bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of serum C‐reactive protein with in vivo cerebral beta‐amyloid deposition in nondemented older adults
Authors: Choi HyeJi , Byun Min Soo , Yi Dahyun , Jung Joon Hyung , Sohn Bo Kyung , Keum Musung , Jung Gijung , Ahn Hyejin , Lee Jun‐Young , Lee Yun‐Sang , Kim Yu Kyeong , Lee Dong Young ,   the KBASE Research Group
Published: January 2025

AbstractBackgroundC‐reactive protein (CRP) is widely used in clinical practice as a marker for inflammatory condition. Previous studies have examined the association between CRP levels in peripheral blood and Alzheimer’s disease (AD) dementia, but have yielded mixed results. In this study, we investigated the association between serum CRP levels and in vivo cerebral beta‐amyloid (Aβ) deposition in nondemented older adults.MethodNondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) cohort. All participants underwent 11C‐PiB‐PET/MRI and blood sampling. Serum CRP was measured by using a turbidimetric immunoassay (TIA) method. Since CRP level lower than 3 mg/L is considered as normal range in clinical settings, we classified the participants into two groups as follows: i) CRP < 3mg/L and ii) CRP ≥ 3mg/L. CRP values that deviated more than 3 standard deviations from the mean were considered outliers and excluded from analysis. Global cortical PiB uptake was used for measurement of global Aβ deposition. Both log‐transformed CRP and global PiB SUVR was used for analysis. Multiple linear regression analysis with CRP as an independent variable and global PiB SUVR as a dependent variable was performed adjusting covariates including age, sex, and apolipoprotein E ε4 (APOE4) positivity.ResultTotal 393 nondemented (260 cognitively normal and 133 mild cognitive impairment) older adults were included in the analysis. In CRP <3mg/L groups (N=393), CRP level showed significant negative association with global Aβ deposition, after adjusting age, sex and APOE4 positivity (β[SE] = ‐0.036 [0.015], p=0.018). In contrast, no significant association between peripheral blood CRP level and global Aβ deposition was observed when CRP level was higher than 3mg/L (N=37).ConclusionOur finding suggests that CRP in blood inversely relate to Aβ deposition in brain when the levels of CRP are within normal range (i.e., relatively low). However, such relationship appears not persist when CRP levels are higher than normal limit. Further studies are needed to understand the mechanisms underlying the relationship between peripheral CRP and cerebral Aβ accumulation.
Peak width of skeletonized mean diffusivity might be a better neuroimage marker for cognitive functions in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Authors: Lee Wei‐Ju , Huang Fan , Wang Shi‐Ming , Chen Hung‐Chieh , Chen Yi‐Ming , Huang Hsu‐Wen , Huang Chih‐Mao 
Published: January 2025

AbstractBackgroundCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a monogenic subcortical ischemic vascular dementia (SIVD) caused NOTCH3 gene mutations. Many different neuroimaging methods have been used to investigate the association between neuroimaging changes and clinical symptoms. We investigated the correlation between peak width of skeletonized mean diffusivity (PSMD) values and cognitive functions in preclinical CADASIL patients without a history of stroke or dementia, comparing them to white matter hyperintensities (WMH) volumes.MethodThis study recruited NOTCH3 R544C mutation carriers (n=63) without a history of stroke or dementia and age‐ and sex‐matched non‐carriers (n=35) in Taichung Veteran General Hospital. Brain MRI including T1, Fluid‐Attenuated Inversion Recovery (FLAIR), and diffusion tensor imaging (DTI) data were acquired on 1.5T MRI and neuropsychological assessments were used to evaluate the cognition functions for all participants. The domain‐specific composite Z‐scores were calculated to represent memory, executive function, processing speed, and visuospatial function. We examined the relationships between domain‐specific cognitive functions and both PSMD values and WMH volumes.ResultIn this study, the data from 65 participants carrying NOTCH3 R544C mutation and 35 non‐carriers were analyzed. Mutation carriers have more severe WMH (p < 0.001) and longer PSMD values (p = 0.011) compared to non‐carriers. After adjusting for age, sex, and years of education using partial correlation, the PSMD values are associated with processing speed (r = ‐0.252, p = 0.048) and visuospatial functions (r = ‐0.275, p = 0.03). The correlations between WMH volume and the cognitive functions were not statistically significant.ConclusionIn summary, the PSMD value might be a better imaging biomarker for the cognitive functions in preclinical CADASIL patients and represent the early subcortical cerebrovascular damage compared to WMH volumes.
Distinct dementia atrophy progression patterns associated with different epidemiological risk factors
Authors: Shapson‐Coe Alexander David , Waters Sheena , Oxtoby Neil P , Marshall Charles R 
Published: January 2025

