bluuebunny/crossref_metadata_2025_split huggingface dataset:
Green, Blue, Brown, Gray? Nature exposure and cognitive function among aging Mexican Americans
Authors: Darwish Hala J , Hokett Emily , Tureson Kayla N , Allan Alexa C , Finlay Jessica M , Webster Noah J 
Published: January 2025

AbstractBackgroundStudies link nature exposure to better cognitive health outcomes. However, little is known about which types or ‘how much’ of nature is needed for health benefits. Studies often lack diverse aging populations and have small sample sizes.MethodOur study investigated the relationship between land cover types (e.g., water, green, developed, or barren) and cognitive function (Mini Mental Status Exam) in 2,069 participants from the Wave 5 Hispanic Established Population for the Epidemiological Study of the Elderly. Linear mixed‐effect models adjusted for individual (e.g., age) and area‐level (e.g., poverty) covariates were used.ResultThe mean age was 81.9±5.2, 61.5% women, and the mean years of education was 4.9±4.0. The median MMSE score was 22, range of 0‐30. Latent Profile Analysis of land cover types revealed four distinct classes. Individuals living in less developed, green‐mix areas had higher cognitive scores, particularly among women.ConclusionEnvironments with a mix of nature and access to services, amenities, and other people positively impact cognition in aging Mexican American women.
Using TAS Test online hand‐tapping tests to detect cognitive decline in a large community cohort of older Australians
Authors: Alty Jane E , Wang Xinyi , Bindoff Aidan , George Rebecca J St , Roccati Eddy , Bartlett Larissa , Lawler Katherine , Noyce Alastair J , Tran Son , King Anna E , Bai Quan , Vickers James C 
Published: January 2025

AbstractBackgroundFinding low‐cost, accessible methods to detect people with early‐stage Alzheimer’s disease is a research priority for neuroprotective drug development. Subtle motor impairment of gait occurs years before episodic memory decline but there has been little investigation of whether self‐administered hand motor tests can detect this pre‐symptomatic period. This study evaluated how home‐based unsupervised keyboard tapping tests from the TAS Test protocol predict episodic memory performance in a sample of older adults without overt cognitive impairment, as a potential indicative measure of early Alzheimer’s disease.Method1,140 community participants (65.7 ± 7.4 years old; 73% female) without cognitive impairment from the ISLAND cohort study completed a 40‐second single key tapping test, a 60‐second alternate key tapping test, and a 40‐second sequence tapping test from TAS Test. Participants also completed validated CANTAB cognitive tests of episodic memory, working memory and executive function. Frequency, variability, key press duration and accuracy scores were calculated for each tapping test. Generalized linear models examined associations between keyboard tapping and cognitive performance, adjusted for confounders including age, sex, depression, anxiety and education.ResultCombination of motor features of the single key (R2
adj = 8.0%, ΔAIC = 3.7), alternate key (R2
adj = 7.9%, ΔAIC = 2.8), and sequence tapping tests (R2
adj = 8.2%, ΔAIC = 8.4) improved estimation of episodic memory performance relative to models with demographic and mood confounders only (R2
adj = 7.3%). Only tapping features of tests involving sequence tapping (R2
adj = 6.3%, ΔAIC = 2.5) improved estimation of working memory. Tapping features of single key tapping tests (R2
adj = 15.8%, ΔAIC = 8.3) and sequence tapping tests (R2
adj =16.5%, ΔAIC = 13.7) improved the estimation of executive function performance.ConclusionBrief unsupervised and self‐administered online keyboard tapping tests predict asymptomatic episodic memory decline in a sample of older adults. This provides a potential low‐cost and brief home‐based method for risk stratification of enriched cohorts for further assessment.
Gender difference in cognitive functioning varies by level of purpose in life – Results of the New Zealand Health, Work and Retirement (NZHWR) study
Authors: Röhr Susanne , Gibson Rosemary , Alpass Fiona 
Published: January 2025

