and proxy‐rated discrepancies in individual responses that focus on HRQoL dimensions are lacking. We examined discrepancies between self‐ and proxy‐rated health in PlwD on an individual response level.MethodWe analyzed baseline data of n = 174 dyads (PlwD and their caregivers) of a cluster‐randomized, controlled intervention trial. HRQoL was assessed with the EQ‐5D‐5L from a self‐ and proxy‐proxy perspective together with sociodemographic and clinical data. The EQ‐5D‐5L consists of five dimensions (“mobility”, “self‐care”, “usual activity”, “pain/discomfort”, “anxiety/depression”), each with five response options. Initially, we calculated agreement statistics (weighted kappa) for each dimension. For individual response levels, we analyzed the degree of inconsistencies between self‐ and proxy ratings ranging from 0 (identical responses in all dimensions) to 5 (different responses in all five dimensions). We grouped the PlwD into “no problems” and “problems” depending on the EQ‐5D‐5L response of each dimensions to compare the response distances between PlwD and caregivers.ResultPlwD had a mean age of 80.1 years (49.1% female) with a MMSE mean score of 19.2; informal caregivers were, on average, 67.9 years old (67.8% female). Every third PlwD lived alone. In general, PlwD rated their HRQoL better than proxies (EQ‐5D‐5L indices: 0.75±0.25 vs 0.68±0.23; p<0.01). Nine dyads (5%) showed identical ratings, whereas 95% rated their health differently. Weighted kappa coefficients were lowest for the dimension usual activity (0.23) and highest for pain/discomfort (0.40). Among the grouped PlwD without and with problems, proxies estimated PlwD HRQoL worse (underestimation) or better (overestimation), respectively. This was due to a central‐tendency‐bias of caregivers, two times more frequently selecting mid‐response options, particularly apparent in mobility, usual activities, and self‐care.ConclusionThe two trends of contrary response behaviour (over‐ and underestimation & central tendency bias) could be caused by uncertainties of caregivers, underlining the challenge of using both perspectives interchangeably. Further research is needed when using HRQoL measures as proxy instruments.
Worry differentially affects the impact of placental growth factor on processing speed in older adults with amnestic Mild Cognitive Impairment
Authors: Lam Jovian C , Savettiere Adriana , Louras Peter , Fairchild Jennifer Kaci 
Published: January 2025

AbstractBackgroundPlacental growth factor (PIGF) is an angiogenic, pro‐inflammatory biomarker that is overexpressed in cardiovascular diseases. Recent literature has linked PIGF to the identification of cognitive impairment with white matter burden. Worry is associated with an increased risk for cardiovascular disease, accelerated aging and subsequent reduced brain volume, and decline in cognition. Given these associations, worry presents as a potential link to PIGF and cognitive impairments, though no research to date has examined its relationship to PIGF and cognition. Thus, current study aims to examine the possible moderating role of worry on PIGF and cognitive function (e.g., processing speed) in older adults with amnestic mild cognitive impairment (aMCI).MethodParticipants included sixty‐six community‐dwelling older Veterans (Mage = 70.97 ± 8.66 years) who met criteria for aMCI. The sample was primarily male (95%), White (74%), and well‐educated (56% with bachelors or above). Composite scores reflective of processing speed were created using participants’ performances on the following measures: Symbol Digit Modalities Test, Stroop Color and Word subtests, and Trail Making Test A. Worry was measured by the Penn State Worry Questionnaire. Plasma PIGF levels were analyzed using SomaScan® disease‐specific panels. Hierarchical linear regressions were used to examine the moderating effect of worry on the relationship between PIGF and processing speed, while controlling for age.ResultResults indicated an overall significant model F(4,61) = 8.28, p < .01, ΔR2 = .03 and main effect of PIGF (β = ‐2.12e‐03, t = ‐2.28, p = .03) on processing speed. There was also a significant interaction between worry and PIGF (β = ‐1.30e‐04, t = ‐2.02, p < .05). Follow‐up analyses indicated a significant association between PIGF and processing speed in individuals with higher levels (+ 1 SD) of worry (β = ‐.01, t = ‐3.34, p < .01).ConclusionThe current results present a novel finding that worry intensifies the inverse relationship of PIGF and processing speed. Importantly, the current study reinforces a biopsychological link to cognition and a more nuanced consideration when examining biomarkers and risk factors of cognitive impairment.
Perivascular Space Analysis: A Possible Tool for Predicting Cerebral Amyloid Angiopathy in Pathology‐Confirmed Cases
Authors: Fotouhi Maryam , Sheikh‐Bahaei Nasim , Choupan Jeiran 
Published: January 2025

