bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alzheimer’s disease treatment with Transcranial Pulse Stimulation using shockwave pulses is increasingly successful: Patient’s feedback is very positive
Authors: Novak Pavel 
Published: December 2022

AbstractBackgroundDue to the aging world population is the number of patients suffering from dementia continuosly increasing. There are currnently worldwide 46.8Mio. cases, the estimation for 2050 are 131.5Mio. Most common cause of dementia is the Alzheimer’s disease, which is curently uncurable. It is a progressive neurologic disorder that causes brain cells to die and the brain to shrink.MethodShockwaves are used in medicine since 1980. Starting with kidney stone disintegration, low intensity shockwaves are used for soft tissue stimulation since 1990. Mechanical stimulation of biological processes by shockwaves called mechanotransduction results in increased cell metabolism, release of nitric oxide and numerous growth factors, as VEGF and BDNF. There is also an anti‐inflammatory effect, stimulation of stem cells and of the innate immune system. The treatment of pain and spasm were the first neurological shockwaves applications. In 2004, first patients with spinal cord injury were treated. In parallel, the scientific investigations demonstrated that shockwaves not only stimulate, but also regenerate the nerves after lesions. Finally, since 2010 followed the brain treatment of patients with unresponsive wakefulness, Parkinson’s and Alzheimer’s disease. Alzheimer’s disease two‐center study resulted in regulatory clearance in the European Community in 2018. Shockwave stimulation of the brain is meanwhile called TPS (Transcranial Pulse Stimulation). Typical treatment consists of 6 sessions within 2 weeks, each session with 6000 pulses at 0.2mJ/mm2.ResultThere is worldwide an increasing number of clinical sites (over 75) with successfully treated Alzheimer’s patients. There have been meanwhile over 5000 sessions performed. No side effects have been reported. The feedback from patients, their relatives and physicians is overwhelmingly positive. Examples of testimonials will be presented. Additionally, placebo controlled trial is ongoing.ConclusionTPS treatment of the mild and moderate Alzheimer’s disease with shockwaves results in significant reduction (10‐15%) of the disease symptoms. Treatment protocols for maintaining this improvement over longer period of time are under evaluation. The treatment is effective and safe.
Pre vs post‐task modulation of resting state EEG functional connectivity and network topology
Authors: Požar Rok , Giordani Bruno , Kavcic Voyko 
Published: December 2022

AbstractBackgroundRecently, we have shown a significant decrease in resting‐state EEG (rsEEG) spectral power at post‐task as compared to pre‐task cognitive engagement in older adults. Further, older adults with mild cognitive impairment (MCI) showed greater decreases in rsEEG in temporal and central cortical regions at post‐task than healthy controls (HC). Here, we present functional connectivity (FC) and network topology derived from the same pre‐ to post‐rsEEG changes.MethodWe studied a sample of community dwelling African American older participants over age 60 years, consisting of consensus‐based diagnosis for 58 HC and 41 MCI. rsEEGs were recorded before and after approximately 20 minutes of a visual motion direction discrimination task. FC between channels was assessed by the phase lag index, while minimum spanning tree (MST) was used to characterize network topology.ResultFor both HC and MCI groups, when compared to pre‐task measurements, the post‐task FC was significantly increased within the middle frontal, middle central, and left temporal regions in the lower alpha frequency band. An opposite pattern with decreased FC was found within the right parietal region in the delta, theta, lower alpha, upper alpha, and beta frequency bands. In contrast, compared to HC, the MCI group did show significantly decreased FC within the middle frontal region in the delta band, following the cognitive task. All results from network topology failed to demonstrate differences between HC and MCI. On average, both groups' post‐task functional network topology showed significant decreased eccentricity and diameter in the delta and beta bands, indicating a higher global network integration.ConclusionOur findings suggest that visual‐based cognitive engagement affects both post‐task FC and network topology similarly in both HC and MCI. For the most part, increased FC and functional topology in both groups are likely associated with after‐task effects, resulting from additional time to return to baseline, though decreased FC in MCI as compared to HC was seen within the middle frontal region in the delta. Our results demonstrate that both FC and topoloty are responsive to cognitive challenge, though frontal/executive‐driven differences in FC may be an area of future promise in distinguishing HC and MCI.
