bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma neurofilament light chain predicts Alzheimer’s disease in patients with subjective cognitive decline and mild cognitive impairment: a longitudinal study
Authors: Mazzeo Salvatore , Bagnoli Silvia , Ingannato Assunta , Padiglioni Sonia , Giacomucci Giulia , Manganelli Alberto , Cavaliere Arianna , Moschini Valentina , Balestrini Juri , Morinelli Carmen , Galdo Giulia , Emiliani Filippo , Polito Cristina , Piazzesi Diletta , Crucitti Chiara , Frigerio Daniele , Berti Valentina , Sorbi Sandro , Bessi Valentina 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD) and mild cognitive impairment (MCI) represent a target population for early detection of Alzheimer’s Disease (AD). Nevertheless, both MCI and SCD are common and heterogeneous conditions. We aim to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting AD and the progression of cognitive decline in patients with SCD and MCI.Method140 patients (45 SCD, 73 MCI, and 22 AD dementia [AD‐D]) underwent plasma NfL and CSF biomarker measurement at baseline. A subgroup of patients also underwent amyloid‐PET and 18F‐FDG‐PET brain scans. They were rated according to the A/T/N system and followed up for a mean time of 2.72±0.95 years. Forty‐eight (19 SCD, 29 MCI) had plasma NfL measurement also after two years from baseline.ResultNfL levels were higher in AD‐D than MCI and in MCI than SCD. In each group, patients with ATN profiles consistent with AD (A+/T+/N+ or A+/T+/N‐ [defined as ATN+]) had higher NfL levels (F[5,103] = 13.50, p<0.001, η2 = 0.396) than patients classified as ATN‐ (including patients with normal AD biomarkers, isolate Aβ pathology [A+] and non‐AD pathologic changes). NfL can distinguish ATN‐ and ATN+ patients with high accuracy (AUC = 0.82) and cut‐off values of 19.45 pg/mL in SCD and 20.45 pg/mL in MCI provide the highest Youden’s index. During the follow‐up, nine (30%) SCD patients progressed to MCI (p‐SCD) and 14 (29.79%) MCI patients developed AD‐D (p‐MCI). The previously defined cut‐off values identified p‐SCD with an 80.00% [95%C.I. = 65.69:94.31] accuracy. The rate of NfL change per year was higher in p‐MCI (3.52±4.06 pg/mL) as compared to np‐SCD (0.81±1.25 pg/mL) and np‐MCI (‐0.13±3.24 pg/mL) and np‐MCI (‐0.13±3.24 pg/mL) patients and in ATN+ (1.53±3.60 pg/mL) as compared to patients in the A+ group (‐0.97±1.66 pg/mL). A rate of change lower than 1.64 pg/mL can exclude progression to AD with a 92.86% (95%C.I. = 83.32:100) accuracy.ConclusionNfL concentration and change over time are increased in SCD and MCI patients with a biological demonstration of AD and can predict the progression of cognitive decline. Despite being considered a non‐specific neurodegeneration biomarker, if applied to selected populations, NfL may be a reliable, non‐invasive tool to detect the early stages of AD.
Navigational Decision‐Making Among Older Drivers: An Analysis of Real‐World Driving Patterns
Authors: Derafshi Reihaneh , Babulal Ganesh M. , Bayat Sayeh 
Published: December 2023

AbstractBackgroundDriving is an important aspect of independence for older adults. However, cognitive decline may impair driving abilities and safety. A deeper understanding of the impact of cognitive impairment on driving behaviours in older adults can inform public health strategies to support maintaining their ability to drive safely. This study investigates how older adults with and without cognitive impairment make navigational decisions (e.g., route choice) while driving in real‐world settings.MethodParticipants were enrolled in longitudinal driving studies at Washington University School of Medicine. GPS dataloggers tracked the daily driving patterns of 246 older drivers (aged 65+), including 230 cognitively normal older adults (CTL; Clinical Dementia Rating [CDR] = 0) and 16 older adults with cognitive impairment (DEM; CDR>0). Spatial clustering and hashing algorithms were employed to analyze each participant’s destinations and route choices. Trips with hard‐braking, sudden‐acceleration, and over‐speeding were considered “adverse behavior.” The Mann‐Whitney U‐test was performed to identify significant differences between the two groups.ResultThe CTL group had an average age of 68.2 ± 5.7 years and was composed of 46% females, while the DEM group had an average age of 69.2 ± 6.8 years and had 36% females. Additionally, the CTL group had a mean of 16.5 ± 2.3 years of education, while the DEM group had a mean of 16.0 ± 2.3 years of education. The results indicated that drivers with cognitive impairment had fewer full‐cycle trips (i.e., trips with the same start point and destination; p = 0.0165), visited fewer new destinations (p = 0.0210), used fewer distinct routes to reach their most common destination (p = 0.0174), and took fewer distinct routes to reach their most common destination when normalized by the average monthly frequency of this trip (p = 0.0062). No significant differences were observed in the other driving measures.ConclusionThis study reveals significant differences in driving patterns between cognitively normal older adults and those with cognitive impairment. Older adults with cognitive impairment exhibited more conservative driving behaviors, such as taking fewer full‐cycle trips and having less variety in their daily driving routes. These findings have important implications for designing interventions to improve mobility for older adults.