AbstractBackgroundMost evidence about early structural brain change in dementia derives from highly selected disease cohorts. However, at population level, dementia is typically due to mixed pathologies. We aimed to characterise distinct patterns of brain volume change in early all‐cause dementia in a population cohort.MethodWe used the Subtype and Stage Inference (SuStaIn) algorithm to identify distinct subtypes of disease progression based on structural MRI in the UK Biobank cohort of 152 dementia cases, of which 31 were prevalent cases at the time of scanning and 121 were subsequent incident cases that had been scanned during the pre‐diagnosis phase. We compared other characteristics between subtypes to derive insights into potential aetiologies.ResultTwo distinct subtypes of progression were identified by SuStaIn, one that replicated the typical anatomy of Alzheimer’s disease (AD) with early atrophy of hippocampi and temporal cortex (n=82), and a less common subtype (n=34) characterised by early atrophy of the cerebellum, hippocampus and other subcortical structures, and likely to represent mixed AD and vascular pathologies. Individuals with the latter subtype had significantly higher levels of biomarkers associated with vascular disease, including body mass index (p=0.025) and burden of peri‐ventricular white matter hyperintensities (p=0.020). There was no difference in polygenic risk for Alzheimer’s disease or ApoE4 allele frequency between subtypes.ConclusionSubtype and Stage Inference provides a data‐driven approach to identifying distinct patterns of dementia progression. Within the UK Biobank cohort of dementia cases, these subtypes appear to be associated with distinct biological risk factors, which may improve our understanding of the earliest stages of dementia.
Characterizing brain structures associated with plasma neurofilament light chain among older adults: variations by sex and APOE gene
Authors: Dong Yi , Song Lin , Hou Tingting , Li Yuanjing , wang yongxiang , Du Yifeng , Qiu Chengxuan 
Published: January 2025

AbstractBackgroundPlasma neurofilament light (NfL) has emerged as a promising biomarker to track neurodegeneration in Alzheimer’s disease (AD) and other brain degenerative disorders. We sought to characterize brain structures and white matter lesions associated with plasma NfL among dementia‐free older adults, while taking into account demographic factors and genetic susceptibility (e.g., APOE gene).MethodThis population‐based cross‐sectional study included 844 non‐demented older adults (age ≥60 years, 59.2% women), derived from participants in the baseline assessments of the Multimodal INterventions to delay Dementia and disability in rural China (MIND‐China) study who had plasma NfL measured on the SIMOA platform in 2018 and undertook structural brain magnetic resonance imaging (MRI) scan on a 3T scanner in 2018‐2020. Structural brain measures were assessed using the Computational Anatomy Toolbox on the platform of MATLAB. Data were analysed using the multivariable linear regression models.ResultPer 1‐SD increase in log‐transformed NfL concentration was significantly associated with multivariable‐adjusted β‐coefficient (95% confidence interval) of 0.09 (0.05 to 0.14) for white matter hyperintensity (WMH) volume, 0.09 (0.05 to 0.14) for periventricular WMH volume, ‐2.71 (‐4.99 to ‐0.43) for grey matter volume, ‐0.03 (‐0.06 to ‐0.01) for entorhinal cortex volume, ‐0.04 (‐0.07 to ‐0.01) for parahippocampal volume, ‐0.22 (‐0.37 to ‐0.07) for AD‐signature volume, and ‐0.02 (‐0.03 to ‐0.01) for AD‐signature cortical thickness. The associations of plasma NfL concentration with the MRI markers of neurodegeneration were statistically evident mainly among males (P for plasma NfL×sex interaction<0.05) or APOE ε4 allele carriers (P for plasma NfL×APOE ε4 allele interaction<0.05).ConclusionBrain structures associated with increased plasma NfL in older adults are characterized by reduced grey matter volume, entorhinal cortex volume, parahippocampal volume, and AD‐signature volume, especially among men or carriers of the APOE ε4 allele.
Plasma p‐tau181 is associated with brain amyloid deposition and predicts MCI conversion to AD
Authors: Lin Yung‐Shuan 
Published: January 2025

