bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal viability/astrocyte activity ratio in the dorsolateral prefrontal cortex as a biomarker of Alzheimer’s dementia: A proton magnetic resonance spectroscopy study
Authors: Jha Shreya , Torres‐Carmona Edgardo , Iwata Yusuke , Ma Clement , Graff‐Guerrero Ariel , Fischer Corinne E. , Mulsant Benoit H. , Pollock Bruce G. , Rajji Tarek K. , Kumar Sanjeev 
Published: January 2025

AbstractBackgroundN‐acetyl‐aspartate (NAA) and myo‐inositol (mI) are neurometabolites reflecting neuronal viability and astrocyte activity, respectively. These can be quantified in vivo using proton magnetic resonance spectroscopy (1H‐MRS). Previous studies have suggested that these metabolites could serve as biomarkers for Alzheimer’s disease dementia (AD). NAA and mI levels were compared in the dorsolateral prefrontal cortex (DLPFC) between AD and cognitively healthy control participants to assess for significant differences, assess if NAA/mI ratio can distinguish the two groups, and to explore the relationship between metabolites and cognition.MethodParticipants with AD and HCs over 55 years old were included. Bilateral NAA and mI levels were quantified in the DLPFC using 3T proton magnetic resonance spectroscopy (point‐resolved spectroscopy, echo time=35ms). NAA and mI levels were estimated using LCmodel version 6.3 and reported in H2O ratios i.e. NAA/ H2O or mI/H2O.ResultThe study included 64 participants, 41 with AD (mean (SD) age = 75.2 (7.2) years, females = 58.5%), and 23 HC (age = 72.2 (7.7) years, females = 60.1%). Bilateral NAA levels in the DLPFC were lower in AD vs. HC, (t(62)=‐2.5, p =0.02); however, mI levels in the DLPFC did not differ between the two groups t(62)=1.0, p=0.35. NAA/mI ratio was lower in AD vs. healthy (t(62)= ‐2.368, p =0.02). The NAA/mI ratio at a cut off value of 1.69 showed 59% sensitivity and 87% specificity at distinguishing AD from HC. NAA levels were associated positively with global cognition.ConclusionDLPFC NAA is decreased in AD and is associated with cognition. NAA/mI ratio shows good specificity in distinguishing AD from the control group, suggesting its role in complementing other biomarkers in ascertaining AD. Future studies should prospectively evaluate the clinical utility of NAA/mI ratio as a biomarker in AD.
Evaluating the use of eye tracking tasks as language‐ and culturally‐neutral assessments of cognition in a multi‐ethnic cohort of older adults
Authors: Yep Rachel , Nyman Alexander J , Gopinath Georgia , Alexander Madeline Wood , Marawi Tulip , Boshmaf Silina Z , Brien Donald C , Coe Brian C , Pople Christopher B , Munoz Douglas P , Ryan Jennifer D , Black Sandra E , Goubran Maged , Rabin Jennifer S 
Published: January 2025

AbstractBackgroundCanada and the United States are both aging and becoming increasingly diverse. Despite this demographic shift, non‐White racial/ethnic groups remain underrepresented in research on cognitive impairment and dementia. A major barrier to inclusivity is the lack of cognitive assessments that are valid in individuals with diverse language and cultural backgrounds. Eye tracking tasks can potentially overcome this barrier since they do not require verbal responses and use culturally neutral stimuli. Here, we tested this hypothesis by comparing performance on standard neuropsychological tests and eye tracking tasks across individuals from White and underrepresented ethnic groups (UEG).MethodParticipants were cognitively unimpaired adults enrolled in the Canadian Multi‐Ethnic Research on Aging (CAMERA) study. Participants completed a battery of standard neuropsychological tests and two well‐characterized eye tracking tasks: the interleaved pro/anti‐saccade task (IPAST), which assesses executive function, and the visual paired comparison task (VPCT), which assesses visual memory.ResultWe included 54 participants (mean age=68.68±6.91, 70% female) with a Clinical Dementia Rating global score of 0. Among them, 22% of participants self‐identified as White (n=12) and the remaining participants identified as being from an UEG (n=42; 37% East Asian, 37% South Asian, 4% Other). Linear regression models assessed whether ethnic background (White vs. UEG) was associated with task performance after adjusting for age, sex, and years of education. We found that ethnic background influenced performance on several standard neuropsychological tests, including the MoCA (β=0.26, p=0.03), phonemic fluency (β=0.29, p=0.02), category fluency (β=0.38, p=0.003), and Benson Complex Figure delay (β=0.23, p=0.08), such that the UEG group had lower scores. There were no group differences on Trails A and B or the Symbol Digit Modalities Test (p‐values>0.1). Importantly, ethnic background did not influence performance on either eye tracking task (IPAST: β=‐0.17, p=0.17; VPCT: β=0.02, p=0.83).ConclusionOur preliminary results suggest that ethnic background influences performance on several standard neuropsychological tests, but not performance on the IPAST or VPCT. With further validation in larger samples, these eye tracking tasks may provide a brief and language‐free way to screen and monitor cognitive impairment in diverse samples currently underrepresented in dementia research.
