bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker evidence of neurodegeneration in chronic kidney disease, in a general population
Authors: Dittrich Anna , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Zettergren Anna , Simrén Joel , Shams Sara , Machado Alejandra , Westman Eric , Schöll Michael , Skoog Ingmar , Kern Silke 
Published: June 2023

AbstractBackgroundProgressive decline in cognition and renal function are both related to ageing. The estimated global prevalence of dementia was 55 million people in 2019, a number expected to increase to 139 million by 2050. Furthermore, chronic kidney disease (CKD) is the second fastest growing cause of death globally. Few studies have examined the link between these conditions. In this study, we examine CKD and estimated glomerular filtration rate (eGFR) in relation to plasma neurofilament light protein (P‐NfL) and volumetric magnetic resonance imaging (MRI) measures of Alzheimer’s disease‐specific and general neurodegeneration.MethodUsing a cross‐sectional design, 744 participants from the Gothenburg H70 Birth cohort 1944 study, conducted in 2014‐2016, underwent MRI examination and blood draws. Plasma NfL concentration was measured using a Single molecule array (Simoa) assay. eGFR was calculated from creatinine and used for CKD diagnosis. CKD was defined as an estimated glomerular filtration rate below 60 mL/min/1.73 m2. Measurements of biomarker evidence of neurodegeneration were compared between participants with and without CKD. Correlations were also performed against eGFR. A logistic regression model adjusting for known risk factors for CKD was performed.ResultP‐NfL was significantly higher in participants with CKD (p<0.001). No difference was seen in any MRI variables. Only P‐NfL correlated with eGFR (R = ‐0.25, p<0.001), and there was a significant correlation both in participants with and without CKD (R = ‐0.44, p<0.001 and R = ‐0.18, p<0.001 respectively). Furthermore, in a logistic regression model, P‐NfL was a significant predictor of CKD independent of known risk factors including age, sex, education, smoking, hypertension, diabetes, BMI, fasting glucose, LDL‐cholesterol, CRP, and homocysteine (OR (CI); 3.231 (1.743: 5.990), p<0.001).ConclusionOur observations suggest that neurodegeneration measured as P‐NfL is a predictor of CKD, independent of hypertension and diabetes. The origin of NfL, and the potential influence on the utilization of P‐NfL as a marker of neurodegeneration in individuals with CKD, should be assessed in future studies.
Unknown treatment effects of donepezil in Alzheimer’s disease: Network analysis of three double‐blind randomized, placebo‐controlled, clinical trials
Authors: Rotstein Anat , Levine Stephen Z , Samara Myrto , Yoshida Kazafumi , Goldberg Yair , Cipriani Andrea , Iwatsubo Takeshi , Leucht Stefan , Furawaka Toshiaki A 
Published: June 2023

AbstractBackgroundPsychometric network analysis is an alternative theoretically‐driven analytic approach that has the potential to conceptualize cognitive impairment in Alzheimer’s disease differently than was previously assumed and consequently detect unknown treatment effects.MethodBased on individual participant data, extracted from three double‐blind, randomized placebo‐controlled clinical trials, psychometric networks were computed on observed Alzheimer’s Disease Assessment Scale Cognitive Subscale scores at baseline (N = 1,554) and on predicted change scores at 24 weeks of follow‐up for participants who received donepezil (N = 797) or placebo (N = 484).ResultA novel conceptualization of cognitive impairment in Alzheimer’s disease was displayed through the baseline network, that had 90% (n = 27) positive statistically significant (p<0.05) associations, and a most central aspect of ideational praxis. Following 24 weeks, treatment effects emerged via the differences between the change networks. The donepezil change network had more statistically significant (p<0.05) positive associations and a higher global strength (n = 15; S = 1.22; p = 0.03), than the placebo network (n = 8; S = 0.57), suggesting that for those who were treated with donepezil cognition is a more unified construct. Less for those given placebo. The main aspects of change in cognitive impairment were comprehension of spoken language for the donepezil network and spoken language ability for the placebo network, suggesting that comprehension of spoken language is most sensitive to pharmaceutical interventions.ConclusionOverall, psychometric network analysis presents a new conceptualization of cognitive impairment in Alzheimer’s disease, points to previously unknown treatment effects and highlights well‐defined aspects that may translate into future treatment targets.