AbstractBackgroundPlasma phosphorated tau 181 (p‐tau181) was found to change in concordance with amyloid PET and well before tau PET, suggesting that the secretion of p‐tau181 may represent a physiologic reaction to β‐amyloid plaques. Our study aimed to evaluate the relationship between amyloid PET plasma p‐tau181 and whether p‐tau181 predicts amnestic MCI to AD conversion.MethodWe included 98 participants (43 demented and 55 nondemented) who underwent florbetaben amyloid PET scan. Amyloid PET was interpreted by visual assessment based on brain amyloid plaque load score (BAPL). The plasma p‐tau181 level were tested using Simoa assays. Another longitudinal cohort of 37 amnestic MCI patients were tested plasma p‐tau181 level at baseline were followed up at for at least one year. ANOVA and logistic regression were used to evaluate p‐tau181 level between amyloid and cognitive status. Cox regression was used to examine p‐tau181 level and MCI conversion to AD.ResultBrain amyloid deposition was found in 51% (21/43) of the demented participants, and 11% (6/55) in the nondemented. The plasma p‐tau181 level was significantly higher in the amyloid positive individuals (p<0.001). P‐tau181 alone discriminates amyloid status with an AUC of (0.889, 95% CI 0.826–0.951). In the longitudinal amnestic MCI cohort, 49% (18/37) converted to AD during follow‐up. A P‐tau181 cutoff at 2.545 alone was able to predict conversion where higher Ptau181 has shorter conversion free survival (median survival time in month, 35.0 vs 14.0, p=0.029).ConclusionHigher plasma p‐tau181 was associated with brain amyloid deposition and MCI conversion to AD. Plasma p‐tau181 could be a surrogate blood‐based biomarker for amyloid positivity and predicts prognosis in MCI.
Building Care Partner Capacity Through Education on Behaviour Change in Dementia
Authors: Hickman Kathy 
Published: January 2025

AbstractCare Partners (family and friends) providing direct care to people living with dementia are 1.6 times more likely to report distress if the person they are supporting is experiencing behaviour changes according to the Canadian Institute for Health Information. These carers are a critical part of the care team and yet they are often not provided education needed to support high quality care and more effectively contribute to the care team.The Alzheimer Society of Ontario has developed a 6‐hour workshop (U‐First!® for Care Partners) for carers who are providing direct support to someone experiencing behaviour changes as a result of dementia or other cognitive impairment. This education is adapted from a similar program for direct health care providers and is intended to increase care partner confidence and skills to understand and respond to behaviour changes in order to i) reduce frequency and severity of behaviour changes; ii) enhance well‐being of care partners and people with dementia; iii) improve collaboration among all team members by creating common knowledge, language and approach to care. The program uses an interactive approach grounded in adult learning theory that has participants reflect on their experiences, engage with new content, practice using a variety of methods and plan how to implement what they have learned. Learners receive a participant workbook and an interactive application tool (U‐First!® Wheel), that helps them to think through potential causes of behaviour changes and supportive care strategies.Evaluation results show lasting impacts. Even at 6 months following completion of the program, participants reported increased ability and confidence to identify, flag and respond to behaviour changes, increased ability to identify risks, increased wellbeing for themselves (including reduced stress) and for the person they are supporting. In addition, they felt the program increased their ability to have positive interactions with the person they are supporting, other care partners and health care providers. Participants with perceived high levels of stress and/or low well‐being prior to the program experienced the greatest benefits in these areas and care partner perceptions of degree of concern about behaviour changes was positively impacted by participation in the program.
Alzheimer disease ATN imaging biomarkers across type 2 diabetes mellitus stages in diverse populations
Authors: Pillai Malavika , Ances Beau , O'Bryant Sid E. , Meeker Karin L. 
Published: January 2025

