bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effects of sleep duration and physical activity on cognitive performance are influenced by β‐amyloid and brain volume but not tau burden among cognitively unimpaired older adults
Authors: Aslanyan Vahan , Ortega Nancy E , Fenton Laura E. , Harrison Theresa M. , Raman Rema , Mack Wendy J , Pa Judy 
Published: December 2023

AbstractBackgroundSleep and physical activity have gained traction as modifiable risk factors for Alzheimer’s disease (AD). Sleep duration is linked to amyloid‐β (Aβ) clearance while physical activity is associated with brain volume maintenance. We investigate associations between sleep duration and physical activity and cognition by testing if sleep duration—cognition and physical activity—cognition are explained by Aβ deposition and brain volume, respectively. Additionally, we explore the mediating role of tau burden in these relationships.MethodThis cross‐sectional study obtained data from participants in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study, a randomized clinical trial. Cognitively unimpaired participants underwent Aβ and tau PET and brain MRI prior to randomization. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Self‐reported nightly sleep duration and weekly physical activity were the primary predictors. Regional Aβ and tau pathologies and volumes were the proposed variables influencing sleep duration—cognition or physical activity—cognition relationships.ResultAβ PET data were obtained from 4322 participants (1208 with MRI, 59% female, 29% amyloid positive). Sleep duration was associated with an Aβ composite burden (β = ‐0.005,CI:(‐0.01,‐0.001)) and Aβ burden in the anterior cingulate (ACC) (β = ‐0.012,CI:(‐0.017,‐0.006)) and medial orbitofrontal cortices (MOC) (β = ‐0.009,CI:(‐0.014,‐0.005)) but not with brain structure. Composite (β = ‐1.54,CI:(‐1.93,‐1.15)), ACC (β = ‐1.22,CI:(‐1.54,‐0.90)) and MOC (β = ‐1.44,CI:(‐1.86,‐1.02)) Aβ burden were also associated with PACC. Sleep duration—PACC association was explained by Aβ burden in path analyses (Figure 1). Physical activity was not associated with Aβ but was associated with hippocampal (β = 10.57,CI: (1.06,20.08)), parahippocampal (β = 9.3,CI:(1.69,16.91)), entorhinal (β = 14.68,CI:(1.75,27.61), and fusiform gyral (β = 38.38,CI:(5.57, 71.18)) volumes, which were also positively associated with PACC (p<0.02 for hippocampus, entorhinal cortex, and fusiform gyrus). Physical activity—cognition relationship was explained by regional volumes (Figure 2). Tau was not related to sleep duration or physical activity, and it did not moderate relationships between cognition and sleep duration or physical activity.ConclusionSleep duration and physical activity are associated with cognition through independent paths of brain Aβ and brain volume, respectively, but not tau burden. Dementia risk reduction approaches that emphasize the adequate sleep duration and a physically active lifestyle may benefit those with risk for AD.
Total and posterior cerebral blood flow is associated with white matter hyperintensity volume and Alzheimer’s‐like patterns of brain atrophy in older adults
Authors: Pyne Jeffrey , Morales Clarissa , Alshikho Mohamad J , Lao Patrick J. , Turney Indira C , Gutierrez Jose , Manly Jennifer J. , Mayeux Richard , Brickman Adam M. 