A neuropsychological investigation of social‐semantic knowledge in frontotemporal dementia
Authors: Rouse Matthew A , Halai Ajay D , Ramanan Siddharth , Patterson Karalyn , Rowe James B. , Ralph Matthew A Lambon 
Published: December 2023

AbstractBackgroundThe loss of semantic memory is a key feature of frontotemporal dementia (FTD), and is associated with atrophy of the anterior temporal lobes (ATLs). The role of the left and right ATLs in supporting social‐semantic knowledge is unclear. To address this, we developed a social‐semantic battery comprising exemplars of social concepts such as person‐specific knowledge, abstract social concepts, and understanding of social norms. Performance on this battery was directly compared with non‐social semantic knowledge, measured using the Cambridge Semantic Test Battery.Method48 people with FTD (behavioural‐variant FTD = 26, semantic dementia = 22), and 19 age‐matched healthy controls were recruited. Participants completed both semantic batteries, alongside tests of general cognition and executive function. Participants also underwent a 3T T1‐weighted structural MRI scan. All neuropsychological tasks were entered into a principal component analysis (with varimax rotation) to explore graded variations in cognitive performance in FTD. Voxel‐based morphometry was conducted to explore grey matter correlates of social and non‐social semantic knowledge. The relative contributions of the left and right ATL to social‐semantic knowledge were tested by including ATL volume and asymmetry indices as predictors in a multiple regression analysis.ResultPeople with SD and bvFTD were impaired in both social‐and non‐social knowledge tasks. The principal component analysis indicated separate components for semantic memory and executive function. Both social and non‐social semantic tasks loaded onto the semantic memory component (Figure 1). People with SD scored significantly worse than bvFTD on the semantic memory component (t = 5.18, p<0.0001), while people with bvFTD scored worse than SD on the executive function component (t = 3.97, p<0.001) (Figure 2). Semantic memory factor scores were correlated with grey matter in the bilateral ATLs (Figure 3). There were no significant clusters associated with scores on the executive function component. Multiple regression revealed that performance on the semantic memory component was predicted by the magnitude but not the asymmetry of ATL atrophy.ConclusionBoth social and non‐social forms of semantic knowledge are impaired by FTD, and this degradation is associated with bilateral ATL atrophy. These results suggest a shared representation for all types of semantic memory across the ATLs.
Contribution of clinical information to the predictive performance of plasma Aβ levels for Aβ PET positivity
Authors: Chun Min Young , Jang Hyemin , Kim Hee Jin , Kim Jun Pyo , Gallacher John , Allué Jose A , Sarasa Leticia , Castillo Sergio , Pascual‐Lucas María , Na Duk L , Seo Sang Won ,   DPUK
Published: December 2023

AbstractBackgroundEarly detection of β‐amyloid (Aβ) accumulation, a major biomarker for Alzheimer’s disease (AD), has become important. While Aβ deposition can be detected by positron emission tomography (PET), practical fluid Aβ biomarker is also being developed recently. In the present study, we aimed to determine whether APOE genotypes, age, and cognitive status increase the predictive performance of fluid Aβ levels for amyloid PET positivity.MethodsWe recruited 488 participants who underwent both plasma Aβ and Aβ PET studies (Cohort 1) and 217 participants who underwent both cerebrospinal fluid (CSF) Aβ and Aβ PET studies (Cohort 2). Plasma and CSF samples were analyzed using ABtest‐MS, an antibody‐free liquid chromatography‐differential mobility spectrometry‐triple quadrupole mass spectrometry method and INNOTEST enzyme‐linked immunosorbent assay kits, respectively. To evaluate the predictive performance of plasma Aβ and CSF Aβ, respectively, logistic regression and receiver operating characteristic analyses were performed.ResultsWhen predicting Aβ PET status, both plasma Aβ42/40 ratio and CSF Aβ42 showed high accuracy (plasma Aβ area under the curve (AUC) 0.814; CSF Aβ AUC 0.848). In the plasma Aβ models, the AUC values were higher than plasma Aβ alone model, when the models were combined with either cognitive stage (p < 0.001) or APOE genotype (p = 0.011). On the other hand, there was no difference between the CSF Aβ models, when these variables were added.ConclusionsPlasma Aβ might be a useful predictor of Aβ PET status as much as CSF Aβ, particularly when considered with clinical information.
