bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Reducing Sedentary Behavior Duration by Increasing Physical Activity, on Cognitive Function, Brain Function and Structure Across the Lifespan: A Systematic Review
Authors: Feter Natan , Pindus Dominika 
Published: January 2025

AbstractBackgroundNo study has synthesized evidence from randomized controlled trials (RCTs) testing the acute and chronic effects of reallocating sedentary time (ST) to physical activity (PA) on cognitive and brain health across the lifespan.MethodSeven academic databases were systematically searched on October 26, 2022, with an updated search on June 23, 2023. Inclusion criteria encompassed RCTs published in English involving healthy participants aged ≥ 4 years. Acute (lasting 3 hours to 13 days) and chronic (lasting ≥ 2 weeks) interventions aiming to reduce ST and/or prolonged ST by reallocating ST to PA to improve cognition, brain function, and structure were included. Two independent assessors evaluated the study quality using the Risk of Bias 2.0 tool.ResultWe included 22 trials (n = 1,166) investigating acute (18 studies) and chronic (4 studies) effects on cognition (21 studies) and brain function (5 studies). No study investigated brain structure. Most studies included adults aged 18‐64 years (63.9%), followed by children and adolescents (4‐17 years) (27.3%) and older adults (≥65) (9.0%). Inconclusive evidence exists regarding the impact of reallocating ST to PA on brain function and cognition, attributed to the high risk of bias, limited number of studies, and diverse exercise protocols. However, emerging neurofunctional findings from a single chronic study suggest that relative to prolonged ST, introducing one bout of high‐intensity PA on most days enhanced neural efficiency of the hippocampus and parahippocampal gyrus during an episodic memory task in young adults. Interrupting ST with light PA bouts also acutely improved cerebrovascular function in young adults (1 out of 3 studies). The positive cognitive effects of acutely interrupting prolonged ST with PA were selective to inhibitory control (3 out of 6 studies) and mental flexibility (2 out of 5 studies), with largely null findings on other cognitive outcomes and chronic interventions.ConclusionThe evidence on the acute and chronic effects of reallocating ST to PA on brain function and cognition remains inconclusive with no studies measuring brain structure. However, specific studies suggest that reallocating ST to PA may chronically enhance hippocampal function and acutely improve inhibitory control, mental flexibility, and cerebrovascular function.
Baseline Predictors of Study Discontinuation in a Preclinical Alzheimer’s Disease Clinical Trial
Authors: Raman Rema , Hussen Kedir , Donohue Michael C. , Langford Oliver , Molina‐Henry Doris P. , Aisen Paul S. S. , Sperling Reisa A , Grill Joshua D ,   the A4 Study Team
Published: January 2025

AbstractBackgroundParticipant dropout from study treatment in a clinical trial can leave a trial underpowered, produce bias in statistical analysis, and limit interpretability of study results. Retaining participants in clinical trials for the full study duration is therefore as important as participant recruitment. This analysis aims to identify the baseline characteristics of participants who discontinued during the blinded phase of one of the first and largest preclinical AD trial completed to date, the Anti‐Amyloid treatment in Asymptomatic AD (A4) Study.MethodThe sample consisted of all A4 trial randomized participants followed for 4.5 years through the COVID‐19 pandemic. Baseline demographic (with age centered at 73 years), clinical, amyloid PET and genetic predictors of study discontinuation were evaluated using a univariate generalized linear mixed model (GLMM), with study discontinuation status as the binary outcome, each predictor as a fixed effect, and site as a random effect to account for differences among study sites in the trial. Characteristics significant at p<0.10 were then included in a multivariable GLMM.ResultOf 1169 randomized participants, 339 (29%) discontinued from the trial (median follow‐up time: 759 days). Main reasons included participant unwilling to continue (55.8%) and adverse events (18.9%). From the multivariable analysis, the two main predictors of study discontinuation were baseline State‐Trait Anxiety Inventory (STAI) scores (OR = 1.07 [95%CI = 1.02; 1.12]; p = 0.0024) and age (OR = 1.06 [95%CI = 1.03; 1.09]; p<0.0001). Participants with a family history of dementia (OR = 0.75 [95%CI = 0.55; 1.01]; p = 0.0627) and APOEe4 carriers (OR = 0.79 [95%CI = 0.6; 1.04]; p = 0.0941) were less likely to discontinue from the study, with the association being marginally significant. In these analyses, sex, race and ethnic underrepresented group (combined due to small sample sizes), cognitive scores and amyloid/tau PET scores were not associated with study dropout.ConclusionOlder participants and those with higher levels of anxiety at baseline were more likely to discontinue while those who had a family history of dementia or were APOEe4 carriers were less likely to dropout. Continued analyses aim to identify post‐baseline and longitudinal predictors of attrition in this preclinical AD trial.