AbstractBackgroundHigh purpose in life – the extent of engagement in activities that are personally valued and give a sense of direction and meaning to life – has been associated with higher cognitive functioning and may protect against dementia. Less is known about gender differences in cognitive functioning regarding purpose in life. Understanding gender‐specific links can inform tailored interventions aimed at promoting cognitive health.MethodA subsample (n = 875, aged 50‐85 years) of the NZHWR study completed face‐to‐face cognitive assessments and postal surveys in 2012. Cognitive functioning was assessed with Addenbrooke’s Cognitive Examination–Revised (ACE‐R), adapted for culturally acceptable use in New Zealand. Purpose in life was measured with the Life Engagement Test. Linear regression analysis assessed associations of gender, purpose in life and their interaction with cognitive functioning, controlling for socioeconomic factors (age, age², education, ethnicity [Māori, Indigenous people of New Zealand, and Non‐Māori, mostly of European descent], marital status, employment, individual‐level economic hardship, area‐based socioeconomic deprivation), lifestyle and health factors (smoking, alcohol consumption, physical activity, SF‐12 physical and mental health, social engagement, social loneliness).ResultThe analytical sample (n = 643) was M = 65.3 (SD = 7.4) years old; 53.3% women, 21.2% Māori. The ACE‐R score was M = 92.9 (SD = 5.3). N = 55 (8.5%) scored ≥1.5SD below the mean, indicating cognitive impairment. Women had higher cognitive functioning (M = 93.7, SD = 4.6 vs. M = 92.0, SD = 5.8; Z = ‐3.88, p<.001) and purpose in life (M = 26.2, SD = 3.8 vs. M = 25.8, SD = 3.4; Z = ‐2.19, p = .029) than men. In the adjusted regression analysis (R² = 27.6%), higher purpose in life (B = 0.29, 95%CI = 0.12;0.46; p = .001) and female gender (B = 9.97, 95%CI = 4.71;15.24, p<.001) were associated with higher cognitive functioning. The association of purpose in life with cognitive functioning was less pronounced for women than men (B = ‐0.31, 95%CI = ‐0.51;‐0.11; p = .003) (Fig. 1). Significant covariates included age², education, deprivation, and social loneliness.ConclusionIn this sample of older New Zealanders, a gender difference in cognitive functioning varied by level of purpose in life. Women had higher cognitive functioning than men, particularly at lower purpose in life, with the difference decreasing as purpose in life increases. Interventions to enhance purpose in life might particularly benefit men. Notably, cognitive functioning may also impact purpose in life, emphasising the need for longitudinal studies.
Influence of in vivo Hsp90α inhibition on irisin signaling to the brain
Authors: White Zachary J , Sudasinghe Keshari , Weber Ramona , Hall Stephanie E 
Published: January 2025