Association of novel CSF biomarker candidates with cortical thickness in genetic frontotemporal dementia
Authors: Ullgren Abbe , Bergström Sofia , Rydell Melissa T. , Öijerstedt Linn , Remnestål Julia , Olofsson Jennie , Seelaar Harro , van Swieten John C. , Synofzik Matthis , Sanchez‐Valle Raquel , Moreno Fermin , Finger Elizabeth , Masellis Mario , Tartaglia Carmela , Vandenberghe Rik , Galimberti Daniela , Borroni Barbara , Butler Christopher , Ber Isabelle Le , Gerhard Alexander , Ducharme Simon , Laforce Robert , Rohrer Jonathan D. , Rodriguez‐Vieitez Elena , Månberg Anna , Nilsson Peter , Graff Caroline ,   the Genetic Frontotemporal Dementia Initiative (GENFI)
Published: December 2023

AbstractBackgroundA novel panel of 14 proteins measured in the CSF could separate individuals with genetic frontotemporal dementia (FTD) from controls, with most significant findings observed for neurofilament medium (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4) [1]. However, it is currently unknown whether these altered protein levels in the CSF reflect neurodegenerative changes in the brain. The aim of this study was to explore the cross‐sectional associations between the previously identified CSF biomarker candidates and cortical thickness in presymptomatic and symptomatic mutation carriers, and whether those associations differ by FTD mutation type.MethodWe have analyzed T1 MRI scans alongside concurrent CSF samples from 202 individuals from the GENFI cohort, belonging to families that carry FTD mutations in either C9orf72, GRN or MAPT genes. The study sample included symptomatic mutation carriers, presymptomatic mutation carriers and non‐carrier controls. Cortical thickness was estimated with FreeSurfer and CSF protein levels were measured via a multiplexed antibody‐based suspension bead array. The correlations between regional cortical thickness and protein levels were calculated via linear regression.ResultAltered levels of NEFM, AQP4, APOA1, PTPRN2, CTSS, SERPINA3, C4, AMPH and CD14 were all correlated with increased atrophy of at least one cortical region. Some effects were mutation specific, but NEFM, AQP4 and APOA1 correlated with atrophy in all mutation groups. We also observed mutation specific effects for 10 of the proteins. CTSS levels were only correlated with cortical atrophy in C9orf72 mutation carriers while NPTX2, VGF and PTPRN2 correlated with atrophy in GRN mutation carriers. In MAPT mutation carriers, 6 different proteins correlated with atrophy in the right temporal pole.ConclusionThe proposed fluid biomarker candidates continue to show promise and further longitudinal studies will contribute to elucidate their relationship to cortical atrophy and their prognostic value in genetic FTD.[1] Bergström et al. Mol Neurodegener. 2021; 16(1):79
Psychopharmacological Investigation to Explore the Neuroprotective Mechanism of Quercetin and Naringenin in an Experimental Model of Insulin Resistance and Related Cognitive Dysfunction
Authors: Kaur Sukhmanpreet 
Published: December 2023

AbstractBackground
Alzheimer’s disease is a brain ailment that causes cell degradation and is the leading cause of dementia, which is defined by a deterioration in thinking and independence in routine everyday activities. Insulin possesses neuroprotective and memory‐enhancing effects indicating a permissive function for insulin in cognition. Defective insulin signaling promotes Aβ aggregation and accelerates Aβ formation in the brain. Based on this evidence, Alzheimer’s is also defined as diabetes of the brain or Type 3 Diabetes.MethodDiabetes was induced in mice by Alloxan (100mg/kg) and sucrose 35% solution. Glucose level was monitored, and test drugs were given accordingly. Behavioral models employed in the current study were elevated plus maze, morris water maze, actophotometer, and novel object recognition test. Biochemicals performed were all mitochondrial complexes, glutathione level, protein carbonyl level, lipid peroxidase, and acetylcholinesterase activity. Histopathological evaluation of the hippocampal region was carried out under a bright field microscope.ResultAlloxan administration produced significant hyperglycemia characterized by a significant increase in serum glucose level as compared to the naïve. During the acquisition test (learning), alloxan‐treated mice significantly delayed the escape latency period to reach the submerged platform as compared to the naïve group. However, quercetin and naringenin administration significantly improved memory performance. In novel object recognition, alloxan treated spent more time near the familiar object, and the treatment group spent more time near the novel object. Alloxan treatment also disrupted the mitochondrial levels and lowered the antioxidant enzyme levels, whereas the treatment group significantly reversed the changes.ConclusionIn the present study, alloxan administration caused significant impairment in cognitive behavior as evidenced by the Morris water maze (MWM) test, increased fasting blood glucose oxidative stress [through alteration of endogenous antioxidant markers i.e. superoxide dismutase (SOD), and catalase antioxidant enzyme activity and reduced glutathione (GSH) levels and oxidative stress markers i.e. reactive oxygen species (ROS) and protein carbonyls levels] and increased acetylcholinesterase activity in different areas of the brain (frontal cortex and hippocampus). Administration of quercetin and naringenin in different doses significantly reversed alloxan administration‐induced behavioral, biochemical, and cellular alteration in both the frontal cortex as well as in hippocampus.