Distinct CSF proteomic signatures are associated with cognitive decline in A+T+ and A+T‐ individuals with MCI due to Alzheimer’s Disease
Authors: Vromen Eleonora M. , van Harten Argonde C. , Teunissen Charlotte , van der Flier Wiesje M. , Pijnenburg Yolande A.L. , Visser Pieter Jelle , Tijms Betty M. 
Published: January 2025

AbstractBackgroundIndividuals with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) show variability in cognitive decline. Little is known about the underlying mechanisms, but these are likely to depend on tau levels. Using untargeted proteomics in cerebrospinal fluid (CSF), we studied which processes were associated with cognitive decline in A+T‐ and A+T+ MCI individuals.MethodWe included 80 individuals from ADC (age 66±7.9 years, 28 (35%) women, 52 (66%) A+T+, 4.6±2 follow‐ups over 4.1±1.8 years). N=2323 CSF proteins were quantified at baseline using untargeted TMT LC‐MS/MS. We tested associations between each protein and 1) progression to dementia with Cox proportional hazard models and 2) decline over time on MMSE using linear mixed models with subject‐specific intercepts. All analyses were stratified for tau status and adjusted for age, sex and education. We performed enrichment analysis on proteins associated with cognitive decline.ResultBoth AT groups declined over time on MMSE, with steeper decline in A+T+ (A+T+ β±SE ‐0.99±0.08 p‐value<0.001, A+T‐ β±SE ‐0.39±0.09 p‐value<0.001, p‐valueA+T‐ vs. A+T+<0.001). Largely different groups of proteins predicted faster progression to dementia and steeper decline on MMSE in A+T+ (resp. n=119 and n=664, p‐values<0.05, Figure 1) compared with A+T‐ individuals (resp. n=88 and n=718, p‐values<0.05). In A+T+ higher levels of proteins associated with synaptic plasticity processes and extracellular matrix organization, and lower levels of proteins associated with immune system processes and lipid remodeling were associated with steeper cognitive decline. Conversely, in A+T‐ these processes were associated with slower cognitive decline. Furthermore, in A+T‐ proteins indicative of blood‐brain barrier (BBB) impairment were also associated with cognitive decline.ConclusionA+T+ and A+T‐ individuals with MCI show largely different proteomic signatures associated with cognitive decline. In A+T+ MCI individuals, higher levels of synaptic‐plasticity proteins and lower levels of immune‐related proteins were associated with faster cognitive decline, while in A+T‐ opposite effects were found. This suggest that treatments to slow cognitive decline in AD may need tailoring on tau status.
Amyloid‐PET disclosure in Subjective Cognitive Decline: patient experiences and outcomes over time
Authors: Hendriksen Heleen M.A. , de Rijke Tanja J. , Smets Ellen M.A. , Fruijtier Agnetha D. , van de Giessen Elsmarieke , van Harten Argonde C. , van Leeuwenstijn Mardou S. S. A. , van der Schaar Jetske , Trieu Calvin , Visser Denise , Visser Leonie N.C. , van der Flier Wiesje M. 