Neurovascular Uncoupling in TgF344‐AD Rats is Associated with Reduced Cerebral Capillary Endothelial Kir2.1 Expression
Authors: Fang Xing , Border Jane J. , Crumpler Reece F. , Strong Luke B. , Roman Richard J. , Fan Fan 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) is an emerging global health care crisis. Although reduced cerebral blood flow (CBF) is an early and persistent symptom in developing cognitive deficits, the underlying molecular and cellular mechanisms remain unclear. Recent studies suggested that restoration of capillary endothelial cells (ECs) inward‐rectifier potassium channels (Kir2.1) currents reversed cerebral hypoperfusion and enhanced neurovascular coupling in AD mice. The present study aims to investigate whether capillary ECs Kir2.1 expression is reduced in TgF344‐AD rats and whether it contributes to neurovascular uncoupling and cognitive deficits.MethodThree to six months old TgF‐344 AD rats expressing mutant human APP and PS1 and their age‐matched wildtype (WT) rats were studied. An eight‐arm water maze was used to test spatial learning and short and long‐term memory. Brain perfusion was mapped with a laser speckle imaging system. Whisker stimulation‐induced functional hyperemia was measured using laser Doppler flowmetry in vivo. Brain Kir2.1 expression was compared using western blot. Cerebral parenchymal arterioles (PAs) with attached capillaries were freshly isolated from AD and WT rats and mounted in a pressure myography. PAs response to capillaries focally injected KCL (10 mM) and Kir2.1 inhibitor (ML133) was compared.ResultAD rats exhibited learning and memory dysfunction at 6‐month of age compared with WT controls. However, cerebral hypoperfusion was observed in AD rats starting from 4‐month of age. Similarly, impaired functional hyperemia in AD rats started at 4‐month of age, which was exacerbated in 6‐month old AD rats. The expression of Kir2.1 in 6‐month AD brain tissue was significantly lower than in WT rats. AD PAs displayed less vasodilation (110.96 ± 3.92 % vs. 122.93 ± 1.97 %) and vasoconstriction (92.16 ± 3.47 % vs. 78.04 ± 2.96 %) in response to capillary administered KCL and ML133, respectively, compared to WT vessels.ConclusionReduced brain hypoperfusion precedes cognitive impairment in AD rats, associated with attenuated capillary EC Kir2.1 expression and neurovascular uncoupling.
Preclinical Detection and Monitoring of Alzheimer’s Disease Using a Multi‐Disease Diagnostic Platform Employing Autoantibodies as Blood‐based Biomarkers
Authors: DeMarshall Cassandra , Viviano Jeffrey , Emrani Sheina , Godsey George , Sarkar Abhirup , Belinka Benjamin , Libon David , Nagele Robert ,   Parkinson's Study Group, Alzheimer's Disease Neuroimaging Initiative
Published: December 2022

AbstractBackgroundEvidence for the universal presence of serum autoantibodies and their potential diagnostic utility for detection of Alzheimer’s disease (AD) and other neurodegenerative diseases has been extensively demonstrated by our laboratory. It is well known that AD‐related pathological changes in the brain can begin up to a decade before patients experience telltale symptoms, yet preclinical detection remains an unmet goal. In the present study, we demonstrate the utility of a panel of AD‐related autoantibodies capable of detecting AD at the earliest points along the AD continuum, including preclinical AD, years before the onset of symptoms, and prodromal AD (mild cognitive impairment, MCI).MethodUsing a customized panel of AD‐specific autoantibody biomarkers and Luminex xMAP® technology, sera from ADNI subjects with preclinical AD or MCI were screened to demonstrate both preclinical and prodromal AD detection. A panel of eight autoantibodies with increased titer in MCI and preclinical AD relative to controls was evaluated using both Random Forest and Receiver Characteristic Operating curves for their ability to distinguish diseased subjects from age‐ and sex‐matched controls, as well as from individuals with other neurodegenerative and non‐neurodegenerative diseases.ResultResults showed that the panel of eight autoantibody biomarkers was capable of differentiating patients with MCI from corresponding age‐ and sex‐matched controls with high overall accuracy, sensitivity, and specificity. These biomarkers were also capable of identifying cognitively normal subjects who later converted to MCI and AD, years before the clinical onset of their symptoms. This autoantibody biomarker panel readily distinguished MCI and preclinical AD subjects from Parkinson’s disease and breast cancer subjects, demonstrating excellent disease specificity.ConclusionResults demonstrate the utility of our custom Luminex xMAP® blood‐based autoantibody biomarker panel as an accurate, non‐invasive, and inexpensive diagnostic screener, not only for the detection of prodromal AD, but also the earlier stages of pathology, several years before the first onset of telltale clinical symptoms. This appears to be a multi‐disease diagnostic and disease‐staging strategy, since it has been demonstrated to be useful for a multitude of neurodegenerative diseases including both early‐stage AD and PD, as well as Multiple Sclerosis, with other disease applications currently underway