Managing Money: A Caregiver’s Guide to Finances: A Pragmatic and Scalable Evidence‐Based Program for Caregivers
Authors: Judge Katherine 
Published: December 2023

AbstractBackgroundFew programs have been developed that address the financial needs of caregivers. The following presentation discusses the development of an innovative 60‐minute interactive online program led by community educators.MethodContent includes a) Introduction to the Costs of Caregiving, b) Implications of Alzheimer’s disease, c) Benefits of Early Planning, d) Avoiding Financial Abuse and Fraud, e) Conversations about Finances, Assessing Financial and Legal Needs, and f) Finding Financial Support. A randomized controlled trial was used to examine efficacy with n = 164 participants assigned to the program condition and n = 158 participants assigned to the waitlist condition. Surveys were completed at a) Time 1 (baseline); b) Time 2 (after program completion); c) Time 3 (30 days after program completion); d) Time 4 (60 days after program completion); and e) Time 5 (90 days after program completion). Program participants also completed acceptability questions.ResultParticipants on average were 54 years old (SD = 15.34) with the majority female (80.4%), Caucasian (73.3%), and married (68.9%). Most participants worked part‐ or full‐time (54.9%), had a bachelor’s or post/professional degree (71.8%), and had yearly incomes of $50,000 or more (55.9%). Participants primarily provided care to a parent/in‐law (45%) or a spouse/partner (34.2%). Significant group differences between the program and the control conditions were found for the following outcomes: Perceived Knowledge (F(1, 174) = 4.54, p = .04); Financial Unmet Needs (F(1, 176) = 16.16, p = .01); Financial Unmet Needs Distress (F(1, 176) = 15.42, p = .01); Financial Self‐Efficacy (F(1, 174) = 6.19, p = .01); Financial Behavioral Intentions (F(1, 172) = 8.02, p = .01); and Financial Behavioral Actions (F(1, 172) = 13.05, p = .01). Post‐hoc analyses indicated short‐ and long‐term impacts that will be further discussed. In terms of acceptability, participants rated the program as highly acceptable, with 82.8% to 91.9% of participants rating each statement as ‘agree’ or ‘strongly agree’ and 91.9% of participants indicated they would ‘very likely’ recommend the program.ConclusionDiscussion highlights key features thought to contribute to the successful evidence‐based program including how to develop pragmatic and scalable programs and alignment of measures with program content and dose.