AbstractBackgroundDiagnosis of cerebral amyloid angiopathy (CAA) presents a significant challenge in determining whether to propose anti‐amyloid treatment plans. The identification of perivascular spaces (PVS) through MRI serves as a possible strategy to elucidate the physiopathological interconnections between the brain's clearance mechanisms and the accumulation of amyloid. This study endeavors to the association between PVS morphology and CAA pathology.MethodsT1‐weighted and T2‐FLAIR MRI data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Demographic details (sex, age, post‐mortem interval) and ADNI pathologic scores were gathered. Histological images provided scores for cerebral amyloid angiopathy. Leveraging our on the last premortem MRI, we automatically mapped regional PVS in white matter and basal ganglia. analysis was then employed to investigate whether premortem regional PVS volume fractions serve as predictors for postmortem CAA pathology, accounting for age, sex, and post‐mortem interval.ResultsThe investigation revealed notable predictive associations between specific occipital regions' PVS volume fractions and the presence of amyloid angiopathy pathology, after multiple comparison correction. Specifically, the study identified the right cuneus PVS volume fraction as a robust predictor for the manifestation of amyloid angiopathy pathology (t=3.12, p=0.001). Similarly, the left precuneus PVS volume fraction emerged as a statistically significant predictor (t=2.78, p=0.005).ConclusionThis study presents a noteworthy advancement in amyloid angiopathy diagnosis, employing standard MRI analysis of perivascular spaces. The identified correlation offers a pragmatic means to enhance diagnostic accuracy without complexity. This research underscores the potential applicability of PVS analysis in routine clinical practice for early CAA detection, contributing significantly to the practical improvement of CAA diagnostics.Reference: 1. Sepehrband, F., Barisano, G., Sheikh‐Bahaei, N. et al. Image processing approaches to enhance perivascular space visibility and quantification using MRI. Sci Rep 9, 12351 (2019). https://doi.org/10.1038/s41598‐019‐48910‐x
Reducing Pre‐screening Cognitive Assessment Variability to improve Enrollment in clinical trials
Authors: Toll Nicholas 
Published: January 2025

AbstractBackgroundA standard practice at our research site has been the administration by a clinician of cognitive pre‐screeners to the subjects in our initial visit. The administration of these assessments, along with the examination of medical histories, is designed to evaluate a patient’s current cognitive abilities and assist with their placement in the most appropriate study. However, as the number of clinicians increased, variation regarding administration of the cognitive screener was noted, resulting in a likelihood of increased rate of screen failures.MethodTo reduce the rate of screen failures at our research site and to increase the specificity of pre‐screening we implemented an improvement process to have one trained individual administering all of the standard cognitive pre‐screenings.ResultThis design resulted in a 25% reduction of outcomes variability due to multiple examiners, as unique responses are more likely to be interpreted in a similar manner. The methodology reduced practice effects as cognitive screening questions may be inadvertently discussed prior to the screener (e.g., month, date, place) during interview with the subject and caregiver. Additionally, the process eliminates any potential for relationship bias, as the trained individual has no prior relationship to the subject, as well as assist the clinician in tailoring the interview to specific qualifying studies.ConclusionThe improvement process reduced the number of screen failure allowing our site to take another step in the long and difficult collaborative process involved with the creation and approval of novel medications.
Developing a novel claim‐based algorithm to identify incident and prevalent dementia using Medicare claims of the Atherosclerosis Risk in Communities (ARIC) cohort
Authors: Wang Tiansheng , Pate Virginia , Kim Dae , Power Melinda C , Garden Gwenn A , Palta Priya , Knopman David S. , Jonson‐Funk Michelle , Stürmer Til , Kucharska‐Newton Anna M. 
Published: January 2025

AbstractBackgroundPharmacoepidemiologic studies assessing drug effectiveness for Alzheimer’s disease and related dementias (ADRD) are increasingly popular given the critical need for effective therapies for ADRD. To meet the urgent need for robust dementia ascertainment from real‐world data, we aimed to develop a novel algorithm for identifying incident and prevalent dementia in claims.MethodWe developed algorithm candidates by different timing/frequency of dementia diagnosis/treatment to identify dementia from inpatient/outpatient/prescription claims for 6,515 and 3,997 participants from Visits 5 (2011‐2013; mean age 75.8 (SD 5.3) years) and 6 (2016‐2017; mean age 79.8 (SD 4.8) years) of the ARIC cohort with ≥ 1‐year continuous Medicare Part A & B enrollment prior to each visit. We evaluated algorithm performance (sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV)) against the gold standard of the ARIC dementia classification based on an extensive battery of neurocognitive tests administered at each visit. We compared performance of the new algorithm with that of three existing algorithms (Jain, Bynum, Lee) and their relaxed forms (4‐year window, dementia diagnosis plus a depression diagnosis or dementia evaluation procedure, ignoring code position) to identify incident (n = 90 at V6) and prevalent dementia (n = 190 at V5; n = 160 at V6).ResultThe newly developed primary algorithm requires presence of a dementia diagnosis code followed by another diagnosis code within 1 year (under condition that the following non‐specific ICD‐9 diagnostic codes, 290.40, 290.41, 290.11, 290.3, should appear no more than once), or a subsequent dementia treatment prescription within 90 days (requiring Medicare Part D enrollment ≥ 6 months). The PPV of the new algorithm in the identification of incident dementia was PPV of 72.7%, with a specificity of 99.1%, outperforming existing algorithms. Its sensitivity of 38.7% and NPV of 96.2% were comparable to those achieved by existing algorithms. Sensitivity analysis restricting to ICD‐10 diagnostic codes increased the PPV and attenuated its sensitivity by 6%. Similar comparative performance was observed in the identification of prevalent dementia.ConclusionA novel algorithm for identifying dementia from Medicare claims, developed using linked ARIC‐Medicare data, outperforms previous algorithms and stands as a valuable tool in the assessment of ADRD drugs from real‐world data.
Psychometric properties of the Psychological Consequences of Screening Questionnaire (PCQ) adapted for cognitive screening
Authors: Lovett Rebecca , Filec Sarah , Hurtado Jeimmy , Kwasny Mary , Sideman Alissa Bernstein , Persell Stephen , Possin Katherine L , Wolf Michael S 
Published: January 2025