Determining whether sex and zygosity modulates the association between ApoE4 and psychosis in a neuropathologically‐confirmed Alzheimer’s disease cohort
Authors: Fischer Corinne E. , Valcic Mila , Kim Julia , Fornazzari Luis R , Churchill Nathan W , Schweizer Tom A. , Munoz David G. 
Published: June 2023

AbstractBackgroundIndividuals with the APOE ε4 allele (ApoE4) have an increased risk of developing Alzheimer’s disease (AD) compared to individuals with the more common ε2 or ε3 alleles. Previous work by our group found that female ApoE4 homozygotes with Lewy body (LB) pathology were more likely to experience psychosis compared to female ApoE4 non‐carriers, whereas in males there was no dose‐dependent difference (Kim et al., 2017). The objective of this study was to refine our previous findings by adjusting for covariates (age, education, MMSE scores).MethodThe patient cohort was obtained from the National Alzheimer’s Coordinating Center (NACC). Demographics, APOE genotype, LB pathology, and Neuropsychiatric Inventory (NPI) data was gathered in individuals with neuropathologically‐confirmed AD (n = 1,241). Patients were considered psychotic if they scored positively for delusions and/or hallucinations on the NPI. Two cohorts were extracted, those with LB pathology (LB(+)) and those without (LB(‐)). Within each cohort, patients were classified as E4(‐), E4, or E44 based on the number of APOE ε4 alleles they carried (0, 1, 2, respectively), and stratified by sex. Binary logistic regression was used to predict the relationship between ApoE4 status and sex on presence of psychosis.ResultIn the LB(+) group, female ApoE4 homozygotes were significantly more likely to experience psychosis compared to female ApoE4 non‐carriers (p = .003). The significant effect remained after adjusting for covariates (p = .027). There was no significant association between ApoE4 and presence of psychosis in males. In the LB(‐) group, there was no significant association between ApoE4 and presence of psychosis in either sex. There was no significant effect in female nor male ApoE4 heterozygotes, with or without LB pathology.ConclusionSex and zygosity modulate the effect of ApoE4 on psychosis in a cohort of neuropathologically‐confirmed AD patients, specifically, that the effect of having 2 ApoE4 alleles on presence of psychosis is limited to female ApoE4 homozygotes with LB pathology. These findings reveal a cohort of AD patients that appear to be particularly vulnerable to developing psychosis.References: Kim, J., Fischer, C.E., Schweizer, T.A., & Munoz, D.G. (2017). Gender and pathology‐specific effect of Apolipoprotein E genotype on psychosis in Alzheimer’s disease. Current Alzheimer Research, 14(8), 834‐840.
Longitudinal trajectories of dietary quality and cognitive functions in Chinese older adults: The Taiwan Initiative for Geriatric Epidemiological Research (TIGER) cohort study
Authors: Chen Ling‐Wei , Chen Jen‐Hau , Chiou Jeng‐Min , Chen Ta‐Fu , Chen Yen‐Ching 
Published: June 2023

AbstractBackgroundDietary factors influence cognitive functions, but most previous studies were conducted in Western settings and assessed diet only once. Trajectory analysis of diet measured at multiple timepoints can track changes in diet and identify subpopulations requiring more intervention efforts. We thus assessed associations between dietary trajectories and cognitive functions in an understudied Asian elderly population.MethodThe TIGER study involves non‐demented community‐dwelling participants aged ≥65 years recruited between 2011‐2013. Dietary intakes were assessed using a food frequency questionnaire during baseline and 4th‐ and 6th‐year follow‐ups. Modified Alternative Healthy Eating Index (mAHEI) scores (energy‐adjusted using the residual method) were generated at each timepoint to reflect diet quality. Longitudinal trajectories of dietary quality were derived using latent growth mixture modelling. The Montreal Cognitive Assessment—Taiwanese version was used to assess global cognition for outcomes. Cognitive functions (baseline‐normalized z‐scores) of four cognitive domains, i.e., memory, attention, executive function, and verbal fluency, were also assessed. Associations between