bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Internet‐based vs in‐person cognitive interventions on patients with mild to moderate Alzheimer’s disease: A randomized, cross‐over, open‐label trial
Authors: Jung Young Hee H 
Published: December 2023

AbstractBackgroundWe aimed to investigate the effect of Internet‐based and in‐person cognitive interventions on cognition, mood, and activities of daily living (ADL) on patients with mild to moderate Alzheimer’s disease (AD) and examine whether Internet‐based intervention is as effective as the in‐person intervention.MethodWe recruited 52 patients with probable mild AD, of whom 42 completed the trial. We randomly divided participants into intervention and control groups at a 1:1 ratio and statistically compared the neuropsychological test results of the two groups. In addition, patients in the intervention group were randomly assigned to a four‐week Internet‐based or in‐person intervention, with subsequent crossover to the other group for four weeks. We statistically analyzed and compared the neuropsychological test scores between Internet‐based and in‐person interventions.ResultCompared with the control group, the intervention group (Internet‐based and in‐person) showed significantly improved profile in cognition (P<0.001), depression (P<0.001), anxiety (P<0.001) and ADL (P<0.001). In addition, the effect of the Internet‐based intervention on cognition (P = 0.918) and depression (P = 0.282) was not significantly different from that of the in‐person intervention. However, in the Beck Anxiety Inventory (P = 0.009) and Seoul Instrumental Activity of Daily Living (P = 0.023), in‐person intervention was more effective than Internet‐based intervention.ConclusionThis study suggests that both types of cognitive intervention (in‐person and Internet‐based) may be viable supplementary treatments along with approved pharmacological therapy. In terms of cognition and depression, the effect of Internet‐based interventions may not be significantly different from that of in‐person interventions.
Sex Moderates the Association Between Age and Myelin Water Fraction in the Cingulum and Fornix among Older Adults Without Dementia:A Preliminary Study
Authors: Brenner Einat K , Bangen Katherine J. , Clark Alexandra L , Delano‐Wood Lisa , Evangelista Nicole D. , Sorg Scott F , Jak Amy J. , Bondi Mark W. , Deoni Sean C.L. , Lamar Melissa 
Published: December 2023

AbstractBackgroundCognitive decline in normal aging and Alzheimer’s disease (AD) has been associated with changes in cerebral white matter tracts. Although women are at higher risk of developing AD, studies investigating the effect of sex on white matter integrity have been mixed. Decreased white matter integrity in limbic pathways including the fornix and cingulum have been reported in AD although underlying mechanisms and potential sex differences remain understudied. We explored sex as a moderator of the effect of age on myelin water fraction (MWF), a measure of myelin content, in older adults.MethodFifty‐two older adults without dementia (mean age = 72; 61% female) underwent neuropsychological evaluation and 3T MRI at two research sites. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) quantified MWF in three a priori regions of interest including the fornix, cingulum in the hippocampal formation (CGH), and cingulum in the cingulate gyrus (CGC). The California Verbal Learning Test‐Second Edition assessed learning and long‐delay free recall. Separate multiple linear regressions assessed for (1) interactions between age and sex on regional MWF and (2) associations of regional MWF and memory. All models adjusted for APOE e4 allele frequency, vascular risk, and site; the second analysis additionally adjusted for age and sex.Result(1) There was a significant ageXsex interaction for CGC MWF (p = 0.006) and fornix MWF (p = 0.016) (see Figure) but not CGH MWF (p = 0.443). Specifically, for both interactions, in women but not men, as age increased, MWF decreased. (2) Fornix MWF was associated with memory (p = 0.002), but MWF of the two cingulum regions were not (p>0.05). Results did not change when adjusting for hippocampal volume.ConclusionResults suggest that the relationship between age and myelin content of limbic fiber pathways depends on sex, with women but not men showing age‐related decreases. Additionally, and consistent with previous studies, we observed an association between fornix MWF and learning and memory. Understanding sex differences in MWF may facilitate earlier detection of AD risk for women. Longitudinal study with larger samples is needed to further clarify the role sex plays in limbic system myelin integrity and potentially inform interventions.