AbstractBackgroundContext‐specific measures with high content validity are needed to adequately determine psychosocial effects related to screening for cognitive impairment. The objective of this investigation was to examine psychometric properties of the Psychological Consequences of Screening Questionnaire (PCQ), a measure of psychological impact of medical screening, adapted for cognitive screening in primary care.MethodsTwo‐hundred adults aged ≥65 recently completing routine, standardized cognitive screening as part of their Medicare Annual Wellness Visit were administered the adapted PCQ measure, comprised of negative (PCQ‐Neg) and positive (PCQ‐Pos) scales. Measure distribution, acceptability, internal consistency, factor structure, and content validity (construct, discriminative, criterion) were analyzed.ResultsParticipants had a mean age of 73.3, were primarily female and socioeconomically advantaged. Nearly all received a normal cognitive screening result (99.5%). Overall PCQ scores were low (PCQ‐Neg: M 1.27; PCQ‐Pos: M 7.63). Both scales demonstrated floor effects. Acceptability was satisfactory, although the PCQ‐Pos had slightly more item missingness. Both scales had Cronbach alpha’s >0.80 and a single factor structure. Spearman correlations between the PCQ‐Neg with general measures of psychological distress ranged from 0.26 to 0.37 (p’s <0.001); correlation with a measure of well‐being was ‐0.19 (p<0.01). The PCQ‐Neg discriminated between those with and without a subjective cognitive complaint (M 2.73 vs. 0.89, p <0.001), and was associated with medical visit satisfaction (r = ‐0.24, p<0.001). The PCQ‐Pos predicted willingness for future screening (M 8.00 vs 3.00, p = 0.03).ConclusionsThe adapted PCQ‐Neg scale is an overall valid measure of negative psychological consequences of cognitive screening; findings for the PCQ‐Pos scale were more variable. Future studies are needed to further understand PCQ performance among more diverse samples and those with abnormal test results following cognitive screening.
The interaction between dietary habits, BDNF, CCK, and gut microbiota in the pathophysiology of Alzheimer’s disease
Authors: Montgomery Caitlin E , Hipsley Jessica Arango , Schuh Olivia , Shah Anjali , Khanna Deepesh 
Published: January 2025

AbstractBackgroundResearch heavily suggests that brain‐derived neurotrophic factor (BDNF), vital for neuronal growth and plasticity, and cholecystokinin (CCK), a satiety hormone that regulates BDNF levels, are altered in Alzheimer’s Disease pathophysiology. Factors such as dysbiosis of gut microbiota and poor food habits may affect CCK and BDNF release and brain function. The objective is to evaluate the effects of dietary habits, gut microbiota, and exercise on BDNF and CCK release in Alzheimer’s Disease patients.MethodsA comprehensive review on how BDNF and CCK levels are affected in Alzheimer’s patients was conducted using databases like PubMed and Google Scholar. Search string keywords included “Alzheimer’s,” “BDNF,” “CCK,” paired with “exercise,” “diet,” and “gut microbiota.” The inclusion criteria included original articles published from 2012‐2024 from peer‐reviewed journals and studies exploring CCK and BDNF interaction with diet, exercise, and gut microbiota. Eligible studies were excluded if BDNF and CCK levels were associated with diseases other than Alzheimer’s. Papers were not restricted to the US population.ResultsLiterature suggests BDNF levels significantly increase with exercise in Alzheimer’s disease patients. BDNF levels decrease in mice fed a high‐fat diet that reflects the Western diet. Research on the connection between gut microbiota and Alzheimer’s disease has also been explored in human and mice studies. A study conducted on human participants showed serum BDNF levels to significantly increase at Week 12 in the probiotic’s treatment group in contrast to the placebo group (−3.32 ± 2.35 ng/mL). A study on healthy mice that were given fecal microbiota transplantation from 5XFAD mice with major features of Alzheimer’s Disease amyloid pathology demonstrated elevated proinflammatory cytokines and decreased neurogenesis in the brain. Studies exploring CCK levels found that higher CCK was significantly associated with greater gray matter volume in areas of the brain that play a role in memory primarily spanning cingulate cortex and parahippocampal gyrus. In Alzheimer’s patients, CCK levels were found to be significantly lower.ConclusionFindings collectively suggest the complex interactions between diet, exercise, and neurocognitive outcomes, with both dietary interventions and physical activity, positively influence synaptic plasticity, cognitive performance, and biomarkers associated with neurodegenerative diseases.