Scientific challenges underlying adaptation of existing cognitive tests or development of new tests to address cultural and linguistic diversity
Authors: Bowden Stephen C 
Published: December 2022

AbstractBackgroundHigh quality cognitive assessments may be a requisite part of care for people with any disease associated with cognitive changes. While extensive research has been devoted to development of reliable and valid cognitive assessment in some cultures, the development of cognitive assessments that address cultural and linguistic diversity has been relatively neglected.MethodThis talk will provide a conceptual overview of the principal scientific issues involved in developing culturally‐sensitive and scientifically robust assessments of cognition. The issues will be illustrated with examples of successful application of these principles, together with limitations. Recent research highlighting the risks of over‐interpretation of normative comparisons across cultural or ethnic diversity will be highlighted.ResultTwo broad scientific precepts underpin development of any new cognitive test. The first of these involves establishing construct validity, that is, the scientifically defensible measurement of target cognitive functions. Secondly, a normative basis for individual assessment is desirable.Regarding the first of these requirements, establishing construct validity can most efficiently triangulate from established cognitive measures, for example, informed by the best available model of cognitive abilities, namely the Cattell‐Horn‐Carroll model. Using the empirical methods of convergent and discriminant, any new test can be evaluated for convergence on construct estimation, within the limits of measurement error, with an established test of the target construct developed in another culture. The best available methods for this purpose involve multi‐group confirmatory factor analysis, which allows evaluation of measurement invariance (MI). If established, MI permits generalization of construct validity research across cultures.Regarding the second broad requirement, representative normative samples are ideal for individual assessment, but are expensive. An alternative is to use an individual baseline approach where repeat assessment within any one patient provides the control standard against which to monitor change, for example, in response to progressive disease. Methods for evaluating the reliability or precision of repeat assessments will be briefly delineated.ConclusionProviding rigorous cross‐cultural assessment of dementia and other cognitive disorders entails addressing significant scientific challenges. However, all of challenges fall within established methods that are readily available to researchers.
Development and Validation of a Cognitive Evaluation tool for Multilingual Populations: The Visual Cognitive Assessment Test (VCAT)
Authors: Kandiah Nagaendran , Soo See Ann , Lim Levinia , Leow Yi Jin , Vipin Ashwati , Ng Kok Pin 
Published: December 2022

AbstractBackgroundWith increasing research into novel disease modifying therapies for mild cognitive impairment (MCI) and mild dementia, there is a need for large scale early detection of cognitive disorders. However, existing cognitive evaluation tools largely cater for native English speakers. We designed and validated a novel visual based cognitive evaluation tool that could be applied to multilingual populations worldwide without the need for translation.MethodsThe development of the VCAT included pilot testing of individual test items, test refinement and development of a field version of VCAT. The test items covered domains of episodic memory, executive function, visuospatial function, semantic language and attention. The initial validation was carried out in a single centre cohort from Singapore comprising of cognitively normal (CN), MCI and dementia participants. Subsequent validation was carried out in centres across four Southeast Asian countries including Singapore, Malaysia, Indonesia and Philippines. Additional evaluation of construct validity against comprehensive neuropsychological test battery has been performed. Further validation in Canada, Brazil, India and South Korea is on‐going.ResultsIn the initial single centre validation in a cohort of 206 participants with a mean age of 67.8 (8.86) years and mean years of education of 10.5(6.0), the area under the curve (AUC) of VCAT for detection of cognitive impairment, CI (MCI and mild dementia) was 93.3 (95% CI 90.1 to 96.4). The Se and Sp of VCAT for the diagnosis of CI were 85.6% and 81.1%, respectively. In a wider Southeast Asian multicentre cohort of 284 participants, VCAT had an AUC of 90.5 (95% CI 87.0‐94.0) in discriminating CN from CI. The multiple languages used to administer VCAT in the four countries did not significantly influence test scores. VCAT and its subdomains demonstrated good construct validity in terms of both convergent and divergent validity and good internal consistency (α = .74). Mean time‐to‐complete VCAT was 15.7 ± 7.3 min.ConclusionsThe VCAT without the need for translation in multilingual populations has demonstrated high accuracy for the detection of MCI and mild dementia.