AbstractBackgroundIrisin is an exercise‐induced myokine that elicits beneficial effects of exercise in fat, bone, and the brain. Previous work suggests that extracellular heat shock protein 90a (Hsp90a) mediates irisin‐receptor interaction in bone and fat. Despite this, it remains unclear if Hsp90a is necessary for irisin signaling in the brain.MethodsFemale F344 rats (3‐4 mo, n = 32) were randomized into four treatment groups: irisin + Hsp90a inhibition (IX, n = 10); irisin + vehicle o.g. (IC, n = 10); vehicle i.p. + Hsp90a inhibition (CX, n = 6) and; vehicle i.p. + vehicle o.g. (CC, n = 6). Due to the impact of irisin on memory, a novel object recognition test was conducted over 4 days. Days 1‐2 were habituation, day 3 was familiarization, and day 4 was testing. Directly following NOR day 2, animals received single administrations of irisin (100 mg/kg, i.p.) or vehicle control and selective Hsp90a inhibitor SNX‐5422 (10 mg/kg, o.g.) or vehicle control. Day 4 NOR testing and tissue collection occurred 48 hours following drug administrations. Blood was collected via LV puncture, centrifuged to isolate serum, and stored at ‐80°C. Brains were sectioned, weighed, and snap‐frozen in liquid nitrogen. The downstream target of irisin signaling, hippocampal cyclic‐AMP Response Element Binding Protein (CREB) was quantified via Jess Simple Western automated western blot analysis. Hippocampal BDNF and serum irisin were quantified via ELISA. Values are mean ± standard deviation.ResultsIn the NOR task, the IC group displayed a preference for the novel object (68.77 ± 17.93% of exploration time with novel object; p<0.01, one‐sample t‐test vs 50%). Novel object preference was not displayed in other groups. Hippocampal total CREB was greater in the IC than in the CC group (11.0 ± 0.85 vs 9.4 ± 0.80 a.u.; p<0.05, one‐way ANOVA). No differences in tissue masses, levels of hippocampal phosphorylated CREB, p/t CREB, and BDNF or serum irisin were present between groups 48 hours following dosing.ConclusionsThis investigation supports irisin signaling to promote memory function and indicates a mediating role of Hsp90a in the brain. Further analysis of hippocampal mRNA is needed to understand the influence of Hsp90a inhibition on irisin‐mediated transcriptional changes.
Media Contribution to Dementia Awareness in Recruitment and Retention of Alzheimer’s Disease Diversity Genetic Cohorts‐ Alzheimer’s disease Sequencing Project in Africa
Authors: Farombi Temitope Hannah , Arulogun Oyedunni , Nichols Michelle , Olorunsogbon Olorunyomi F , Kumolu Timilehin , Ogunronbi Mayowa , Sanni Taofeek Adedayo , Mutiso Victoria , Uthman Muhammed , Sule Abdullateef , Assey Emmanuel , Mwombeki Innocent , Onoria Joy , Onunka Godspower Chibuke , Tagoe Benedict , Melkamu Selem K , Adigwe Ifeoma , Ogunyemi Adedoyin O , Gyabaah Solomon , Byrd Goldie S. , Ogunniyi Adesola , Pericak‐Vance Margaret A , Akinyemi Rufus O. , Consortium Africa Dementia 
Published: January 2025

AbstractBackgroundThe escalating prevalence of dementia in Africa, propelled by rapidly ageing population, necessitates innovative approaches to raise awareness and address associated challenges. The prevalent misconception of dementia as a result of witchcraft or wizardry is a challenge, and the media acts as a key agent in dispelling such myths. By reaching divers audiences, the media reinforces the notion that dementia is not confined to Africa alone but it is a global concern. It also aids in overcoming the shame and stigma associated with dementia, encouraging individuals to seek consultation.MethodA comprehensive analysis of media initiatives used by the African Dementia Consortium (AfDC) during the World Alzheimer’s Month and subsequently was conducted. Digital Platforms (Instagram, LinkedIn, Facebook), print and traditional media (publications, journals, newspaper, radio and television stations) were examined for their effectiveness in achieving recruitment objectives, destigmatizing and promoting early diagnosis. Quality tools, such as cameras and recorders, were utilized to capture relevant information, while the outcome was evaluated based on their impact on target audience assessed by greater participation.ResultMedia Platforms have proven instrumental in recruitment efforts by disseminating information that reaches diverse demographic groups in Africa. Through compelling visual and textual content, the media has played a key role in destigmatizing dementia, challenging prevalent misconceptions, and fostering a more inclusive understanding of the condition. In addition, media initiatives have contributed significantly to the promotion of early diagnosis by disseminating educational content that empowers individuals to recognize early signs and seek timely medical intervention.ConclusionBoth the digital and traditional media play vital roles in visually and textually representing dementia, correcting misconceptions, and fostering understanding. Allocating increased resources to media initiatives hold immense benefit for Africa, contributing to a more positive perspective on dementia and dispelling negative attitudes.
How Does the Latest Clinical Pharmacology Data & Modeling Support Continued Lecanemab Dosing?
Authors: Reyderman Larisa , Willis Brian A. , Penner Natasha , Charil Arnaud , Dhadda Shobha , Hersch Steven , Irizarry Michael C. , Kramer Lynn D 
Published: January 2025