trajectories of dietary quality and cognitive functions were assessed using linear regressions, adjusting for important covariates including sex, apolipoprotein (APOE) e4 status, baseline age, body mass index (BMI), and depressive symptoms.ResultIncluded participants (n = 356) were 54.2% female, had a mean age of 71.6 years, and a mean BMI of 23.8 kg/m2 at baseline. The overall mean mAHEI scores were close to 37 (out of 70 possible) at all three time points. Three trajectories of dietary quality, namely 1) ‘increasing’, 2) ‘decreasing’, and 3) ‘stable‐high’ were identified and deemed optimal considering fit indices and interpretability. Compared with ‘stable‐high’ dietary quality trajectory, the ‘increasing’ trajectory was associated with worse memory performance (adjusted‐β = ‐0.424; 95% CI: ‐0.679, ‐0.169; P = 0.001) whereas the ‘decreasing’ trajectory was associated with worse performance for the verbal fluency domain (adjusted‐β = ‐0.342; 95% CI: ‐0.653, ‐0.030; P = 0.031). No other significant associations were observed.ConclusionMaintaining a stable‐high dietary quality trajectory over time is associated with better cognitive functions among Taiwanese older adults. Since there is much room for dietary improvement in this Taiwanese population, interventions to promote and sustain better dietary quality over time can have substantial impacts on their cognitive functions.
Association between olfactory function and cognitive impairment in dementia‐free older adults in Taiwan: A longitudinal cohort study
Authors: Wang Mu‐Cyun , Chen Yen‐Ching , Chiou Jeng‐Min , Chen Ta‐Fu , Chen Jen‐Hau 
Published: June 2023

AbstractBackgroundThe olfactory impairment could be one of the earliest signs of cognitive impairment. However, limited studies have evaluated olfactory function and cognitive domains in Asian older adults. This study aimed to relate olfaction with global and domain‐specific cognition in Taiwan’s community‐dwelling, non‐demented older adults.MethodThis cohort study is part of the Taiwan Initiative for Geriatric Epidemiological Research, including 310 non‐demented older adults between 2015‐2019 with two repeated measures on cognitive function. Global and domain‐specific (memory, executive function, attention, and language) cognition were assessed by the Taiwanese version of Montreal Cognitive Assessment (MoCA‐T) and a battery of neuropsychological tests, respectively. The Sniffin' Sticks‐Odor Identification Test (SS‐OIT) was utilized to identify impaired olfaction. The generalized linear mixed model was used to examine the association of SS‐OIT with cognitive function over time, after adjustment for age, sex, years of education, apolipoprotein E ε4 status, presence of depression, sleep quality, chronic respiratory diseases, smoking, practice effect and follow‐up time. Subgroup analyses were also conducted.ResultBetter olfactory identification ability (i.e., increased SS‐OIT score) was associated with better performance of global cognition (MoCA‐T: β = 0.14, 95% confidence interval = 0.05‐0.24), memory (logical memory ‐ immediate and delayed theme and free recall: β = 0.06 to 0.09), executive function (trail making test‐A: β = 0.05 for baseline, ‐0.03 for interaction with follow‐up years), and verbal fluency (β = 0.08). Anosmia (SS‐OIT score ≦8) was associated with impaired memory [the lowest tertile (T1) vs. higher tertiles (T2+T3), adjusted odds ratio (aOR): 2.40 to 3.06], and verbal fluency (T1 vs. T2+T3, aOR = 2.39). After stratified analyses, the associations above remained significant in apolipoprotein E ε4 non‐carriers (MoCA‐T: β = 0.19; memory: β = 0.08 to 0.11; verbal fluency: β = 0.08), older adults without respiratory diseases (MoCA‐T: β = 0.14; memory: β = 0.06 to 0.10; verbal fluency: β = 0.10), and older adults without depression (MoCA‐T: β = 0.14; memory: β = 0.06 to 0.09; trail making test‐A: β = 0.04 for baseline, ‐0.02 for interaction with follow‐up years; verbal fluency: β = 0.09).ConclusionImpaired olfactory identification is associated with poor global or domain‐specific cognition in non‐demented older adults. Further research is required to validate our findings and clarify the underlying mechanism between anosmia and cognitive impairment.
