bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Investigation into The Role of Lifestyle Factors in SuperAgers
Authors: Watson Philippa , Koychev Ivan , Gallacher John , Bauermeister Sarah 
Published: January 2025

AbstractBackgroundIt is widely acknowledged that cognitive abilities tend to decline with age; however, there exists considerable intra‐individual variability in the rate of decline. While many individuals report varying degrees of cognitive decline, a small subset known as “SuperAgers” exhibits cognitive abilities comparable to those several decades younger. Our understanding of which factors enable SuperAgers to maintain their superior cognitive abilities is inconclusive. It is hypothesized, however, that the factors safeguarding against cognitive decline may also play a role in maintaining exceptional cognitive abilities.MethodThis study leverages data collected during Phase 5 (1997‐1999) and Phase 12 (2015‐2016) of the Whitehall II cohort, a longitudinal study focusing on British civil servants. SuperAgers were defined as those over 65 years old at Phase 12 who scored in the top tercile for verbal memory performance in Phase 12 and who performed above the mean for verbal memory at Phase 5. Structural equation modelling will be employed to conduct a multivariate statistical analysis investigating the association between engagement in various lifestyle factors (e.g., mental health, physical activity, social engagement, and biomedical factors) in SuperAgers and cognitively normal agers (CN’s).ResultThe study comprised 1,963 participants (511 females), with 812 meeting the criteria for SuperAgers and 1,156 for CN’s. SuperAgers exhibited lower levels of hypertension (t = 5.13, p < .001), medications (t = 2.86, p = .002), BMI (t = 1.79, p = .04), and higher engagement in high social activities (t = 3.44, p < .001), low social activities (t = 2.90, p = .002), and vigorous physical activities (t = ‐2.00, p = .02). No significant differences were observed between SuperAgers and CN’s regarding smoker status, alcohol consumption, sleep duration, mental health, and cardiovascular diseases (p > .05). Additional analyses are ongoing and will be completed by the conference date.ConclusionThe findings from this study will provide valuable insights into the contribution and significance of various modifiable lifestyle factors in preserving cognitive function during older age.
Lung function and risk of incident dementia: A prospective cohort study of 431,834 individuals
Authors: Yang Liu , Yu Jin‐Tai 
Published: January 2025

AbstractBackgroundWhether lung function prospectively affects cognitive brain health independent of their overlapping factors remains largely unknown. This study aimed to investigate the longitudinal association between decreased lung function and cognitive brain health and to explore underlying biological and brain structural mechanisms.MethodThis population‐based cohort included 43,1834 non‐demented participants with spirometry from the UK Biobank. Cox proportional hazard models were fitted to estimate the risk of incident dementia for individuals with low lung function. Mediation models were regressed to explore the underlying mechanisms driven by inflammatory markers, oxygen‐carrying indices, metabolites, and brain structures.ResultDuring a follow‐up of 3,736,181 person‐years (mean follow‐up 8.65 years), 5,622 participants (1.30%) developed all‐cause dementia, which consisted of 2,511 Alzheimer’s dementia (AD) and 1,308 Vascular Dementia (VD) cases. Per unit decrease in lung function measure was each associated with increased risk for all‐cause dementia (forced expiratory volume in 1 s [liter]: hazard ratio [HR, 95%CI], 1.24 [1.14‐1.34], P = 1.10 × 10−07; forced vital capacity [liter]: 1.16 [1.08‐1.24], P = 2.04 × 10−05; peak expiratory flow [liter/min]: 1.0013 [1.0010‐1.0017], P = 2.73 × 10−13). Low lung function generated similar hazard estimates for AD and VD risks. As underlying biological mechanisms, systematic inflammatory markers, oxygen‐carrying indices, and specific metabolites mediated the effects of lung function on dementia risks. Besides, brain grey and white matter patterns mostly affected in dementia were substantially changed with lung function.ConclusionLife‐course risk for incident dementia was modulated by individual lung function. Maintaining optimal lung function is useful for healthy aging and dementia prevention.
Resting‐state brain activity and association with baseline physical activity
Authors: Koromila Georgia , Faraza Sofia , Dyrba Martin , Wolf Dominik , Fischer Florian U , Knaepen Kristel , Kollmann Bianca , Binder Harald , Mierau Andreas , Riedel David , Fellgiebel Andreas , Tüscher Oliver , Teipel Stefan 
Published: January 2025