AbstractLecanemab is a humanized IgG1 monoclonal antibody binding with high affinity to protofibrils of amyloid‐beta (Aβ) protein. In 18‐month clinical studies, lecanemab has been shown to reduce a complex group of protein interactions associated with early symptomatic Alzheimer’s disease (AD) and slow decline on clinical endpoints of cognition and function for up to 30 months to date. In prior research, results from the phase 2 study gap period (no study drug treatment) between the end of the study core and the beginning of retreatment in the open‐label extension (OLE) provides evidence regarding the need for continued maintenance therapy beyond 18 months. Clinical pharmacology data can help supplement the clinical and mechanistic data to establish the rationale for ongoing treatment. Herein, we will present how the latest clinical pharmacology data and modeling support continued long‐term maintenance lecanemab dosing. Data from the lecanemab phase 2 study (Study 201) and Clarity‐AD (Study 301) were pooled, and biomarker, amyloid PET, and CDR‐SB scores were used to develop models describing the change in amyloid PET and plasma biomarkers with lecanemab treatment. A model was also developed to show how change in amyloid PET predicts slowing of disease progression. These models were used to explore the change in plasma biomarkers, amyloid PET, and CDR‐SB over 4 years, and to evaluate the effect of transitioning to less frequent dosing of lecanemab following 18 to 24 months of initial treatment. Simulations projected that CDR‐SB difference between lecanemab and placebo subjects continued increasing over the 4‐year simulation period. Low amyloid and less severe disease at baseline were associated with slower disease progression. Continued treatment with lecanemab at less frequent dosing intervals following an initial treatment period was demonstrated to effectively maintain the benefit associated with lecanemab treatment on plasma biomarkers, amyloid PET, and clinical outcomes as compared to the initial dosing regimen. We will offer learnings from these recent analyses into the ability of amyloid reduction to be predictive of slowing Alzheimer’s disease progress, the importance of early initiation of treatment, and the utility of continued lecanemab maintenance treatment.
Specific Neuroimaging Signatures of Superagers in an Urban Indian Ageing Cohort
Authors:   Sandhya G ,   Monisha S , Singh Sadhana , Lingegodwa Abhishek Mensegere , Issac Thomas Gregor 
Published: January 2025

AbstractBackgroundDecline in cognitive functioning is one significant change that occurs as people age. But, certain individuals in the community have their cognitive functioning on par with people 20‐30 years younger than them. Such individuals above the age of 80 are referred to as superagers. Previous studies identified higher brain volumes in superagers compared to typical agers. The present study aims to identify superagers in an urban Indian cohort and compare their imaging parameters with those of typical agers.MethodThe study used baseline data from Tata Longitudinal Study of Ageing (CBR‐TLSA). The 65 octogenarians of the cohort were screened based on the Northwestern criteria for superagers. The criteria includes one memory test score being equal to or greater than the mean of 50‐65‐year‐old gender and education‐matched controls, and scores in three tests of other cognitive domains not being less than 1 standard deviation of the octogenarian group. Neuroimaging was performed for a subset of the octogenarians using a 3 Telsa MR scanner. Generalised linear models were used to identify associations of brain region volumes with cognition after adjusting for total intracranial volumes.ResultA total of 14 superagers were identified in the TLSA cohort based on the criteria mentioned. Superagers were found to have significantly larger right (p = 0.01) and left hippocampus (p<0.001) owing to better memory scores in them. The total volumes of cortex (p<0.001), cerebral white matter (p = 0.02), brain stem (p = 0.037) and subcortical grey matter (p = 0.01) were greater in superagers. The right (p = 0.024) and left thalamus (p = 0.014), right cerebellum cortex (p = 0.048) and left cerebellum white matter (p = 0.025) volumes were also found to be significantly higher in superagers when compared with typical agers.ConclusionThe results identified higher volumes of specific brain regions across both hemispheres among superagers as compared to typical agers. Further, studies on superaging from healthy ageing cohorts are necessary to identify factors contributing to cognitive reserve.
Intervening paths: A dual networks approach to modifiable dementia risk in healthy older adults
Authors: Brady James J R , Bartlett Larissa , Bindoff Aidan , Norris Kimberley , Roccati Eddy , Vickers James C , Sinclair Duncan 
Published: January 2025