Evaluating Regional Importance for Tau Spatial Spread in Predicting Cognitive Impairment with Machine Learning
Authors: Doering Stephanie , McCullough Austin A. , Gordon Brian A. , Chen Charles D. , McKay Nicole S. , Hobbs Diana A. , Keefe Sarah J. , Flores Shaney , Hornbeck Russ C. , Xiong Chengjie , Hassenstab Jason J. , Bateman Randall J. , Ances Beau , Morris John C , Benzinger Tammie L.S. ,   the Dominantly Inherited Alzheimer Network (DIAN) Investigators
Published: December 2023

AbstractBackgroundCognitive decline in Alzheimer Disease (AD) is strongly correlated to the spatiotemporal pattern of tau‐protein neurofibrillary tangles (NFTs). Evidence suggests tau seeding spreads transneuronally in a prion‐like manner, a biological process distinct from NFT aggregation in previously‐affected regions. We previously proposed a method for quantifying global tau spatial spread (TSS) using tau positron emission tomography (PET) which found TSS is particularly informative in preclinical AD. The spread of tau pathology into specific regions may therefore be key to the onset of cognitive decline.Methods445 older adult and 21 younger control participants were recruited. Cognition was assessed with the Knight ADRC‐PACC and Tau‐PET images were parcellated using the Schaeffer400 atlas. For each region, TSS was calculated as the proportion of voxels with significant levels of tau. Abnormal voxels were identified by z‐scoring tau‐PET voxel‐wise relative to corresponding voxels in younger controls and then thresholded at z>1.96 for significance. This study predicted participant PACC from regional TSS using random forest regression (trained with 100 repeated 10‐folds). Feature importance (FI) was calculated with Mean Decrease in Impurity to identify regions in which tau spread is most significant to cognitive impairment.ResultsRegional TSS demonstrated highly saturated regions in the limbic and temporal lobes with progressively lower levels in peripheral regions, largely sparing the frontal lobe (Figure 1). However, the importance of regional spread in predicting cognition did not reflect the same spatial pattern (Figure 2). Four regions emerged with the highest FI in the limbic and default networks, indicating the spread of tau within these brain regions is key to predicting cognitive impairment (Table 1).ConclusionOur results suggest that tau pathology has spread extensively within medial and temporal regions early in AD. Regional TSS can be used to identify peripheral regions in which tau pathology is currently spreading into. As expected, limbic regions in the temporal lobe were critical to predicting participant cognitive impairment. However, regions in the temporal and parietal lobes belonging to the default network were additionally informative. Spread of tau pathology into new peripheral brain regions should therefore be evaluated when predicting future AD‐related cognitive decline.
The multidomain intervention trial for prevention of dementia among older adults with type 2 diabetes: a multi‐center, randomized, 18‐month controlled trial
Authors: Sugimoto Taiki , Araki Atsushi , Fujita Hiroki , Fujita Kosuke , Honda Keiko , Inagaki Nobuya , Ishida Takeshi , Kato Junichi , Kishi Minoru , Kishino Yoshinobu , Kobayashi Kazuki , Kouyama Kunichi , Kuroda Yujiro , Kuwahata So , Matsumoto Nanae , Noma Hisashi , Ogino Jun , Ogura Masahito , Ohishi Mitsuru , Shimada Hiroyuki , Sugimoto Kazuhiro , Takenaka Toshihiro , Tamura Yoshiaki , Tokuda Haruhiko , Uchida Kazuaki , Umegaki Hiroyuki , Sakurai Takashi ,   J‐MIND‐Diabetes study group
Published: December 2023

AbstractBackgroundThe aim of the Japan‐Multidomain Intervention Trial for Prevention of Dementia in Older Adults with Diabetes (J‐MIND‐Diabetes) was to examine the efficacy of multi‐domain intervention in prevention of cognitive decline in older adults with type 2 diabetes and mild cognitive impairment (MCI).MethodThe J‐MIND‐Diabetes is an 18‐month, multi‐centered, randomized controlled trial. Outpatients with type 2 diabetes aged 70‐85 years with MCI were recruited and randomized into multi‐domain intervention (management of metabolic and vascular risk factors, physical exercise, nutritional guidance, and promotion of social participation) and control groups (general instructions on dementia prevention) at a 1:1 allocation ratio using the stratified permuted‐block randomization methods. The primary outcome was a change from baseline to 18‐month follow‐up in a global composite score combining several neuropsychological tests, which include the MoCA‐J, the MMSE, the Rey‐Osterrieth Complex Figure Test (ROCFT), delayed recall test of a 10‐word list, the Digit Span, the Trail Making Test, the Digit Symbol Substitution Test, and the Letter Word Fluency Test.ResultBetween March 13, 2019, and May 8, 2020, 361 patients were screened and 154 were randomly assigned to the multi‐domain intervention group (n = 81) or control group (n = 73). 110 (71%) participants completed the trial. The full analysis set included 136 patients. In the primary efficacy analysis, there was no significant differences in the change of composite score from baseline to 18‐month follow‐up between the intervention group and the control group (mean difference 0.066 [95% CI ‐0.089 to 0.222]). In the analysis for each neuropsychological test, scores of immediate and delayed recall tests of the ROCFT in the intervention group significantly improved by a mean of 1.627 points and 1.793 points, respectively. The mean difference in the change of score of delayed recall test of the ROCFT between intervention group and control group was significant (mean difference 1.803 [95% CI 0.169 to 3.436]). In subgroup analyses, intervention effect on composite score was significant among patients with moderate to severe white matter hyperintensities (mean difference 0.351 [95% CI 0.088 to 0.614]).ConclusionThe multi‐domain intervention could improve memory function in older adults with type 2 diabetes and MCI.