Does biological sex moderate the association of nature exposure with brain volume? A cross‐sectional analysis of the UK Biobank
Authors: Noseworthy Matt W , Falck Ryan S , Galea Liisa A , Puterman Eli , Handy Todd C , Liu‐Ambrose Teresa 
Published: December 2023

AbstractBackgroundNeighbourhood nature spaces are associated with brain health. Biological sex moderates the associations of various lifestyle and environmental factors with brain health, but it is unclear whether sex moderates associations between nature exposure and brain structure. We thus investigated whether sex moderates the association of residential nature exposure with brain structure in the UK Biobank cohort.MethodsWe conducted a cross‐sectional analysis of the UK Biobank study. We included cognitively healthy participants with available nature exposure data at study entry (2006‐2010) who completed a 3T structural brain MRI (2014‐2021; N = 37,880). Residential nature exposure was estimated as the percentage of land classified as natural environment within 1000m of a participant’s home. We indexed total grey matter volume and total white matter volume, normalized for head size, and hippocampal volume averaged from both hemispheres. We performed linear regressions to assess the independent associations of residential nature exposure and biological sex with brain structure. We then assessed whether sex moderated the association between residential nature exposure and brain structure, and plotted simple slopes to interpret interaction effects. All models adjusted for age, body mass index (kg/m2), educational attainment, income, physical activity (min/day), time spent outdoors (hours/day), smoking status, disability status, Townsend deprivation index, and population density.ResultsAt study entry, mean age was 55 years (SD = 7.53 years) and 53% of participants were female. Average residential nature exposure was 44% (SD = 26%). Every 10% increment in residential nature exposure was associated with 737 mm3 greater grey matter volume (p<0.0001) and 601 mm3 greater white matter volume (p<0.0001). Females had 24,270 mm3 greater grey matter volume (p<0.0001), 9,703 mm3 less white matter volume (p<0.0001), and 223 mm3 less hippocampal volume than males (p<0.0001). Sex moderated the association of residential nature exposure with total grey matter volume, such that every 10% increment in nature exposure attenuated sex differences in grey matter volume by 422 mm3 (p = 0.020) (Figure 1).ConclusionThese results suggest that neighbourhood nature spaces may benefit brain health, and that males may be more sensitive than females to these potential benefits. Longitudinal analyses are needed to verify these findings.
The associations between attentional control and Alzheimer disease biomarkers of tau and neurodegeneration
Authors: Stojanovic Marta , Aschenbrenner Andrew J. , Balota David A. , Schindler Suzanne E. , Ances Beau 
Published: December 2023

AbstractBackgroundAttentional control may be affected in both the preclinical and symptomatic phases of Alzheimer disease (AD). In addition, variability in attentional control has been associated with apolipoprotein E (APOE) genotype, a major genetic modifier of AD risk. This study examined the associations between concurrent attentional control, as well as longitudinal change in attentional control, with AD biomarkers of tau (tau positron emission tomography [PET]) and neurodegeneration (cerebrospinal fluid [CSF] concentrations of neurofilament light chain [NfL]). A secondary goal was to examine whether APOE genotype moderates these relationships.MethodWithin 395 cognitively normal (Clinical Dementia Rating [CDR] = 0) and 70 cognitively impaired (CDR>0) individuals (age range 46‐90 years), attentional control measures (n = 465), PET‐Tau (n = 465), and CSF NfL (n = 370) were obtained. Attentional control was evaluated using composites of accuracy, reaction time, and ex‐Gaussian measures from reaction time analyses, from three attentional control measures, with a primary focus on accuracy and the tau parameter. Linear regression models examined whether attentional control measures were associated with PET‐Tau and CSF NfL cross‐sectionally. Linear mixed models were used to evaluate whether longitudinal trajectories in attentional control predicted levels of PET‐Tau and CSF NfL.ResultWorse concurrent attentional control performance, primarily high tau parameter, was associated with elevated tau‐PET (p = 0.036) and CSF NfL (p = 0.021) in cognitively impaired but not cognitively normal individuals (all p’s > 0.087). Greater decrease in longitudinal attentional control performance, particularly accuracy, was associated with greater tau‐PET (p = 0.031) and NfL (p = 0.011) in the cognitively impaired group but not cognitively normal group (all p’s > 0.325). APOE genotype did not moderate these effects (all p’s > 0.062).ConclusionThe results indicate that cross‐sectional and longitudinal attentional control measures are associated with PET‐Tau and CSF NfL only in cognitively impaired individuals. Future studies are needed to further investigate whether attentional control measures are more sensitive to other AD biomarkers (e.g., CSF tau species), as well as other potential moderators besides APOE genotype, such as medical conditions, mood, and lifestyle factors, including exercise.
Family history and modifiable risk factors in early‐onset Alzheimer’s disease in southern Brazil.