Development of the Figure Memory Test and the Word Accentuation Test for the assessment of cognition in Brazil
Authors: Yassuda Monica Sanches , Gil Gislaine , Apolinario Daniel , Brucki Sonia Maria Dozzi , Caramelli Paulo , Nitrini Ricardo 
Published: December 2022

AbstractBackgroundIn low‐ and middle‐income countries, the educational level of the population tends to vary significantly and persons with no literacy are in high numbers. In addition, countries with vast territories, such as Brazil, present significant differences in culture and language. These facts pose challenges for cognitive assessment. To this date, most cognitive tools used in Brazil have been developed in high‐income nations, and later, culturally and linguistically adapted for use in the country. Yet, some instruments, such as the Figure Memory Test (FMT) of the Brief Cognitive Screening Battery and the Brazilian Word Accentuation Test (WAT‐Br) have been developed in Brazil.MethodFMT: The FMT was developed to assess episodic memory among individuals with low or no education. Twenty black‐and‐white figures were selected to compose the test because they were easily recognized and named in pilot testing with individuals with low education. Ten figures were selected as target and are named and encoded, and ten others were included as distractors in the recognition phase. In an initial study, 51 cognitively unimpaired individuals, 23 having no education, completed the FMT and other cognitive tests. WAT‐Br: The WAT‐Br was developed to assess pre‐morbid intelligence. An initial pool of 60 items was constructed and a final version of 40 items was derived by item response theory. A sample of 206 older adults underwent the WAT‐Br and a standardized neuropsychological battery. Independent ratings were performed by two observers in 58 random participants.ResultFMT: The FMT delayed recall scores did not differ between participants with (7.26 ± 1.56) and without education (6.87 ±1.52) (p = 0.458). No differences in FMT scores were observed when the literate group was divided according to mean years of schooling. WAT‐Br: The items showed moderate to high discrimination (α between 0.93 and 25.04) and spanned a wide range of difficulty (β between ‐2.07 and 1.40). The WAT‐Br was shown to have an excellent internal consistency (Kuder‐Richardson Formula 20 = 0.95) and inter‐rater reliability (intraclass correlation coefficient = 0.92).ConclusionThe FMT and the WAT‐Br proved to be valuable tools for estimating cognitive performance in Brazil.