Published: January 2025

AbstractBackgroundCommunicating amyloid‐status and the subsequent risk of future cognitive decline to individuals with Subjective Cognitive Decline (SCD) is complex. Insight into how individuals with SCD evaluate the disclosure process and its impact could help optimize current practice. Therefore, the aim of our study was to examine experiences with, and outcomes of, amyloid‐PET disclosure in individuals with SCD over time.MethodFifty‐seven participants from the Subjective Cognitive Impairment Cohort (SCIENCe) (66±8yrs, 21(37%)F, MMSE 29±1, 15(26%) amyloid positive (A+)) completed questionnaires one week prior (T0), one day after (T1) and six months after amyloid‐PET disclosure (T2). Questionnaires addressed patient‐reported experiences (satisfaction with the consultation, evaluation of the provided information, and decision regret) and outcomes (emotions and behavioral (intentions to) change). We analyzed open‐ended questions thematically and tested effects of amyloid‐status and/or time using Repeated Measures ANOVA, χ², Mann‐Whitney U, and Independent Samples t‐tests.ResultIndependent of amyloid‐status, participants were satisfied with the consultation (scale 1‐10; 7.9±1.7) and the provided information (scale 1‐4; T1:3.3±0.9, T2:3.2±0.8). After six months, A+ participants reported significantly more information needs (45% vs. 12%, p=.02), e.g. about drug research and advice on what can be done to slow down disease progression. Decision regret was low, independent of amyloid‐status (scale 1‐5; A+:1.5±0.9, A‐:1.4±0.6, p=.525). Participants mentioned to appreciate information about their own health status and the possibility to act on this information. After six months, A+ participants more often reported to have recorded their wishes for the future (scale 1‐7; median(IQR): A+: 5(4‐7), A‐: 3(1‐4), p=.023). Negative emotions remained low overall over the six‐month period, independent of amyloid‐status (negative affect: F(2, 82) = 1.884, p=.158, pinteraction=.997; uncertainty: F(2, 86) = 1.258, p=.289, pinteraction=.618; anxiety: F(2, 80) = 1.014, p=.368; pinteraction=.728).ConclusionParticipants with SCD evaluated amyloid‐PET disclosure positively, regardless of amyloid‐status. Amyloid‐PET disclosure did not induce negative emotions and participants did not regret learning their result. The reported need for information after six months, especially among A+ individuals, underscores the importance of follow‐up.
Polygenic predisposition to white matter hyperintensities does not contribute to amyloid or tau progression in Alzheimer’s disease
Authors: Zheng Lukai , Frerich Simon , Franzmeier Nicolai , Malik Rainer , Ewers Michael ,   Alzheimer's Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundWhite matter hyperintensities (WMH) are prevalent Alzheimer’s disease (AD). However, the role of WMH in the etiology of AD is debated. Specifically, a key question is whether higher WMH is predictive of higher beta‐amyloid (Aβ) and fibrillar tau accumulation. Here, we assessed whether a genetic predisposition to higher WMH (assessed via polygenic score [PGS] of WMH based on a large‐scale population‐based GWAS) is associated with higher rates of WMH volume and amyloid‐ and tau‐PET accumulation in elderly individuals.MethodsWe included 338 participants within the AD spectrum defined by amyloid‐PET positivity, encompassing 135 cognitively normal (CN Aβ+), 122 mild cognitive impairment (MCI Aβ+), 81 AD dementia, and in addition 287 amyloid‐negative controls (CN Aβ‐) from from ADNI. Flortaucipir‐PET was available in a subset of 92 Aβ+ & 85 CN Aβ‐ participants. WMH were segmented via a deep learning‐based algorithm on FLAIR images and partitioned into 5 lobar volumes. Based on GWAS in 35,000 individuals from the UKBiobank with global WMH volume as the dependent variable, we generated a PGS including 20 SNPs (p<5×10−8). Centiloids of global cortical amyloid‐PET and temporal‐meta ROI values of tau‐PET SUVR were computed. All linear regression analyses were stratified by group (CN Aβ‐ vs pooled Aβ+) and controlled for age, sex, education, systolic blood pressure, BMI, APOE e4 genotype, and population genetic components.ResultsA higher PGS was associated with higher cross‐sectional WMH volume in the frontal, parietal, and temporal lobes in both the CN Aβ‐ and the whole Aβ+ group (except for temporal WMH; Figure 1). Longitudinally, higher PGS was associated with faster increases in frontal WMH volume in CN Aβ‐ (β=0.18, p=.03) and in the temporal lobe in the Aβ+ group (β=0.18, p=.01, Figure 2) over 2.8 years on average. Conversely, neither PGS nor baseline WMH volume (or modifiable risk factors) predicted increase in amyloid‐ or tau‐PET (mean follow‐ups: 3.9 & 2.8 years).ConclusionGenetic predisposition to WMH was associated with higher WMH volume in a region‐dependent manner, but the increases in WMH were associated neither with Aβ‐ nor tau‐PET accumulation, suggesting that white matter lesions develop independently from AD pathologies.