AbstractBackgroundNormal aging is associated with alterations of functional connectivity (FC) in brain neuronal networks. Altered network connectivity may be associated with accelerated cognitive decline. Physical activity is considered a beneficial lifestyle factor for maintaining cognitive health. Higher intensities of physical activity may induce structural and functional changes in the brain, particularly in regions involved in cognitive functions, such as memory, attention and executive functions. However, the underlying neural mechanisms are not widely investigated. Our aim was to examine the association between resting‐state FC of brain networks and baseline physical activity in healthy older adults.MethodWe analyzed baseline resting‐state fMRI and baseline physical activity data of 149 healthy older adults (mean age: 68 years) from the AgeGain study. Physical activity was measured by using actigraphs worn for 7 days. Different intensities were measured, such as light, mean and moderate‐to‐vigorous activity (min/d). We used Independent Component Analysis (ICA) and seed‐based approaches to examine brain network activity in the Default Mode Network (DMN), Salience Network (SAL), Central Executive Network (CEN), Visual Network (VN) for cognitive effects and Sensorimotor Network (SMN) for physical effects.ResultWe observed statistically significant associations between functional activation within SMN and light physical activity and spatially restricted effects for DMN and moderate‐to‐vigorous physical activity (p <.01 uncorrected). In addition, we observed an overlap on frontal activation across DMN, SMN and SAL. Results of the seed‐based analysis will be presented at the conference.ConclusionLight to higher intensities of physical activity showed an association with higher functional activation of networks previously associated with cognitive decline and physical activity. This agrees with the notion that physical activity may be a protective factor against cognitive decline. Further research is needed to test the replicability of these results.
Effect of combination treatment with escitalopram and risperidone in punding behaviour among patients with dementia‐ a retrospective study
Authors: Tripathi Shailendra Mohan , Shahi Mohit Kumar , Chutia Porimita 
Published: January 2025

AbstractIntroductionPunding is a unique stereotypical, repetitive, non‐goal‐directed behavior characterized by an intense fascination with daily objects. This behavior although commonly seen in dementia patients is relatively less studied. In this study, we aimed to assess the effectiveness of combination treatment of escitalopram and risperidone treatment in the punding behavior of dementia patients.MethodologyA retrospective study of dementia patients with punding behavior treated inpatient with a combination treatment of escitalopram and risperidone from January 2023 to October 2023. A semi‐structured proforma was used to collect the demographic details, illness information, and outcomes based on standardized rating scales from the records of a tertiary care center in India. The data were analyzed using paired t‐test and McNemar test.ResultsA total of 29 patients, 17 females and 12 males with a mean age of 74.14 ± 7.18 years were included. A significant decline was found in the Neuropsychiatric Inventory (NPI) motor behavior subscale score and caregiver distress related to motor behavior from Day 0 to Day 7 (p‐value of 0.0002, p = 0.001) on the combination treatment. However, the total NPI Severity Score and total QUIP‐RP Score (for repetitive behavior) exhibited a reduction in scores from Day 0 to Day 7 but the p‐value was non‐significant.ConclusionThe study adds valuable insights into the management of punding behavior and its associated distress providing a basis for further research on the neurobiological underpinnings of this distinctive symptom in dementia.
Cognitive Screening of Community‐Dwelling Older Adults in Shanghai Using a Game‐based Mobile Screening Tool: A Cross‐Sectional Study
Authors: Wu Jingnan , Zhou Zhixing , Xia Huanhuan , Chen Nan , Li Yatian 
Published: January 2025