Authors: de Albuquerque Ana Letícia Amorim , Franco Alvaro de Oliveira , Chaves Marcia L Fagundes , Castilhos Raphael Machado 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) represents a burdensome health condition worldwide and has a highly clinical heterogeneity. In particular, the early‐onset presentations may be related to different risk factors and underlying pathological mechanisms. We aimed to compare the frequency of modifiable risk factors/family history of dementia in a sample of AD from a tertiary memory outpatient clinic in Southern Brazil.MethodWe reviewed the clinical data of patients clinically diagnosed with AD at the dementia outpatient clinic at the Hospital de Clínicas de Porto Alegre, Brazil, between 2014 and 2022. We collected sociodemographic, clinical, family history, and the presence of seven modifiable risk factors for dementia: hypertension, diabetes, alcohol abuse, tobacco use, traumatic brain injury, hearing loss and previous psychiatric illness. Differences between early (< 65 years) and late‐onset AD were analyzed by Chi squared and Mann‐Whitney tests, with significance defined as p<0.05. All analyses were made in the R.ResultsA total of 145 patients were evaluated, 96 (66.2%) female, mostly (80.7%) white and median (interquartile range, IQR) of 76 (69‐80) years in the first evaluation. Of these, 40 (27.6%) had early‐onset presentation, with age at onset of 59.3 (52.4 ‐ 63) years. The early‐onset group presented a higher frequency of family history of dementia with an autosomal dominant pattern, 7 (17.5%) vs 0 (p = 0.011), with two patients being diagnosed with PSEN1 mutations, and worse scores in Mini Mental State Examination (p = 0.034) at the first evaluation. The groups did not differ in years of formal education or disease duration at the first appointment. Except for a higher frequency of hypertension in the late‐onset group, 68 (64.8%) vs 18 (45%), p = 0.048, there was no difference in the other risk factors (Table 1).ConclusionIn our sample, the profile of risk factors was similar between early‐ and late‐onset AD presentations, but the early‐onset patients had a higher frequency of autosomal dominant dementia family history. Our results suggest that in our sample the genetic and modifiable risk factors are both associated with early‐onset presentations.
CSF Plasminogen inhibitor 1(PAI‐1) levels are associated with dementia symptoms in Alzheimer disease
Authors: Dlamini Sibonginkhosi L. , Henson Rachel L. , Saef Benjamin A. , Barthélemy Nicolas R. , Hendrix Rachel , Fagan Anne M. , Morris John C , Bateman Randall J. , Cruchaga Carlos , Schindler Suzanne E. 
Published: December 2023

AbstractBackgroundThere are currently excellent fluid biomarkers of brain amyloidosis, including CSF Aβ42/Aβ40 and CSF pT217/T217 (%). However, many individuals with brain amyloidosis do not have symptoms of Alzheimer disease (AD). Biomarkers that are strongly associated not only with brain amyloidosis but also with symptomatic AD would be invaluable tool in clinical trials and clinical diagnosis. We evaluated whether CSF biomarkers in an immunoassay panel added value to existing biomarkers in prediction of cognitive impairment.MethodAn immunoassay panel from Rules Based Medicine was used to measure CSF levels of 52 proteins including plasminogen inhibitor 1 (PAI1). CSF Aβ42/Aβ40 was measured by Lumipulse, and CSF pT217/T217 (%) was measured by an immunoprecipitation‐mass spectrometry assay. Logistic regression and linear models were used to evaluate the association between biomarkers and cognitive status (cognitively unimpaired or symptomatic AD as defined by a Clinical Dementia Rating [CDR] of 0.5 or greater), the Mini‐Mental State Exam [MMSE] score, and CDR Sum of Boxes [CDR‐SB]. Models included the covariates of age, self‐identified gender, and years of education.ResultThe cohort included n = 179 older research participants (average age 73.0 years, standard deviation 6.6 years), of which 47 (26%) had cognitive impairment (CDR>0). Cognitively impaired individuals had higher levels of PAI1 (p = 1.18e‐05) (Fig. 1A). PAI1 levels predicted cognitive status in the entire cohort (p = 4e10−3) and the sub‐cohort with CSF Aβ42/Aβ40 levels consistent with brain amyloidosis (Aβ42/Aβ40<0.0673; p = 0.003). Even when CSF pT217/T217 (%) was included in the model of cognitive status, PAI1 was a significant independent predictor of cognitive status in both the entire cohort (p = 0.005) and the sub‐cohort with brain amyloidosis (p = 0.008) (Fig. 1B). Both the MMSE and CDR‐SB were associated with PAI1 in the entire cohort (p = 1.86e‐07 and p = 5.45e‐07), and the sub‐cohort with brain amyloidosis (p = 2.44e‐05 and p = 4.77E‐05) (Fig. 1C‐D). When CSF pT217/T217 (%) was included in the model, both the MMSE and CDR‐SB remained associated with PAI1 in the entire cohort (p = 8.85e‐06 and p = 3.02e‐05) and the sub‐cohort with brain amyloidosis (p = 0.0001 and p = 0.0003).ConclusionThese results demonstrate that CSF PAI1 is associated with symptomatic AD and adds value to CSF pT217/T217 in predicting AD symptoms.