Lower myelin content is associated with poorer gait variability in older adults with cerebral small vessel disease and mild cognitive impairment
Authors: Silva N‡rlon C‡ssio Boa Sorte , Liu‐Ambrose Teresa , Dao Elizabeth , Hsu Chun Liang , Tam Roger , Stein Ryan G , Alkeridy Walid Ahmed , Laule Cornelia , Vavasour Irene M 
Published: December 2022

AbstractBackgroundMobility decline is often observed in individuals with cerebral small vessel disease (cSVD). Loss of myelin in the cerebral white matter is a common feature of cSVD and could be one of the mechanisms contributing to poor mobility; however, this hypothesis remains to be tested. Using myelin water fraction (MWF), we investigated whether myelin content is associated with gait parameters in older adults with cSVD.MethodCross‐sectional data from individuals with cSVD and mild cognitive impairment were analyzed. Myelin content was assessed via MRI multi‐echo gradient and spin echo T2 relaxation sequence, indexed as myelin water fraction (MWF). Gait parameters were measured using an electronic walkway. Hierarchical regression models adjusting for total intracranial volume, age, sex, body mass index, and Mini‐Mental State Examination were conducted to determine the associations between MWF and gait parameters. Significant models were further adjusted for white matter hyperintensity burden.ResultSixty‐four participants were included (mean [SD], age = 75.2y [5.4], 62.5% female). In adjusted models, lower MWF in the cingulum (Unstandardized B (95% CI): ‐5.12 [‐9.21 to ‐1.04], R2change = 0.09, Fchange = 6.31, pchange = 0.015), superior longitudinal fasciculus (‐3.79 [‐7.29 to ‐0.29], R2change = 0.07, Fchange = 4.70, pchange = 0.034), posterior corona radiata (‐4.86 [‐9.45 to ‐0.27], R2change = 0.07, Fchange = 4.49, pchange = 0.039), and body of the corpus callosum (‐4.19 [‐8.19 to ‐0.20], R2change = 0.06, Fchange = 4.41, pchange = 0.040) was associated with higher cycle time variability. White matter hyperintensity burden weakened these associations.ConclusionIn older adults with cSVD, Lower myelin content in specific white matter tracts may contribute to higher gait variability, increasing the overall risk of mobility impairment.
18F‐MK‐6240 Tau PET as a Biomarker for Chronic Traumatic Encephalopathy: Case Series of 10 Symptomatic Former National Football League Players
Authors: Alosco Michael L , Iaccarino Leonardo , Asken Breton M. , Nowinski Christopher , Mundada Nidhi S. , Smith Karen , Culhane Julia E , Shankar Ranjani , Windon Charles , Tripodis Yorghos , Mercier Gustavo , Stein Thor D. , Grinberg Lea Tenenholz , McKee Ann C. , Stern Robert A , Kowall Neil W , Miller Bruce L. , Mez Jesse B. , Killiany Ronald J , Rabinovici Gil D. 
Published: December 2022

AbstractBackgroundThe pathognomonic lesion of chronic traumatic encephalopathy (CTE) is the perivascular deposition of neuronal phosphorylated tau (p‐tau). Patchy p‐tau deposits initially accumulate in frontotemporal cortices. Medial temporal lobes (MTL) become involved in late stage. Validated in vivo biomarkers for CTE p‐tau do not exist. 18F‐MK‐6240 is a second‐generation tau PET ligand with improved imaging properties compared with first‐generation ligands, but its utility in CTE is unknown. We report initial results from an ongoing proof‐of‐concept study investigating MK‐6240 in people at risk for CTE.MethodTen older adult male symptomatic former National Football League (NFL) players completed tau (MK‐6240) and amyloid (florbetapir) PET imaging and neuropsychological testing. MK‐6240 data were acquired from 36 cognitively unimpaired males without traumatic brain injury history (but unknown contact sport history) from the Wisconsin Registry for Alzheimer’s Prevention (mean age=66.3, SD=6.3; mean MMSE=29.6, SD=0.5). Using cerebellar gray matter reference, 70‐90 min MK‐6240 SUVR images were created. W‐score (age‐adjusted z‐scores) maps were generated using the control data and thresholded at w>1.65 to visualize high binding voxels. Images and scatter plots of uptake in NFL players and controls were qualitatively assessed due to the small sample size.ResultsSample characteristics are in Table 1 (age range:51‐72, 5/10 Black). All NFL players had a negative florbetapir PET. 9/10 were cognitively impaired, particularly in memory and executive functions (Table 2). One former NFL player (case 4) had MTL MK‐6240 uptake greater than all controls, along with focal low intensity uptake in the superior frontal cortex (Figure 1). Two NFL players (cases 6 and 9) had mildly elevated MTL MK‐6240 uptake, particularly in entorhinal cortex and parahippocampus, though similar binding was seen in some controls (Figure 2). There was minimal MTL uptake in the remaining NFL players. Cortical uptake was complicated by contamination from off‐target meningeal binding.ConclusionsExisting data suggests current radioligands (e.g., flortaucipir) developed for Alzheimer’s disease might have restricted utility to late stage CTE. This might be true for MK‐6240 and off‐target meningeal binding complicates detection of cortical p‐tau. Data collection is ongoing and the larger data set will inform on MK‐6240 as a biomarker for CTE.