Published: December 2023

AbstractBackgroundSmall vessel cerebrovascular disease, often visualized as white matter hyperintensities (WMH) on T2‐weighted MRI scans, contributes to risk, progression, and, possibly, pathogenesis of Alzheimer’s disease (AD). When considered in the context of previous neuroimaging biomarker work in AD, WMH appear to colocalize with other markers of disease risk and progression, including metabolic changes, atrophy, and tau pathology, in areas perfused by the posterior circulation. In the current study, we used a novel MR‐based method, termed phase contrast, to quantitate total cerebral blood flow in anterior and posterior circulations and test its relationship with WMH volume and an AD‐like pattern of brain atrophy in older, community‐dwelling adults.MethodTwo hundred forty‐five older adult participants (77±5.6 mean±SD age, 66% women, 42% Latinx, 30% Black, and 28% White individuals) in the Washington Heights Inwood Columbia Aging Project (WHICAP) received T1‐weighted, T2‐weighted (FLAIR), and phase contrast MR imaging. 2D phase contrast imaging can be used to quantify absolute blood flow rates with cross‐sectional velocity‐encoding of major vasculature leading into the brain. Blood flow rates in the anterior circulation (carotid arteries) and posterior circulation (vertebral arteries) were derived with Medis QFlow 4.0. WMH volume and cortical thickness in AD‐signature regions were derived with in‐house software and FreeSurfer v6.0, respectively. Separate general linear models tested the association of total, anterior, and posterior blood flow rates with WMH volumes and AD‐signature cortical thickness.ResultLower total cerebral blood flow was associated with increased total WMH volume (β = ‐0.14, p<0.05, 95%CI [‐1.37E‐2, ‐7.32E‐4]), an effect that was stronger for posterior flow (β_posterior = ‐0.17, 95%CI [‐3.7E‐2, 2.5E3], β_anterior = ‐0.11, 95%CI [‐1.9E‐2, 5.4E3]). Lower posterior blood flow specifically was associated with lower AD‐signature cortical thickness, but only in older participants (age interaction term: β = ‐3.14, p<0.01, 95%CI [‐2.0E‐4, ‐3.5E‐5]).ConclusionLower total cerebral blood flow, particularly in the posterior circulation, is associated with increased WMH volume and decreased cortical thickness, two neuroimaging markers that are implicated in risk and progression of AD. Future work that examines whether or how diminished total cerebral blood flow accounts for the colocalization of AD biomarkers across modalities will provide insight into the vascular contributions to AD.
Dementia Risk Factors Predict Individual Differences in Cognitive Function
Authors: Hennessee Joseph P. , Katen Carson D. , Monier Sarah A. , Park Denise C. 
Published: December 2023

AbstractBackgroundTwelve modifiable risk factors have been estimated to account for 40% of dementia incidence worldwide (Livingston et al., 2020). Growing understanding of these risk factors presents the possibility that dementia risk can be partially mitigated via non‐pharmacological means, such as changes in lifestyle (e.g., alcohol consumption, social activity). We sought to provide the first systematic investigation of whether this set of risk factors also contributes to individual differences in cognitive function in a cognitively‐normal sample, and which risk factors provide the strongest contribution.MethodWe investigated cross‐sectionally the association between eight of these risk factors and cognition in 246 cognitively‐normal adults, aged 50‐90 from the Dallas Lifespan Brain Study. Risk factors included alcohol use (drinks per week), body mass index (BMI), cigarettes smoked per day, depressive symptoms (CESD scale), years of education, exercise frequency (20+ min sessions), pulse pressure, and frequency of social activity. A general measure of cognition, fluid ability, was used as the outcome variable and it was an average of six commonly used assessments of processing speed, working memory, and reasoning.ResultIn a multiple regression controlled for age and sex, 15.6% of fluid ability variance was accounted for by years of education (R
2 = .040, p = .002), frequency of social activity (R
2 = .034, p = .004), BMI (R
2 = .030, p = .008), cigarettes smoked per day (R
2 = .020, p = .032), and depressive symptoms (R
2 = .017, p = .047), as well as non‐significant contributions from alcohol use, exercise frequency, and pulse pressure. Further analysis examining cortical amyloid‐beta burden as a predictor and moderating effects of age will be discussed.ConclusionThe findings illustrate that levels of these modifiable risk factors affect cognition, even in a large sample of adults unselected for AD risk. We report differences in magnitude of effects for adults who showed cognitive decline over 10 years compared to those who were stable.References: Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., … & Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), 413‐446.