Patterns of disruption of white matter integrity in mild cognitive impairment and Alzheimer’s disease with and without vascular comorbidities
Authors: Konwar Srijan 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) has been primarily been considered a grey matter disease. Recent studies, however, indicate the presence of white matter abnormalities in AD. This study’s aim was to investigate the patterns of white matter disruption in people with mild cognitive impairment (MCI) and AD dementia with vascular comorbidities (obesity, diabetes and hypertension).MethodDiffusion Tensor Imaging (DTI) was used to appraise white matter integrity using diffusion indices such as axial diffusivity (AxD) and mean diffusivity (MD). Participants were stratified according to presence or absence of vascular comorbidities and group status (controls n = 13, MCI n = 13 and AD n = 13). The vascular comorbidities were binarized into High Risk (either one or more vascular risks) or Low Risk (no vascular risks). Each pathological group was compared to Low‐Risk controls who served as the reference sample. Both groups were matched by age. For each of the group comparisons, there were 13 participants for each condition with the exception of the Low‐Risk AD group comparison where there were only 7 participants for both conditions. Between group differences in diffusion indices were measured using voxel‐wise whole brain approach using tract based spatial statistics (TBSS). A non‐parametric unpaired T‐Test was conducted between each group and the reference sample while controlling for location (site of recruitment), total intracranial volume and years of education.ResultThe results indicate that vascular comorbidity primarily affects the right projection fibres, forceps major, posterior areas of the corpus callosum such as the splenium as well as right fornix/stria terminalis. In the absence of comorbidities, in MCI and AD white matter is compromised in commissural fibres such as genu and body of the corpus callosum along with forceps minor.ConclusionThese results suggest that microstructural differences are more visible than macrostructural changes in AD. The results suggests that late myelinating fibres are more prone to damage to both neurodegeneration and vascular risks. In addition, the splenium of the corpus callosum is affected at a more severe stage in AD but is also affected by the presence of vascular risks.
White matter hyperintensities in strategic tracts for cognitive impairment: A multicenter lesion‐symptom mapping study in 3525 memory clinic patients
Authors: Coenen Mirthe , Biesbroek J. Matthijs ,   Meta VCI Map consortium
Published: June 2023

AbstractBackgroundWhite matter hyperintensities (WMH) due to small vessel disease (SVD) are associated with dementia risk. Previous studies suggest that the cognitive impact of WMH depends on location. However, these studies were potentially limited by moderate brain lesion coverage. We aimed to identify strategic WMH locations for cognitive impairment in memory clinic patients by performing a large‐scaled multicenter study providing unprecedented lesion coverage.MethodIndividual patient neuropsychological and MRI data from eleven memory clinic cohorts were harmonized. Voxel based lesion symptom mapping‐ (VLSM) and region of interest (ROI) based analyses were performed to identify strategic WMH locations for four cognitive domains (attention and executive functioning, information processing speed, verbal memory, and language). A strategic WMH score was calculated based on quartiles of WMH volumes in the strategic white matter tracts and was related to cognition using Lasso regression, accounting for multicollinearity, and multivariable linear mixed models.ResultThe combined sample consisted of 3525 patients (age: 71.6 ± 9.0 years; 49.9% female) (Table 1). The WMH prevalence maps are shown in Figure 1. In the merged study sample, 63.0% of the supratentorial white matter was affected by WMH in ≥5 patients and could be included in the VLSM analysis. In the VLSM analysis, statistically significant voxels were found for each of the four cognitive domains, after correction for total WMH volume and multiple testing. These voxels were mostly located in the left and right anterior thalamic radiation and the forceps major. Independent ROI based analysis confirmed these strategic tracts and additionally identified the left inferior fronto‐occipital fasciculus as significant tract (Table 2). The strategic WMH score was significantly associated with lower performance on attention & executive functioning (B‐0.146; p<0.001), information processing speed (B‐0.090, p = 0.023), language (B‐0.124, p = 0.003), and verbal memory (B‐0.128, p<0.001), independent of total WMH volume, age, sex, education, brain parenchymal fraction, and study site.ConclusionThis large multicenter study provides strong evidence that the cognitive impact of WMH in memory clinic patients depends on location and identified four significant white matter tracts. With further refinement, WMH location might become a useful diagnostic biomarker for SVD‐related cognitive impairment.