Combination therapies targeting AD risk factors delay cognitive decline over 10 years in Alzheimer’s patient
Authors: Torrandell‐Haro Georgina , Shang Yuan , Vitali Francesca , Brinton Roberta Diaz 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) is a complex neurodegenerative disease characterized by multiple etiologies that remains without a cure. Diabetes, dyslipidemia, hypertension, and inflammation are well‐known risk factors for AD, and FDA‐approved therapeutics for these conditions have been associated with a reduced risk of developing AD. This study aims to evaluate the impact of diabetes medications (DBMD), lipid‐lowering (LIPL), antihypertensive (AHTN), and non‐steroidal anti‐inflammatory (NSD) therapeutics, alone or combined, on cognitive performance in an AD population.MethodThis study used the National Alzheimer’s Coordinating Center (NACC) database that includes longitudinal records of diagnoses, prescriptions, and cognitive performances of AD patients across the United States. A subset of 7,653 AD patients (mean age 74.1 years old) with mean baseline cognitive scores representative of a state of mild dementia was selected from 48,605 NACC participants. Change from baseline scores for Clinical Dementia Rating Sum of Boxes (CDR‐SB) and Mini‐Mental State Examination (MMSE) were compared between non‐treated and treated patients over 10 years. Differences in cognitive performance were also evaluated based on sex and APOE genotype.ResultThe quadruplet combination of DBMD+LIPL+AHTN+NSD resulted in a 44% and 35% (MMSE/CDR‐SB) delay in cognitive decline at 5 years and 47% and 35% (MMSE/CDR‐SB) delay at 10 years. The cognitive performance of AD patients treated with monotherapy of LIPL, AHTN, or NSD as assessed by MMSE and CDR‐SB was significantly delayed (10% to 24%) compared to untreated patients at 10 years. Moreover, the data indicated additive and synergistic efficacy in slowing the rate of cognitive decline with combination therapy where slower cognitive decline was observed in patients treated with an incremental number of medications. Moreover, our findings revealed sex‐ and APOE genotype‐specific impact on cognitive performance for each treatment combination, where females and APOE4 exhibited the greatest cognitive benefit of combination therapy.ConclusionCombination therapies targeting AD risk factors significantly slowed cognitive decline in AD patients at a magnitude comparable to or greater than beta‐amyloid immunomodulator interventions. Our findings strongly support combination precision medicine, tailored to address multiple AD risk factors within specific subpopulations based on sex and APOE genotype.
Education correlate with hippocampus volumes in African American males but not in females
Authors: Esiaka Darlingtina , Abner Erin L. , Powell David K , Jicha Gregory A , Jiang Yang 
Published: January 2025

AbstractBackgroundPrior research shows that education is a protective factor against cognitive decline. Education can contribute to cognitive reserve and influence the formation and efficiency of neural networks in the brain. Brain volume, particularly changes in specific brain regions, such as the hippocampus, amygdala, and precuneus, plays a significant role in cognitive decline. Reduced brain volumes are associated with impairments in episodic memory and decline in higher‐order cognitive processes, a hallmark and predictive marker seen in conditions like Alzheimer’s disease. Research also suggests that brain volume measures serve as predictive markers for cognitive decline and may aid in the early detection of neurodegenerative diseases. The current study explored sex differences in the association between education and brain volumes in older Black Americans.MethodData from 38 African American participants (Mage = 72.81, SD = 8.43; 26 females) were derived from the University of Kentucky Alzheimer’s Disease Research Center (UK‐ADRC) cohort, and their years of education ranged from 10‐21 years (M = 15.14, SD = 2.99). The participants completed a series of tests, including a review of health history, physical and neurological exams, neuropsychological testing, and MRI scans in accordance with procedures at UK‐ADRC.ResultWe found that, in African American males, higher years of education were significantly associated with increased volume in the left hippocampus (r = .801, p <.01) and right hippocampus (r = .834, p <.01). Results also showed a trending negative association between higher levels of education and right amygdala (r = ‐.612, p = .06) in African American males. We observed no association between education and brain volumes in African American females.ConclusionOur findings suggest that contextual differences may interact with educational attainment to impact brain development in males versus females. Also, educational experiences may have varying effects on neuroplasticity, and brain volume changes over the lifespan, influencing cognitive aging differently in males and females. Studying how education interacts with brain volumes in males versus females can contribute to a more nuanced understanding of the relationship between education and cognitive decline. This knowledge can inform preventive measures and interventions sensitive to the unique needs and vulnerabilities of both males and females.