Effects of clutter on reaching in posterior cortical atrophy and typical Alzheimer’s Disease
Authors: Bancroft Matthew J , Hayes Oliver S , Ocal Dilek , Brotherhood Emilie V , Hoe Juanita , Kaski Diego , McIntosh Robert D , Crutch Sebastian J , Day Brian L , Yong Keir X X 
Published: December 2023

AbstractBackgroundPosterior cortical atrophy (PCA) is a neurodegenerative syndrome most commonly caused by Alzheimer’s disease (AD) and is often considered the most common atypical AD presentation. PCA is characterised by predominant visual rather than memory loss and occipito‐parietal/occipito‐temporal atrophy (‘visual‐spatial AD’). Characteristic visual‐spatial deficits in PCA include difficulty perceiving objects among visual clutter, consistent with excessive visual crowding. However, there is conflicting guidance and limited empirical evidence regarding management of such perceptual deficits. Here we investigate effects of clutter when reaching to objects with the upper limb.MethodPatient (total n = 38; PCA n = 21; typical AD [tAD] n = 17) and control (n = 18) participants repeatedly reached to a visual target presented on a computer screen (white square on a grey background; n = 100 trials per participant). The target appeared in one of five positions along the medio‐lateral axis (Fig 1) and was presented under different flanker (unflanked, flanked [shape/coloured distractors]), spacing (condensed, spaced; Fig 2) and flicker conditions (static, flicker). Outcome measures were reach completion time (time from target presentation to completion of the reach) and spatial accuracy (medio‐lateral distance between target and finger position at reach completion), determined using motion capture.ResultReach accuracy was comparable between groups and across conditions. However, reach completion was slower in both patient groups (group: p<0.001) and PCA were particularly affected by target‐flanker spacing (group‐by‐spacing: p<0.001). When reaching to unflanked targets, completion times were quickest in control (estimated mean [95%CI]: 1.2s [1.0,1.4]), slowest in PCA (2.3s [1.9,2.6]) and intermediate in tAD groups (1.5s [1.3,1.8]; Fig.2). Slower reaching to flanked targets was particularly apparent in PCA relative to tAD and control groups, especially with condensed flankers (Fig.2). Slower reaching to flanked targets was somewhat mitigated by increasing target‐flanker spacing; exaggerated spacing effects in the PCA group are consistent with excessive visual crowding (estimated decrease in completion time spaced vs condensed: PCA: ‐14.4% [‐11.1, ‐17.7]; tAD: ‐5.2% [‐2.5, ‐7.9]; Control: ‐4.8% [‐2.9, ‐6.6]).ConclusionFindings suggest visual crowding – normally restricted to healthy peripheral vision – impairs reaching to targets presented in central vision in PCA. Findings may inform symptom and environment management strategies for people with visual loss arising from neurodegenerative disease.
Vision and Hearing Difficulty as a Modifier of the Effects of Cognitive Training Over 5 and 10 Years in Older Adults
Authors: Huang Alison R , Rebok George , Deal Jennifer A 
Published: December 2023

AbstractBackgroundCognitive training interventions are delivered visually and/or aurally. Whether sensory loss modifies its effect in older adults is unknown. We assessed differences in the effect of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study, a randomized cognitive training intervention trial, by self‐reported vision and hearing difficulty.MethodsParticipants (65 years and older, cognitively/functionally healthy) were randomized to cognitive training in memory, reasoning, or speed of processing or a no‐contact control. Composite scores were created using multiple cognitive assessments in memory, reasoning, and speed of processing. Self‐reported near vision difficulty was defined as reading ordinary print in the newspaper (no difficulty/a little or some difficulty), and hearing loss was self‐reported (yes/no). Differences in the 10‐year effect of cognitive training on change in trained cognitive ability were assessed using linear mixed effect models adjusted for demographic and study design characteristics.ResultsAmong 2,788 participants, 22% reported vision difficulty and 43% reported hearing loss. Participants with sensory loss benefited from all cognitive training interventions (Figure 1); however, the magnitude of benefit of reasoning training was smaller among participants with vs. without vision difficulty (10‐year difference in reasoning ability [intervention vs. control]: vision difficulty: ‐0.25, 95% CI: [‐0.88, 0.39], no vison difficulty: 0.58, 95% CI: [0.28, 0.89]). Magnitude of benefit of memory training was greater for participants with vs. without hearing loss (10‐year difference in memory ability [intervention vs. control]: hearing difficulty: 0.17, 95% CI: [‐0.37, 0.72], no hearing difficulty: ‐0.20, 95% CI: [‐0.65,0.24]). Beneficial effect of speed of processing training was similar by sensory status.ConclusionParticipants with vision difficulty did not benefit as much from reasoning training, likely because training required more visually complex exercises (e.g., deciphering patterns across similar symbols). Memory training was more efficacious for participants with hearing loss, perhaps because training provided compensation strategies for overcoming cognitive load (increased effort for processing degraded auditory signals). Cognitive training interventions should consider sensory function in design and administration. Individuals with sensory loss have increased risk for cognitive decline and should not be excluded from cognitive training interventions as magnitude of benefit may be greater for these individuals.