Cognitive performance is associated with cardiovascular and renal remodeling in young female rats with chronic kidney disease
Authors: Grigorova Yulia N , Santos Carla Rocha Dos , Haghkar Mahdi , Fox Shanaya , Long Jeffrey M , McDevitt Ross A , Morrell Christopher H , Wei Wen , Zernetkina Valentina I , Juhasz Ondrej , Sodhi Komal , Rapp Peter R. , Lakatta Edward G , Fedorova Olga V 
Published: December 2023

AbstractBackgroundThe prevalence of cognitive impairment (CI) and dementia in end‐stage chronic kidney disease (CKD) has been estimated at 30‐60%. Cardiovascular dysfunction accompanies CKD and contributes to CI in humans and animal models. Since CKD occurs more often in females in clinical studies, the aim of this study was to determine whether cardiovascular and renal remodeling is associated with cognitive performance in the female rats with CKD.MethodsFour‐month‐old female Sprague‐Dawley rats were fed with 0.25% adenine diet to induce CKD (n = 19) or a regular control diet (n = 16; CTRL) for 8weeks. Body weight (BW), blood pressure (BP), heart rate (HR), blood urea nitrogen (BUN), sodium, potassium, creatinine, hematocrit, estradiol, and behavioral tests were assessed at the end of the study. The level of anxiety was tested in open field test (OFT) and elevated plus maze (EPM). Spatial memory was tested by the ability to find a hidden platform in Morris water maze (MWM). The data were analyzed by two‐tailed unpaired t‐test and linear regression analysis (LRA).ResultsCKD was associated with higher creatinine and BUN, lower hematocrit, and enlarged hearts, aortae and kidneys vs. CTRL (Table 1). There was no difference in BP, estradiol, sodium and potassium, MWM, OFT and EPM performance between the groups. However, the LRA revealed the association of higher heart weights with a reduced spatial memory and higher anxiety level in both CTRL and CKD (Table 2; Figure 1A,B). The association of higher aortic weight with a reduced spatial memory, and higher kidney weight with higher anxiety levels was demonstrated in CKD only (Table 2; Figure 1C,D). Estradiol was associated with better spatial memory in CKD (LRA: R2 = 0.264; p = 0.04).ConclusionAnxiety‐like behavior and spatial memory were associated with cardiovascular remodeling in young female rats with CKD. We suggest that (1) CKD stimulates development of cardiovascular remodeling, which may affect blood supply of cortex and hippocampus, responsible for anxiety and spatial memory, and (2) estradiol may contribute to a better cognitive performance in the young CKD female rats. The future direction is to investigate whether CKD influences the trajectory of neurocognitive and cardiovascular aging.Supported by NIA/NIH/IRP
Effects of structural and social determinants of health and comorbidities on ethno‐racial differences in ATN plasma biomarkers of Alzheimer’s disease: A HABS‐HD study
Authors: Meeker Karin L. , Ances Beau , Petersen Melissa , Barber Robert , Yaffe Kristine , Zhou Zhengyang , Llibre‐Guerra Jorge J , Zhang Fan , Hall James , Kind Amy J. , Lee Joseph H. , Vardarajan Badri N , Cohen Annie , Mielke Michelle M. , Mapstone Mark , Babulal Ganesh M. , O'Bryant Sid E. 