AbstractBackgroundGame‐based Cognitive Assessment – 3‐minute Version (G3) is a self‐administrated mobile screening tool for detecting early cognitive impairments among Chinses community‐dwelling older adults. Released as a WeChat and Alipay mini‐programs, G3 offers a convenient and cost‐free means for individuals to evaluate their cognitive functions online. This study aimed to investigate the cognitive performance of older adults in the Shanghai community with G3. Additionally, a comparison was made between the cognitive performance of older adults who participated in the screening offline and those who proactively participated online.MethodBetween June and October 2023, an offline cognitive screening with G3 tests was performed in Xiaodongmen subdistrict of Shanghai. And G3 results of 3344 participants aged 55‐89 years old were enrolled for restrictive analysis. Simultaneously, G3 online assessment records between January and December 2022 completed by 64535 individuals aged 55‐89 years old from various regions of China, were reviewed and compared to the offline screening results.ResultAmong older adults aged 55 to 89 in Xiaodongmen communities, the average G3 score (mean ± stand deviation) was 56.82±12.47. Furthermore, the mean G3 score for males and females was 57.23±12.29 (n = 1569) and 56.46±12.61(n = 1775), respectively, both of which exhibited a trend of cognitive decline with increasing age (Figure 1). Moreover, older adults with a high school education or higher demonstrated significantly better cognitive performance compared to those without (p<0.05, Figure 2). When comparing the online self‐administrated G3 results of age‐matched older adults, both cohorts displayed a similar trend of cognitive decline with increasing age. However, the average G3 score obtained from Xiaodongmen subdistrict was statistically lower than that of the online assessments (p<0.05, Figure 3).ConclusionThis study characterized the cognitive function among older adults in Shanghai and enhanced the feasibility of G3 tool for large‐scale cognitive screening in Chinese communities. Nonetheless, due to the notable disparity between online and offline screening results, further investigations are warranted to explore the underlying mechanisms.
AAV9‐SORL1 gene therapy for Alzheimer’s disease
Authors: Andersen Olav M. , Qureshi Yasir H. , Jensen Anne Mette Gissel , Williams Andrew , Young Jessica E. , Roy Mimi , Klein Joel , Armstrong Rob , Merchant Kalpana M. 
Published: January 2025

AbstractBackgroundConvergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer’s disease (AD). SORL1 encodes the retromer‐associated receptor SORLA that plays an essential role in recycling of AD‐associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD. Moreover, both SORLA and retromer protein levels are reduced in the most vulnerable regions of AD brains. Thus, restoration of SORLA levels and function via viral transduction is an attractive therapeutic strategy. Unfortunately, the full‐length SORL1 is too large to be packaged into a viral capsid for gene therapy.MethodWe identified and tested endosomal recycling effects of a truncated SORL1 mini‐gene construct after transient transfections in HEK293 cells. We developed a gene therapy lead by packaging SORL1 mini‐gene into AAV9. This lead was tested for expression and activity in neurons differentiated from human induced pluripotent cells (hiPSC) as well as in vivo after brain infusions in wild‐type mice and SORL1 haploinsufficient Göttingen minipigs by biochemistry and immunohistochemistry.ResultExpression of the SORL1 mini‐gene in HEK293 cells increased endosomal recycling of full‐length SORLA as shown by elevated cell surface expression and shedding of the SORLA mini receptor. In hiPSC neurons, AAV9‐SORL1 treatment resulted in strong endosomal expression of the SORLA mini‐receptor that co‐localized with components of the retromer complex in endosomes. In vivo, we observed dose‐dependent transduction and expression of SORLA mini‐receptor in neurons, which localized to endosome‐like punctate structures. Evaluation of functional effects is underway.ConclusionWe conclude that the AAV9‐SORL1 mini‐gene expresses SORLA mini‐receptor in neurons which resides in intracellular vesicular endosomal structures together with the retromer complex and has the capacity to boost the endosomal recycling pathway. Thus, the SORL1 mini‐gene is a promising candidate for gene‐therapy for AD patients.
The influence of the adherence on intervention effect: J‐MINT study
Authors: Uchida Kazuaki , Sugimoto Taiki , Matsumoto Nanae , Fujita Kosuke , Yokoyama Yoko , Kuroda Yujiro , Sakurai Takashi , Arai Hidenori 
Published: January 2025