Diversity in Biomarkers: Challenging Expectations of Serum Tau Positivity
Authors: Schirtzer Emily A , West Jennifer , Torres Sandra , Cassidy Stephanie , Baez‐Torres Sheila 
Published: December 2023

AbstractBackgroundAlzheimer’s disease has been thought to affect minority populations at higher rates than the Caucasian population. While recent advancements in biomarkers have been promising, we expected to see a similar correlation with biomarker positivity rates. However, our data has revealed that serum TAU biomarker testing in older healthy populations reveals a positivity rate much higher in Caucasian vs. Black participants as well as in Non‐Hispanic vs. Hispanic participants.MethodData from 1,223 cognitively unimpaired trial participant subjects was analyzed. Of those participants 120 were Black and 1,066 were Caucasian. Data from 36 participants of other minority races and one participant who chose not to reveal race were also collected but for the purpose of this presentation are not being addressed at this time. Data on ethnicity was also collected, revealing 262 Hispanic and 961 Non‐Hispanic participants. Again, one participant chose not to reveal ethnicity.ResultPercentages of positivity were collected and analyzed. While we expected to see rates of positivity two times higher for Black participants than Caucasian participants, what was actually noted was 10.5% positivity for Caucasian and 6.7% positivity for Black or African Americans. Similarly, we expected to see positivity among Hispanic participants at 1.5 times greater than Non‐Hispanic participants. What instead was noted was very similar rates of positivity with Non‐Hispanic at 10% positivity and Hispanic at 11.1% positivity.ConclusionIn analyzing positivity rates of serum TAU among certain race and ethnicity groups, we expected to see evidence of pathology similar to rates of reported actually diagnosed diseases. However, the data obtained is trending differently. While the initial data was from a relatively small sample population, the collection of additional data will help further analyze if this trend will continue to reveal rates of positivity contradictory to what is expected.
Evaluation of the cerebral vascular morphostructural in a model for Alzheimer’s disease after the intervention with physical exercise.
Authors: Soto‐Rojas Luis Oskar , Díaz‐Cintra Sofia , Jesús Andrade José , Orta‐Salazar Erika 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disease in the world. It is characterized by impaired memory, thinking, orientation, and learning, thus affecting the quality of life of people whosuffer from it. The two pathognomonic hallmarks are the neuritic plaques and neurofibrillary tangles, however, the vascular system is also affected, aggravating the symptoms of the disease, being a possible hypothesis of the development of the disease. One of the most widely used animal models to study disease mechanisms is the 3xTg‐AD triple transgenic mouse that contains three mutations associated with familial AD (PS1M146V, APPSWE, and tauP301L). Among the non‐pharmacological treatments is physical exercise, which is a variety of planned, repetitive, and dosed physical activity, proving to be safe as part of the adjuvant treatment of the disease, however, its effect on the vascular system is unknown.MethodA total of 40 ten‐month‐old female mice, 3xTg‐AD (n = 20) and NonTg (n = 20), equally divided into exercise and sedentary groups, were used. An intervention of voluntary physical exercise was carried out for 3 months with a frequency of 5 times a week. Subsequently, memory and learning were evaluated using the Barnes maze test. The vascular morphostructure by anatomical analysis through histological assays using markers for vascular basement membrane (anti‐Collagen IV) and pericytes (anti‐PDGFR‐β), in addition to amyloid deposits. No improvement in cognitive ability was observed, however, exercise promoted the recovery of the vascular system, as well as the reduction of amyloid deposits.ResultNo improvement in cognitive ability was observed, however, exercise promoted the recovery of the vascular system, as well as the reduction of amyloid deposits.ConclusionThe intervention with voluntary physical exercise promotes stability of the vascular system as well as the reduction of amyloid deposits in the symptomatic stages of the disease.
Designing Attitudinal Environments to Address Stigma: Virtual Film Screenings and Panel Discussions on Dementia in a Health Promotion Program
Authors: Park Melissa , Lee Keven , Yang Seiyan , Francioni Arnaud , Sénéchal Christian , Belchior Patricia , Bourdais Marie Christine Le , Valente Thomas W. 