The FCI‐SF predicts Alzheimer’s disease related cognitive changes
Authors: Zak Ella , Schlickmann Thomas Hugentobler , Zimmer Eduardo R. , Bastiani Marco De , Bieger Andrei , Borelli Wyllians Vendramini 
Published: January 2025

AbstractBackgroundRecognizing Alzheimer’s disease (AD) early is essential for enhancing patient outcomes. Therefore this research focused on exploring indicators of AD by investigating the role of declining financial capacity (FC) in predicting objetive cognitive impairment (OCI).MethodWe analyzed participants without OCI in Mini‐mental state examination (MMSE, Table 1) or Clinical Dementia Rating‐Sum of Boxes (CDR‐SB, Table 2) scores from the ADNI database. They had a prior completed Financial Capacity Instrument‐Short Form (FCI‐SF). Cox proportional hazard models were used to evaluate how different FCI‐SF scores influence the risk of transitioning to MMSE and CDR‐SB scores that indicate OCI and the timeframe involved. The analyses used the survminer and survival packages in R and corrected for age, gender, diagnose, race, education as covariates (p<0.05).ResultParticipant mean age (SD) for MMSE analysis was 71.3 (±6.6) years (50.8% female). The low FCI‐SF score group (HR = 25.67, 95% CI = 6.232‐105.737) was more likely to convert under the cutoff score for MMSE in the future compared to the high group. Compared to the low group, the high (HR = 0.0389, 95% CI = 0.00945‐0.1605) and mid group (HR = 0.0797, 95% CI = 0.0438‐0.1449) exhibited a lower conversion likelihood.Mean age for CDR‐SB analysis was 71.1 (±6.4) years (51.8% female). The low group had an increased conversion risk (HR = 9.8128, 95% CI = 3.5171‐27.378) compared to the high group. The high (HR = 0.1019, 95% CI = 0.0365‐0.2843) along with the mid group (HR = 0.1993, 95% CI = 0.1207‐0.3289) had a decreased likelihood to convert compared to the low group.Converters from the MMSE analysis had a mean (SD) examination time of 2.1 (±1.2) years prior to the conversion. CDR‐SB converters had mean (SD) of 2.2 (±1.3) years. Individuals with higher education had lower conversion likelihood.ConclusionA low FCI‐SF score can help predict future MMSE and CDR‐SB outcomes. According to Cox models, individuals with lower FCI‐SF scores have an increased risk of transitioning to MMSE and CDR‐SB scores that indicate OCI.