AbstractBackgroundThis study aimed to examine the influence of adherence on intervention effect in the Japan‐multimodal intervention trial for the prevention of dementia (J‐MINT).MethodJ‐MINT was an 18‐month randomized controlled trial, and participants aged 65‐85 years with mild cognitive deficits were randomized into multidomain intervention (physical exercise, nutritional counseling, cognitive training, and vascular risk factor management) and control groups. This study included the participants in J‐MINT who had undergone the intervention program and follow‐up evaluation at least once. Adherence in each intervention component was classified as adherent (1 point) or non‐adherent (0 point), and the total score was calculated (score range: 0‐4 points). Adherent was defined as follows: the adherence rate to group‐based physical exercise ≥ 70%, the number of nutritional counseling ≥ 14 times, the number of days of cognitive training ≥ 156 days, and those who have blood pressure, glucose levels, and cholesterol within the target range. Three groups were created based on the total score: adherent group (4 points), partially adherent group (2‐3 points), and non‐adherent group (0‐1 points). The outcome was the changes in composite score calculated by eight neuropsychological tests from baseline to 18 months, including tests of global cognitive function, memory, attention, and executive function/processing speed. Mixed models for repeated measures were used to calculate mean differences (MD) of outcome between each adherence and control group.ResultOut of 531 participants enrolled in J‐MINT, 421 participants (mean age: 73.8 years, 52% female) were included. The number of participants in the adherence group was 9 in the adherent group, 163 in the partially‐adherent group, and 31 in the non‐adherent group. Statistical analysis showed that the adherent group exhibited a significant interventional effect compared to the control group (MD = 0.266, p = 0.025), while no significant mean difference was observed between the other adherence group and the control group.ConclusionOur findings suggest that supporting adherence is important to achieve the sufficient effect of multidomain interventions.
Biomarker‐guided clustering in an Amish population older than 60 reveals subgroups featuring distinct Alzheimer Disease pathologies
Authors: Wang Ping , Song Yeunjoo E. , Lynn Audrey , Miskimen Kristy L. , Prough Michael B. , Dorfsman Daniel A. , Gulyayev Alex V. , Laux Renee A. , Fuzzell Sarada L. , Hochstetler Sherri D. , Zaman Andrew F , Adams Larry D. , Caywood Laura J. , Clouse Jason E. , Herington Sharlene D. , Whitehead Patrice L. , Liu Yining , Moore Noel C. , Main Leighanne R. , Ogrocki Paula K. , Lerner Alan J. , Griswold Anthony J. , Vance Jeffery M. , Cuccaro Michael L. , Scott William K. , Pericak‐Vance Margaret A. , Haines Jonathan L. 
Published: January 2025

AbstractBackgroundPlasma amyloid‐beta (Aβ) 42/40 ratio and phosphorylated tau 181 (pTau181) are promising blood biomarkers for AD. Compared to heterogenous clinical phenotypes, they are more objective and proximal to the pathological hallmarks of Aβ plaques and tau tangles. Biomarker‐guided clustering using Aβ42/40 and pTau181 can potentially establish subpopulations that share similar mechanisms of AD and treatment responses.MethodPlasma biomarkers were measured using Simoa™ Neuro‐3Plex, 4Plex, and pTau181 Advantage V2 assays. To eliminate potential confounding effects, age, sex, and study center were regressed out of Aβ42/40 and pTau181 using a quadratic regression model. Adjusted biomarkers were then normalized for unsupervised K‐means clustering, with the optimal number of clusters determined by the elbow method and Silhouette score. To interpret the cluster profiles, we explored the differences in demographics and clinical features between clusters. We also examined the association between clusters and neuropsychological tests adjusting for age, sex, study center, APOE e4 alleles, and diagnosis.ResultWe analyzed plasma biomarkers from 593 Amish individuals (age ³ 60 years old) living in Ohio and Indiana. 62% were females, and the average age was 81.7 ± 5.7 years. Utilizing plasma Aβ42/40 and pTau181, the clustering approach yielded six distinct clusters (N = 92, 95, 94, 152, 75, and 85) whose composition was driven by varying burdens of amyloid and tau pathology. There was no significant difference in proportion of cognitive impairment or of family structure across clusters. As expected, the low Aβ42/40 and high ptau cluster (Cluster 6) featured a significantly higher proportion of APOE e4 carriers than other clusters combined (51% vs 22%, p = 0.002). No significant associations were found between clusters and neuropsychological tests.ConclusionThe integrated analysis of plasma Aβ42/40 and pTau181 in the Amish established six clusters with varying levels of amyloid and tau burden, suggesting possible differences that need to be further explored. Examination of potential genetic or pathophysiological differences across the clusters are underway.
Exposure Severity and Cognitive Dysfunction are Mediated by Low‐Grade Cerebral Amyloidosis: A PET/MRI study of World Trade Center responders
Authors: Kritikos Minos , Zhou Juin W. , Huang Chuan , Vaska Paul , Clouston Sean A.P. , Luft Benjamin J 
Published: January 2025