Published: December 2023

AbstractBackgroundIntersectoral partnerships are critical for effective and sustainable health promotion programs. Yet stigma and misperception continue to interfere with public engagement in dementia prevention programs, outreach, and willingness to access to dementia and‐or mental health related services for persons living with Alzheimer’s and‐or related disorders and personal carers. The aim of our Public Health Agency of Canada Dementia Community Investment project, What Connects Us∼Ce Qui Nous Lie (2020‐2023), was to collaboratively cultivate sociocultural environments worth living in using shared activities and events to address stigma at the intersection of dementia, aging and mental health. In this paper, we present initial results on the effectiveness of using on‐line, community screenings of short films featuring stories about living with dementia, followed by curated panel discussions with the film directors, arts/culture partners, policy makers and other stakeholders.MethodWe employed a mixed methods ethnographic approach to describe and measure the impact of six film screenings with pre/post‐film and then later post‐discussion measures of semantic sentiment. All discussions were simultaneously interpreted, and based on open‐ended qualitative questions that had been developed with panelists prior to the screening. The qualitative questions asked for one word/phrase responses to generate word clouds in French and English. Three researchers then assessed the words/phrases until agreement on positive or negative value was reached. French words were back‐translated into English prior to analysis using suzy‐net, a natural language processor, to confirm positive/negative valence and to measure changes within each film screening and across all film screenings.ResultThere was a significant change in sentiment from negative (e.g., frustration, lies, loss, confusion) to positive sentiment (e.g., humanity, empathy, compassion, understanding) across all waves within and across the six screenings, with the most change occurring post‐discussion. In addition, partners and project‐related team members were removed from the analysis to test for partner participation confounding with the overall shift in valence remaining the same.ConclusionFilms about living with dementia, and curated questions developed in collaboration with panelists and directors of 1st person experiences can positively impact changes in sentiment about dementia.
Structural and functional Analysis of novel 3‐Nitrotyrosine Aβ‐specific Antibodies
Authors: Kottwitz Anna Katharina , Piechotta Anke , Parthier Christoph , Linnert Miriam , Roßner Steffen , Schilling Stephan , Rahfeld Jens‐Ulrich 
Published: December 2023

AbstractBackgroundPosttranslational modified (PTM) amyloid peptides are increasingly within the spotlight of Alzheimer’s drug research. Some of these modifications, such as the formation of pyroglutamate or isoaspartate, are associated with the deposition and increased toxicity of amyloid peptides. The role of nitration at Tyr10 of Aβ and its abundance in AD brain is less well understood. How 3NY10‐Aβ is formed is controversial, as well as the influence on aggregation behaviour. Hence, we here aimed at generation and characterization of monoclonal antibodies specific for 3NY10‐Aβ as research tool and potential therapeutic molecules.MethodMonoclonal antibodies were developed by immunizing mice with 3NY10‐Aβ(6‐14) and derivation of corresponding hybridoma cell lines. Characterisation of the antibodies was achieved by a variety of biochemical and kinetic analyses: isothermal titration calorimetry (ITC), dot blot analysis and ThioflavinT aggregation studies. X‐ray crystallography was used for structure determination. We used immunohistochemical (IHC) staining of brain tissue from 5xFAD mice and enzyme linked immune sorbent assay (ELISA) to assess the formation of 3NY10‐Aβ in transgenic mice.ResultTwo highly affine 3NY10‐Aβ antibodies 4C3 and 3B3 have been generated, both binding 3NY10‐Aβ(1‐16) in the nanomolar range (KD4C3 = 11 nM, KD3B3 = 88,5 nM) as determined by ITC. The specificity of the antibodies was confirmed by dot blot analysis, using several post‐translationally modified Aβ‐peptides. Aggregation studies of 3NY10‐Aβ(1‐40/42) peptides in presence of 3B3 or 4C3 showed an influence of fibril formation, as could be verified by means of transmission electron microscopy. Co‐crystallisation of 4C3 Fab‐fragment and 3NY10‐Aβ(1‐16) at a resolution of 2.5 Å revealed a binding of 3NY10. To investigate the role of 3NY10‐Aβ in AD, IHC‐staining of brain from mice with AD‐like pathology (5xFAD mice) was performed. The data support presence of 3NY10‐Aβ within amyloid deposits, although staining appeared weak. Likewise, a Sandwich‐ELISA of homogenized murine brain tissue displayed no significant proportion of 3NY10‐modified Aβ in relation to the total Aβ(1‐40/42).ConclusionIt has been demonstrated that the unique monoclonal 3NY10‐Aβ specific antibodies 4C3 and 3B3 are a suitable tool for investigating the role of 3NY10‐Aβ in AD. Future research aims to quantify the level of 3NY10‐Aβ in human brain tissue with AD‐pathology.