The impact of music experience on hippocampal subfields and cognitive function in older adults at risk for dementia
Authors: Espinosa Nicole , Almgren Hannes , McKinnon Andrew C , Naismith Sharon L 
Published: January 2025

AbstractBackgroundIt has been argued that engaging in musical activities throughout one's lifespan can promote neuroplasticity and protect against age‐related cognitive decline. Most of the research on this topic has been performed on professional musicians; however, general music experience across the lifespan may also have a protective effect on cognitive performance and brain health in non‐professional musicians. This study investigates the effects of lifetime music experience on hippocampal subfield grey matter (GM) volumes and memory and executive functioning in older adults at risk of dementia.Method168 individuals aged ≥50 years (mean age = 68.83, females = 67.9%, MMSE = 28.99 ) with (n = 87) and without (n = 81) a history of music experience and with a MMSE ≥24 were recruited from a memory clinic. Participants underwent tests of memory (Logical Memory subtest of the Wechsler Memory Scale‐III and the Rey Auditory Verbal Learning Test; RAVLT) and executive functioning (the DKEFS Colour Word Interference Test condition 3; CWIT, and the Trail Making Test part B; TMT), as well as MRI data acquisition of the hippocampus (T1 and high‐res hippocampus T2) from which the CA1, dentate gyrus (DG) and subiculum were computed (and corrected for intracranial volume) using the automated segmentation of hippocampal subfields (ASHS) software. Multiple Pearson’s partial correlational analyses adjusting for age were carried out to examine the association between music experience, hippocampal subfields, and cognition. All statistical tests were two‐tailed (alpha = 0.05).ResultPearson's partial correlation coefficient indicated that music experience was associated with higher scores in both tests of executive functioning, the TMT (r = 0.172; p = 0.028) and CWIT (r = 0.196; p = 0.012). However, memory was not significantly correlated with music experience. There were no differences in hippocampal subfield volumes between those who did and did not have musical experience.ConclusionOlder adults with music experience showed significantly better executive functioning compared to those without. However, this improvement was not associated with any differences in hippocampal subfield volumes. Further research is needed to fully understand the effect of music experience on other MRI markers.
Cognitive reserve: Investigate the efficacy of resistance training on cognitive reserve in older adults with subcortical ischemic vascular cognitive impairment
Authors: Gu Yi , Hsu Chun Liang , Silva Narlon Cassio Boa Sorte , Tam Roger , Alkeridy Walid Ahmed , Lam Kevin , Liu‐Ambrose Teresa 
Published: January 2025

AbstractBackgroundSubcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. White matter hyperintensities (WMH) secondary to SIVCI often result in impaired executive function. Cognitive reserve is a property of the brain that allows for preserved cognitive performance given brain injury or disease. In an unpublished cross‐sectional study, we found the strength of intra‐network connectivity in fronto‐executive network (FEN), fronto‐parietal network (FPN) and default mode network (DMN) moderated the relationship between WMH and executive function in older adults with SIVCI. Thus, these networks may be involved in cognitive reserve. Exercise is hypothesized to contribute to cognitive reserve. We explored the effect of resistance training (RT) on functional connectivity (FC) in FEN, FPN, and DMN, as well as executive function, in older adults with SIVCI.MethodIn a 12‐month randomized controlled trial that randomized adults with SIVCI to either 2x/week of RT or 2x/week of balance and tone training (BAT; control). Resting‐state functional MRI was collected from a subset of 29 participants (RT = 14; BAT = 15) at baseline and trial completion. FC of FEN, FPN, and DMN was quantified using priori‐selected region‐of‐interest masks. Executive function was measured by Trail Making Test (TMT), Digit Symbol Substitution Test (DSST) and Stroop Test (ST). Analysis of covariance was conducted to compare differences in group means of intra‐network FC of FEN, FPN and DMN and executive function tests performance at trial completion, with baseline outcome scores as covariate. Pearson correlations were computed to determine whether changes in executive performance between baseline and trial completion were related to changes in FC in the RT group.ResultAt trial completion, there were no significant between‐group differences in intra‐network FC of FEN, FPN and DMN. RT significantly improved ST performance (estimated mean change[95%CI]: ‐11.322[‐22.366, ‐0.277], p = 0.045) compared with BAT; there were no significant between‐group differences in TMT and DSST. Within RT group, improved ST performance was significantly correlated with increased intra‐network FC of FEN (r = ‐0.697, p = 0.006).ConclusionRT‐induced improvement in ST performance was associated with increased intra‐network FC of FEN. More research is needed to determine whether exercise training has an effect on the neural correlates of cognitive reserve.