Published: December 2023

AbstractBackgroundEthno‐racial differences are observed in amyloid (A), tau (T), and neurodegeneration (N) plasma biomarkers of Alzheimer’s disease (AD). In neuroimaging studies, structural and social determinant of health (SSDOH) factors and associated health outcomes may mediate observed racial differences in neurodegeneration markers. However, little is known regarding the potential effects of SSDOH and downstream comorbidities on ethno‐racial differences in AT(N) plasma biomarkers. This study A) assessed potential differences in plasma Aβ42, Aβ40, Aβ42/40, t‐tau, and NfL among Mexican Americans (MA), non‐Hispanic Blacks (NHB), and non‐Hispanic Whites (NHW); B) determined whether SSDOH and comorbidity factors mediate potential ethno‐racial differences in AD plasma biomarkers.MethodData were obtained from the diverse and well‐characterized Health and Aging Brain Study – Health Disparities (HABS‐HD) and included MAs (n = 931), NHBs (n = 258), and NHWs (n = 942). Group differences in AT(N) plasma biomarkers were assessed using analysis of covariance. Age, sex, and cognitive status (Clinical Dementia Rating Scale Sum of Boxes) were included as covariates. Two multiple mediation models were performed with SSDOH (acculturation, chronic stress, income, area deprivation index) and comorbidity factors (body mass index [BMI], blood pressure, diabetes history) as the potential mediators, respectively. Models accounted for age, sex, and cognitive status, assumed nonlinear relationships, and allowed for mediators to be considered simultaneously.ResultPlasma Aβ42 was significantly lower in MAs compared to NHWs (p<0.05). Plasma NfL was significantly higher in MAs compared to NHBs (p<0.01) and for NHWs compared to NHBs (p<0.05). No other significant differences in plasma variables were observed (p’s>0.05). Group differences in plasma Aβ42 were mediated by comorbidity factors (BMI and history of diabetes), but not SSDOH. MAs had greater BMIs and history of diabetes compared to NHWs, both of which were associated with lower plasma Aβ42 levels. SSDOH and comorbidity factors did not mediate group differences in plasma NfL.ConclusionUsing a large and diverse community‐based cohort, we demonstrate that ethno‐racial differences in AD‐specific plasma biomarkers are, in part, due to modifiable health and comorbidity factors. This work informs the conditions that give rise to ethno‐racial differences in plasma ATN biomarkers while highlighting potential ethno‐racial disparities in AD research.
A high‐dimensional incomplete‐modality transfer learning method for early prediction of Alzheimer’s disease
Authors: Ku Dohyun , Zheng Zhiyang , Mao Lingchao , Chen Rui Qi , Su Yi , Chen Kewei , Weidman David , Wu Teresa , Lure Fleming , Lo ShihChung , Li Jing 
Published: December 2023

AbstractBackgroundPrediction of Alzheimer’s disease (AD) risk for individuals with mild cognitive impairment (MCI) provides an opportunity for early intervention. Neuroimaging of different types/modalities has shown promise, but not every patient has all the modalities due to the cost and accessibility constraints. To integrate incomplete multi‐modality datasets, we previously developed a machine learning (ML) model called incomplete‐modality transfer learning (IMTL). We extended the capacity of IMTL to handle high‐dimensional feature sets, namely, HD‐IMTL, to further improve accuracy and robustness.MethodOur dataset included 1319 T1‐MRI scans from MCI patients in ADNI; among them, 1002 had FDG‐PET and 612 had amyloid‐PET. 156 regional volumetric and thickness features were computed from MRI and 83 and 83 regional SUVR features from FDG‐PET and amyloid‐PET, respectively. The dataset is randomly split into training and test sets. The goal of HD‐IMTL was to jointly train 4 ML models to predict MCI conversion to AD in 36 months, with each model based on a certain combination of available modalities, namely, MRI, MRI+FDG, MRI+amyloid, and MRI+FDG+amyloid. These correspond to patient sub‐cohorts that differ in their access to imaging modalities. To handle high‐dimensional features, we employed feature screening to remove uninformative features, performed modality‐wise partial least squares (PLS) to condense remaining features into PLS components, and used correlation tests to select components. To jointly train the 4 ML prediction models, IMTL was used, which is a generative model that uses expectation‐maximization (EM) in joint parameter estimation to facilitate transfer learning. To account for sample imbalance in training, the Synthetic Minority Over‐sampling Technique (SMOTE) was used. The trained models were applied to the test set. 20 training/test splits were repeated and AUCs on the test set were averaged. For comparison, three existing ML models for incomplete‐modality fusion were applied to the same dataset.ResultThe AUCs by HD‐IMTL were 0.802, 0.840, 0.868, and 0.880 for sub‐cohorts with MRI, MRI+FDG, MRI+amyloid, and MRI+FDG+amyloid, respectively. The AUCs by existing methods were lower, with ranges of 0.749‐0.793, 0.769‐0.826, 0.816‐0.863, and 0.832‐0.868.ConclusionHD‐IMTL demonstrated high accuracy in predicting MCI conversion to AD for patients with varying access/availability of imaging modalities.