AbstractBackgroundWorld Trade Center (WTC) responders endured exposures to neurotoxic dust particulate matter. This neuroimaging study examined the presence of amyloidosis in Alzheimer’s disease (AD) regions of interest (ROIs) and associations with exposure duration.MethodSimultaneous positron‐emission tomography with [18F]‐florbetaben and magnetic resonance neuroimaging was acquired on 34 middle aged WTC responders. Centiloid scale used mean standardized uptake value ratio (SUVR) with between subjects comparisons of cognitively unimpaired (n=17) and early‐onset dementia (n=17) responders. Pathway analyses investigated potential neuropathological cascades.ResultOnly one subject was Centiloid positive. However, considerable SUVRs in non‐AD ROIs associated with changes in cortical mean diffusivity, cortical thickness, cognition, and exposure duration, mediated by the olfactory bulb.ConclusionFibrillar amyloidosis may have originated in, and spread from the olfactory cortex because of prolonged exposures to WTC neurotoxic dust. Our study also identifies a non‐AD neuropathological topology of amyloidosis, which associated with lower measures of brain health.
Soda consumption and risk of dementia: The Northern Manhattan Study
Authors: Farhi Arielle , Rundek Tatjana , Agudelo Christian , Elfassy Tali , Wright Clinton B. , Elkind Mitchell S.V. , Gutierrez Jose , Gardener Hannah 
Published: January 2025

AbstractBackgroundSoda consumption has been associated with vascular risk factors and events. While diet quality is understood to impact dementia risk, little is known about soda consumption in relation to dementia. We hypothesized that regular soda and diet soda consumption were associated with an increased dementia risk.MethodWe utilized data from 959 participants in the Northern Manhattan study, a longitudinal population‐based multi‐ethnic cohort. Regular and diet soda consumption were assessed by food frequency questionnaire at baseline (1993‐2001) and examined continuously (sodas/week) and categorically. Incident dementia was adjudicated during follow‐up after a series of comprehensive neuropsychological and clinical assessments. We used logistic regression models to examine the associations between regular and diet soda consumption and risk of dementia, adjusting for demographics and vascular risk factors (body mass index, diet quality, smoking history, alcohol use, physical activity level).ResultOf 959 participants with recorded data on soda intake and neuropsychological assessments (mean baseline age 64±8 years, 40% men, 64% Hispanic, 16% non‐Hispanic White, 18% non‐Hispanic Black), 174 (18%) developed dementia over an average of 11 years of follow‐up. 4.9% of participants drank regular soda >1/day and 2.3% of participants drank diet soda >1/day. Consumption of diet soda was associated with an increased risk of dementia (diet soda/week OR = 1.04, 95% CI 1.00‐1.08), adjusting for sociodemographics and vascular risk factors. Those who consumed more than one diet soda per day had a 3.91‐fold increased risk compared to <1/day (95% CI 1.31‐11.63), and this association was especially strong for non‐Hispanic Black participants (OR = 10.01, p<0.05). The association was not apparent after excluding those with obesity or the metabolic syndrome (N = 476, diet soda/week OR = 1.03, 0.94‐1.13). An association between regular soda consumption and incident dementia was only observed after excluding those with obesity or the metabolic syndrome (regular soda/week full cohort: 1.01, 0.98‐1.04; restricted cohort: OR = 1.05, 1.00‐1.10).ConclusionThe results support a potential increased risk of dementia associated with frequent consumption of regular and diet soda, but further research is needed in diverse study populations, with great attention paid to the confounding and mediating impacts of cardiometabolic risk factors and the potential for effect modification by race.