System dynamics model on the interplay between social health and dementia
Authors: Lenart‐Bugla Marta 
Published: June 2023

AbstractBackgroundDementia, as a multi‐factorial condition with complex underlying mechanisms, demands a comprehensive approach of prevention and treatment, especially, focused on psychosocial interventions. This work is aimed at presenting a system dynamics (SD) model on the role of social health in the trajectory from cognitive health to dementia.MethodWe used a staged approach for building a SD model, presenting SH‐cognition bidirectional relationship, based on (1) systematic literature review on factors related to cognitive decline, (2) Group Model Building sessions with interdisciplinary experts, (3) iterative way of integrating results from epidemiological, multi‐national cohort studies, (4) ongoing revisions of SH concept via structured discussions between experts. This knowledge synthesis was harmonized and transformed into a causal pathway model in Kumu program (https://kumu.io/).ResultThe SD model presents maps on three levels: health domains, concepts with dimensions, markers. The last is a representation of interaction and feedback mechanisms between social health and cognition through three pathways: Physiological, psychological, and health‐behavioral, and through, so called ‘cognitive reserve & brain reserve’. Each marker is described with definitions and level of evidence (from expert’s knowledge to systematic review). The outcome shows that multiple SH factors contribute to cognitive decline and dementia (e.g. loneliness, being single), being risk factors, and other serve as protective factors (e.g. high social frequency, social support). In return, presence of dementia symptoms influences SH, f.ex. making the individual more dependent on social network, or being less satisfied with social ties.ConclusionThe SD model elucidates dynamic and complex relationships between dementia and SH, which might serve a role of a reserve in the context of changed roles in social life of an individual with dementia. This novel representation will be translated into key elements and targets for recommendations for interventions, both for prevention and for improved dementia care.
White matter lesions predominantly located in deep white matter represent embolic etiology rather than small vessel disease
Authors: Jung Young Hee H 
Published: June 2023

AbstractBackgroundIndividuals with cerebral small vessel disease (CSVD) usually have both periventricular and deep white matter hyperintensities (dpWMH). However, we often encounter individuals whose WMH lesions are mainly located in the corticomedullary or deep white matter with minimal periventricular WMHs (dWMH). We aimed to determine if the dWMH pattern could be attributed to embolic etiologies.MethodsWe retrospectively recruited participants who had undergone comprehensive dementia evaluation, agitated saline contrast echocardiography, and brain MRI. The participants were classified into two groups according to WMH distributions, the dWMH (WMHs in deep and corticomedullary area, with minimal periventricular WMHs) and the dpWMH (mainly periventricular WMHs with or without deep WMHs) groups. We hypothesized that dWMH is more likely associated with embolism, whereas dpWMH with CSVD. We compared the clinical characteristics, WMH distributions, and the positive rate of agitated saline study between the two groups.ResultsOf the 90 participants, 27 fulfilled the dWMH criteria and 12 met the dpWMH criteria. The dWMH group was younger (62.2±7.5 vs 78.9±7.3, p<0.001), and had a lower prevalence of hypertension (29.6% vs. 75%, p = 0.008), DM (3.7% vs. 25%, p = 0.043), and hyperlipidemia (33.3% vs. 83.3%, p = 0.043) than the dpWMH group. Regarding deep white matter lesions, the number of small lesions (<3 mm) was higher in the dWMH (10.9±9.7) than the dpWMH (3.1±6.4) group (p = 0.008), and WMHs were predominantly distributed in border‐zones of major cerebral arteries and corticomedullary areas.Most importantly, the positive rate of agitated saline was higher in the dWMH than the dpWMH group (81.5% vs. 33.3%, p = 0.003).ConclusionsThe dWMH group with younger age, fewer cardiovascular risk factors showed more border‐zone distributions, and higher positivity of agitated saline test than dpWMH group, indicating that WMH distributions mainly in the corticomedullary or deep area with minimal periventricular WMH lesions suggest embolic etiologies.