A pandemic preparedness plan for common neurodegenerative diseases: a JPND advice report
Authors: Splinter Marije J. , Henderson Emily J. , Ben‐Shlomo Yoav , Wolters Frank J. , Darweesh Sirwan K.L. , Sowa Pawel , Velek Premysl , de Schepper Evelien I.T. , Ikram M. Kamran , Licher Silvan 
Published: January 2025

AbstractBackgroundThe expected seasonal recurrence of (new variants of) COVID‐19 and the emergence of other airborne infectious diseases underscore the need for a sustainable healthcare preparedness strategy. It is particularly essential to ensure equitable access to healthcare for individuals with chronic diseases, including dementia and Parkinson’s Disease. Moreover, it is vital to provide clinicians and researchers in the neurodegenerative disease fields with resources and infrastructure to ensure continuity of their work, even during a pandemic.MethodsWe established an international collaboration and invited not only researchers and clinicians, but also patient representatives from the Netherlands, Poland, and the United Kingdom. We co‐created a pandemic preparedness plan building upon insights and experiences from a total of 25.000 participants from four population‐based studies during the COVID‐19 pandemic. Between March and November 2023, we organized two hybrid meetings in Bristol (United Kingdom) and Rotterdam (the Netherlands), and two online meetings. Key aspects of the plan included lessons learned in healthcare provision, healthcare utilization, and conducting research that could be applied during future pandemics.ResultsDuring the group meetings, we outlined three fundamental elements of remote data collection during health crises: validated questionnaires, variated response options, and questionnaire testing within and beyond the research group. Additionally, we addressed the potential burden of participating in these studies for frail individuals, providing specific considerations about questionnaire length, readability, and the added value of supporting participants in completing a questionnaire. Finally, we made recommendations about data sharing, underlining the importance of legislative measures extending beyond the COVID‐19 pandemic, which are crucial for enabling successful integration and long‐term utilization of multiple data sources. Beside research‐related recommendations, we also shared clinical perspectives, including the risks of social isolation for individuals with dementia and Parkinson’s Disease, the dynamics of remote versus in‐person consultations, and the concept of moral injury among healthcare professionals who provided care for infected individuals during the pandemic.ConclusionIn this pandemic preparedness plan, we provide research and clinical recommendations and insights specifically tailored to the neurodegenerative disease fields. This establishes an essential framework for setting up new studies and safeguarding research and clinical practices when a new pandemic emerges.