A scalable solution for precisely measuring low abundant neurobiomarkers from micro‐sampling
Authors: Fan Tsz Wing , Kim WonHee , Thomas Corinne , Jiang Wenjing , Tan Jeremy , Xuan Feng 
Published: January 2025

AbstractBackgroundCutting‐edge ultrasensitive immunoassay platforms have unveiled the potential of blood‐based biomarkers, offering detection at low fg/mL levels for early neurodegenerative disorder prognosis, screening, and therapeutic monitoring. Current immunoassays, such as single molecule array (SIMOA) and mesoscale multi‐array (MSD), face limited adoption due to their reliance on specialized equipment. Additionally, they require immobilization of probe reagents and a washing process, demanding tens of thousands of proteins to achieve the Limit of Detection (LOD), leading to the requirement of high sample volume and high affinity antibodies for fg/mL sensitivity. Addressing the escalating need for non‐invasive, small‐volume sample collection, along with an accessible platform for frequent longitudinal monitoring and population‐scale screening, a solution with these features is imperative.MethodIntroducing Successive Proximity Extension Amplification Reactions (SPEAR), which employs a unique two‐factor authentication mechanism that eliminates the background in conventional homogeneous assay, detects down to single‐digit copies of proteins. SPEAR utilizes a simple three‐step wash‐free workflow adaptable to any liquid handler and readable on ubiquitous PCR machines. To showcase its utility in detecting neurobiomarkers at low concentrations in blood, we demonstrate NFL assay using just 1‐mircorliter diluted plasma sample to reach low fg/mL sensitivity with excellent precision. Comprehensive testing included spike‐in recovery, dilution linearity and specificity against neurofilaments (Nf‐M, Nf‐H, peripherin, and α‐internexin), precision and accuracy.ResultSPEAR NFL assay exhibited remarkable LOD and Lower Limit of Quantification (LLOQ) from two commercial readily available NFL antibody pairs. The LOD was measured at 51 and 90 fg/mL using 1 µL of 1:4 diluted plasma. Robust precision was indicated by low intraplate and lot‐to‐lot %CV (6% and 7%, respectively), and high concordance against Simoa® NF‐light™ V2 Advantage Kit and MSD Splex kit using 36 K2EDTA plasma samples.ConclusionSPEAR has demonstrated validated sensitivity against existing NFL detection platforms. Its standout features, including minimal sample volume requirement and compatibility with standard PCR machines, coupled with advances in portable PCR machines and remote collection devices, position SPEAR as a robust and accessible tool for neurodisease diagnostic and research.
Clinical Profile of Dementia in Bed‐Bound or Home‐Bound Elderly Individuals from Low‐Income Communities in Southeast Brazil
Authors: Real Ana Paula Bernardes , de Moraes Flavia Lanna , de Moraes Edgar Nunes , Machado Carla Jorge 
Published: January 2025

AbstractBackgroundAging is linked to an increased risk of dementia, a significant cause of functional decline in the elderly, necessitating long‐term care.MethodsDementia prevalence rates by age categories were obtained for bed‐bound or home‐bound elderly individuals from a public health system’s home care service in communities of Belo Horizonte/MG, to assess the independent effect of age. Analyses were conducted using Stata/SE for Macintosh 12.0 and included descriptive measures and adjusted prevalence ratios using Poisson Regression analysis with robust standard deviations. Results were considered significant at p<0.05.ResultsA total of 1,092 dementia patients were evaluated, aged 70‐79 (28.6%), 80‐84 (19.9%), and 85‐90 (18.9%). Over half had less than 4 years of education (53.5%). The primary etiologies of dementia were Alzheimer’s disease alone (28%), isolated vascular dementia (13.8%), and mixed dementia (10.9%). The prevalence of other etiologies like frontotemporal dementia, Lewy body dementia, and dementia associated with Parkinson’s disease were low. Dementia prevalence by age group was 39.4% (60‐69 years); 55.6% (70‐79); 58.3% (80‐84); 69.6% (85‐89); 72.2% (90‐94) and 79.1% (95 years or older). Compared to the age group 60‐69 years, the PR was 1.4 for 70‐79; 1.5 for 80‐84; 1.8 for 85‐89; 1.9 for 90‐94; and 2.1 for 95 years or older (p<0.005 for all PRs). The average Charlson Comorbidity Index (CCI) was 5.1 (standard deviation 1.8), and the proportion of frail elderly was 95%. Poisson regression revealed that dementia prevalence was not affected by CCI or education level, but there was an independent effect of age group and frailty. Male gender was negatively and independently associated with dementia (PR = 0.80; p<0.001), while frailty was positively and independently associated with dementia (PR = 14.9; p<0.001).ConclusionThe primary cause of dementia was Alzheimer’s disease, following the pattern reported in the literature. Age was independently associated with dementia. Dementia was strongly linked to the severity of the clinical‐functional frailty presented by the elderly.