AbstractBackgroundType 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD) and disproportionately impacts under‐represented groups including Mexican Americans/Hispanics (MAs) and African Americans/Blacks (AAs) compared to non‐Hispanic Whites (NHWs). However, it remains unclear how amyloid, tau, and neurodegeneration (AT(N)) AD imaging biomarkers and cognitive functioning differ across diabetic stages including non‐diabetes, pre‐diabetes, and T2DM in a diverse community‐based cohort.MethodData were obtained from the well‐characterized Health and Aging Brain Study: Health Disparities (HABS‐HD) cohort, including MAs (n=612), AAs (n=676), and NHWs (n=725) with clinical, amyloid and tau positron emission tomography (PET), and cortical thickness measures from magnetic resonance imaging (MRI) scans. Diabetic stage was categorized by HbA1c values: non‐diabetes=HbA1c<5.7%; pre‐diabetes=HbA1c 5.7‐6.4%; and T2DM=HbA1c>6.4%. Differences in continuous measures of AT(N) imaging biomarkers and cognitive functioning (Mini‐Mental State Examination) across diabetes stage were determined using multivariate analyses of covariance (MANCOVAs). The interactive effect of diabetes stage and ethno‐racial group on AT(N) biomarkers and cognitive functioning was also assessed. Age, sex, white matter hyperintensity volume, and Clinical Dementia Rating (CDR) Sum of Boxes were included as covariates.ResultThe AD cortical thickness signature was significantly decreased in pre‐diabetes compared to non‐diabetes (p=0.001), and T2DM compared to non‐diabetes (p<0.001) and pre‐diabetes (p=0.04). Cognitive functioning was also decreased in pre‐diabetes compared to non‐diabetes (p=0.005), and T2DM compared to non‐diabetes (p<0.001) and pre‐diabetes (p=0.002). Amyloid and tau PET did not significantly differ across diabetes stages (p’s>0.05). Amyloid burden was significantly increased in NHWs compared to MAs and AAs (p’s<0.001). Cognitive functioning was significantly decreased in MAs compared to AAs and NHWs, and in AAs compared to NHWs (p’s<0.001). Tau PET and cortical signature did not significantly differ by group (p’s>0.05). MAs and AAs had higher incidences of pre‐diabetes/T2DM, but no interactions between diabetes stage and ethno‐racial group were observed for AT(N) biomarkers and cognitive functioning.ConclusionAD‐related neurodegeneration and cognitive functioning worsen in the earliest stages of diabetes. Although under‐represented groups have higher T2DM rates, the deleterious effects of higher HbA1c levels are ubiquitous across diverse populations. Treatment of T2DM may alleviate downstream AD decline and should be considered in AD clinical settings, studies, and trials.
Digitally Assessed Sleep Disturbances for Early Diagnosis of Alzheimer’s Disease
Authors: Krix Sophia , Odeh Joud , Lentzen Manuel , Val‐Guardiola Andrea , Martínez Neus Falgàs , Atreya Alankar , Conde Pauline , Doherty Aiden , Vairavan Srinivasan , Muurling Marijn , de Boer Casper , Curcic Jelena , Grammatikopoulou Margarita , Nikolopoulos Spiros , Brem Anna‐Katharine , Coello Neva , Narayan Vaibhav , Wittenberg Gayle , Duijn Cornelia M Van , Hinds Chris , Aarsland Dag , Sanchez‐Valle Raquel , Fröhlich Holger 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD.MethodWe modeled sleep patterns coming from the RADAR‐AD cohort from two sleep monitoring devices (Table 1). We applied a stochastic modeling approach, multi‐state models, and analyzed the times spent in each sleep state before transitioning and transition probabilities in and between sleep states. We further applied statistical analysis of sleep monitoring data and sleep questionnaires (ESS, PSQI) from the RADAR‐AD study (Fitbit Charge 3, DREEM) and preliminary data from the ADIS study (MotionWatch8) (Table 1), using a likelihood ratio test with the aim to assess the diagnostic potential of sleep monitoring devices compared to traditional sleep questionnaires.ResultModeling of digital device data showed that preclinial (preAD), prodromal (proAD) and mild‐to‐moderate (mildAD) AD patients spent more time in the light sleep and awake state, and less time in the REM sleep states compared to healthy controls (HC) before transitioning to the next state, showing non‐linear associations between diagnostic stage and sojourn times (Figure 1A). ProAD and mildAD patients had a higher probability to transit to a light sleep phase compared to HC and to subsequently wake up (Figure 1B). Based on our current and partially still preliminary data, only digital sleep monitoring via Fitbit allowed for a separation between HC and preclinical AD at nominal significance (preAD) but findings were not significant when adjusting for multiple testing (Table 2A). A significant distinction between HC and proAD (p < 0.001) as well as between HC and mildAD (p < 0.01) was possible using Fitbit sleep monitoring data, whereas traditional sleep questionnaires were only able to distinguish HC from mildAD (p < 0.05) (Table 2).ConclusionSleep patterns assessed via tested digital devices were able to separate proAD from HC – in case of Fitbit ‐ which was not possible by traditional sleep questionnaires. Digital sleep monitoring has thus the potential to support the early diagnosis of dementia.
Cerebrospinal Fluid Neurofilament Dynamic Profiles Predict Cognitive Progression in Individuals with de novo Parkinson’s Disease
Authors: Sheng Ze‐Hu , Ma Lingzhi , Guo Fan , Liu Jia‐Yao , Tan Lan 
Published: January 2025

AbstractBackgroundNeurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) reflects the severity of neurodegeneration, with its altered concentrations discovered in Parkinson's disease (PD) and Parkinson's disease dementia (PD‐D).MethodA total of 259 people were recruited in this study, including 85 healthy controls (HC) and 174 neonatal PD patients from the Parkinson's Progression Markers Initiative (PPMI). Multiple linear regression and linear mixed effects models were used to examine the associations of baseline/ longitudinal CSF NfL with cognitive decline and other CSF biomarkers. Kaplan‐Meier analysis and log‐rank test were used to compare the cumulative probability risk of cognition progression during the follow‐up. Multivariate cox regression was used to detect cognitive progression in de novo PD.ResultWe found PD patients with mild cognitive impairment (PD‐MCI) was higher than with normal cognition (PD‐NC) in terms of CSF NfL baseline levels (P = 0.003) and longitudinal increase rate (P = 0.034). Both baseline CSF NfL and its rate of change predicted measurable cognitive decline in de novo PD (MoCA, β = ‐0.010, P = 0.011; β = ‐0.0002, P < 0.001, respectively). The predictive effects in de novo PD patients aged > 65, male, ill‐educated (< 13 years) and without carrying Apolipoprotein E ε4 (APOE ε4) seemed to be more obvious and reflected in more domains investigated. We also observed that CSF NfL levels predicted progression in de novo PD patients with different cognitive diagnosis and amyloid status. After an average follow‐up of 6.66 ± 2.54 years, higher concentration above the median of baseline CSF NfL was associated with a future high risk of PD with dementia (adjusted HR 2.82, 95% CI: 1.11‐7.20, P = 0.030).ConclusionOur results indicated that CSF NfL is a promising prognostic predictor of PD, and its concentration and dynamics can monitor the severity and progression of cognitive decline in de novo PD patients.
Chronic treatment with a metabotropic glutamate receptor 2 camelid nanobody accelerates amyloidogenesis in Alzheimer’s disease
Authors: Lafon Pierre‐André , Liu Jianfeng , Perrier Veronique , RONDARD Philippe 
Published: January 2025

AbstractBackgroundImmunotherapy of Alzheimer’s disease (AD) is a promising approach to reducing the accumulation of beta‐amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.Method5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2. Abeta amyloids after this treatment were measured by FRET‐based technologies (HTRF). HTRF techniques were also developed to measure the direct interaction between APP and mGluR2 or mGluR3 at the surface of transfected cells. Other resonance energy transfer techniques were also used to measure the influence of the nanobody on mGluR2 and mGluR3 internalization.ResultEnhancing mGluR2 activity increases Aβ1‐42 peptide production whereas activation of mGluR3 has no effect. We show that such a difference likely results from the directly interaction of APP with mGluR3, but not with mGluR2, that prevents APP degradation to Aβ1‐42 peptides. We then show that chronic treatment with a brain‐penetrating mGlu2 potentiating nanobody of the AD model 5xFAD mice accelerated amyloid aggregation and exacerbated memory deficits, but had no effect in control mice.ConclusionA selective mGluR2 activation exacerbates AD disease development suggesting that therapeutic benefices could be obtained with blockers of this receptor.