Sex‐ and lineage‐specific effects of cannabidiol in mouse models of Alzheimer’s Disease – a PET scan and behavioral study
Authors: Spelta Lidia Emmanuela Wiazowski , Righini Chiara Maria , Brizola Jean Marques , de Paula Faria Daniele de Paula 
Published: January 2025

AbstractBackgroundEmerging preclinical studies show that cannabidiol (CBD) has neuroprotective and anti‐inflammatory effects that may have the potential to improve Alzheimer's disease (AD) therapy. Although much progress has been made in understanding the pathology of AD, its multifactorial nature can't be mimicked in a single preclinical model. In order to improve preclinical results and search for AD better interventions, the aim of this study is to compare the effects of CBD in two AD animal models in a sex‐dependent manner.MethodMale and female Ts65Dn and 3xTg‐AD mice were used in this study (Ethical approval 1811/2022). At 7 months‐old animals received CBD (20mg/kg, ip) or vehicle (etanol:tween‐80:saline) for 30 days. At 8 months‐old, animal behavior was evaluated in the open field to access exploratory behavior and memory, through the novel object recognition test. Animals were also inject with [18F]FDG (5.5MBq, iv) and [11C]PK11195 (29.6–7.4MBq, iv) to evaluate neurodegeneration and neuroinflammation by positron emission tomography (PET).ResultExploratory behavior had significant influence of sex, animal lineage and treatment. CBD‐treated male and female 3xTg‐AD mice traveled less distance in the open field than the Ts65Dn ones (p=0.025 comparing females; p=0.004 comparing males), and had a smaller velocity (p=0.008 comparing females and p<0,0001 comparing males). Also, in male Ts65Dn mice, the velocity was higher in CBD‐treated than in vehicle‐treated group (p=0.023). Considering memory, there was an effect of sex and CBD in 3xTg‐AD mice, as the long‐term‐memory recognition index was higher in CBD‐treated females than in males (p=0.01). Regarding whole brain PET, [18F]FDG uptake was higher in 3xTg‐AD males compared to females, in vehicle‐treated (p=0.001) and CBD‐treated (p<0.0001) groups. Also, in male animals [18F]FDG uptake was higher in 3xTg‐AD than in Ts65Dn treated with vehicle or CBD (p=0.028 and p=0.008, respectively). Finally, in vehicle‐females [18F]FDG uptake was lower in 3xTg‐AD compared to Ts65Dn mice (p=0.048). Considering [11C]PK11195 uptake, the only significant difference was a higher uptake in 3xTg‐AD vehicle‐treated males compared to females (p=0.014).ConclusionOur study highlights the importance of studying sex in preclinical research, as well the development of different mouse models for AD research. This would strengthen the translational power of preclinical research.
Association of Long‐Term BMI Change with Alzheimer‐Signature Cerebral Glucose Metabolism in Non‐Demented Older Adults
Authors: Lee Seunghoon , Yi Dahyun , Byun Min Soo , Kong Nayeong , Jung Joon Hyung , Chang Yoon Young , Keum Musung , Ahn Hyejin , Lee Jun‐Young , Lee Yun‐Sang , Kim Yu Kyeong , Kang Koung Mi , Sohn Chul‐Ho , Lee Dong Young 
Published: January 2025

AbstractBackgroundGrowing evidence suggests that low body mass index (BMI) or BMI decline from midlife is related to the risk of Alzheimer’s disease (AD) and related cognitive decline in later life. However, limited information is yet available regarding the underlying brain change that could explain such relationship. This study aims to investigate whether BMI and BMI change after midlife are associated with cerebral metabolism in late life.MethodA total of 268 non‐demented (193 cognitive normal and 75 mild cognitive impairment) older adults from 55 to 90 years of age were enrolled from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). Current or late‐life BMI was calculated using the measured height and body weight. Midlife (40 ∼ 50 years of age) BMI was calculated using self‐recall based midlife body weight and height. Self‐recall past body weight in cognitively healthy older adults was well‐validated1. All participant received [18F] fludeoxyglucose (FDG)‐PET at baseline. General linear model analysis was performed to assess the association between BMI and BMI changers with AD‐signature cerebral glucose metabolism (AD‐CM).ResultMidlife BMI had significant negative association with AD‐CM (p = 0.007). even after adjusting for age, sex, clinical deterioration rating (CDR) sum of box score, and apolipoprotein E ε4 positivity. Three strata of BMI change from midlife to late‐life (i.e., decreasing pattern: ≤ ‐4%, stable pattern: ‐4% < BMI change < 4%, increasing pattern: ≥ 4%) showed significantly different AD‐CM (p = 0.045). Post hoc comparison revealed that decreasing BMI pattern had significantly lower AD‐CM than increasing BMI pattern, while no difference was found between the decreasing pattern and stable pattern. Sensitivity analyses for cognitively normal participants showed similar results.ConclusionThe findings suggest a close association between long‐term BMI decline from midlife and cerebral hypometabolism in late life. Such brain hypometabolism may serve as a potential neural substrate for BMI reduction‐related cognitive decline or increased risk of AD in older adults.References1. Kyulo NL et al. (2012) Validation of recall of body weight over a 26‐year period in cohort members of the Adventist Health Study 2. Ann Epidemiol 22, 744‐746.