AbstractBackgroundMulti‐domain initiatives which target modifiable, lifestyle‐associated, dementia risk factors are promising tools for dementia prevention. However, those at greatest risk of preventable dementia likely have the least capacity to enact change. Interventions may improve outcomes for those most vulnerable by looking up‐stream. Doing so may identify targets of intervention which influence modifiable dementia risks. Applying an emerging method, we reveal candidates for targeted intervention using partial correlation and direct‐path machine‐learned networks.MethodObservations from the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Resilience Initiative (n = 1225) were sourced from the longitudinal ISLAND Study of adults over 50. Regularized partial correlation network (RPCN) was plotted with demographic and dementia risk factors using glasso and extended Bayesian Information Criteria. Removing missingness, we systematically selected nonparanormal data transformation and a H2PN algorithm to bootstrap 10,000 Bayesian networks. Our directed acyclic graph (DAG) comprised connections averaged across at least 85 per‐cent of the bootstraps. DAG network stability was tested by incrementally diminishing number of observations. Common, highly connected, and intervenable variables which led to most‐influenced modifiable dementia risks were identified by contrasting the DAG and RPCN.ResultRPCN showed modifiable risk domains of depression, cognitive activity, and MIND diet adherence were most influenced by partially correlated factors. As revealed by the DAG, pathways leading to depression included a direct link from social support availability, and indirect links from age through anxiety and the stress variables, excepting PSS’s unable to cope subscale. Gender and social subscales, except interaction frequency, led to cognitive activity, and dietary adherence (through cognitive activity and BMI). Of the up‐stream variables, identified links between stress, anxiety, and depression were the strongest, visible as thicker connections in the RPCN.ConclusionWe present candidates for focused intervention, demonstrating utility of an emerging dual‐network technique. We unveil a complex RPCN network, highlighting modifiable dementia risk factors most influenced by correlated variables. Combining the DAG’s machine‐learned pathways with the RPCN, we provide support for targeting symptoms of stress and anxiety, and fostering improved social connectivity and quality, to address dementia risk associated with levels of depression, cognitive activity, and MIND diet adherence.
Methods and Initial Data for A Massive Real‐World Deeply Phenotyped Cohort Study
Authors: Ritchie Craig W , Harrison John E , Welstead Miles , Milne Joseph , Green Alison , Doran Clara , Hussain Zain , Kaminioti‐Dumont Laura , Lan Andrew , Nadeem Ayeda , Noonan Tara , Poon Azin , Rannikmäe Kristiina , van der Westhuizen Tanya , Gregory Sarah 
Published: January 2025

AbstractBackgroundRecent therapeutic successes in the treatment of Alzheimer’s disease (AD), and diagnostic tools such as blood‐based biomarkers, have energised the field to develop more specific diagnostics and therapies following the best principles of precision medicine. Large, ‘real‐world’ cohorts are needed to understand whether these, and other future breakthroughs, are valid when employed in the wider AD community.MethodsOur cohort study will provide a well‐phenotyped (combining data on risk factors for neurodegenerative disease, cognitive assessment results, disease biomarkers and genetics) population aged 50 and above across the spectrum of risk for, and the earliest disease stages of, neurodegeneration (beginning in Scotland). Participants complete an innovative cognitive testing battery (combining elements of the ACE‐R (including MMSE), TICS, RBANS and digital cognitive tests), assessments of global functioning, questionnaires about risk factors for neurodegenerative disease, physical health assessments and collection of blood samples for clinical blood tests and storage for future research. A sub‐set of participants are invited to join the Enhanced Phenotyping cohort and additionally undergo brain MRIs and lumbar punctures. Cerebrospinal fluid will be analysed for amyloid beta‐42, phosphorylated tau‐181 and total tau, with additional aliquots stored for future research use. Participants will be followed up every 6 months to complete questionnaires, with more comprehensive visits annually. A minimum of 3000 participants will be recruited to the Enhanced Phenotype cohort with an estimated 7,000 in the cohort overall.ResultsA total of 11 participants have been recruited to the cohort to date (mean age: 69 years; 6 (55%) female). Mean ACE‐R and MMSE scores are 92 and 28 respectively. Data collection is ongoing with recruitment anticipated to continue throughout 2024 and 2025, with a minimum of 100 participants recruited by July 2024. Baseline data, including AD biomarker status where available, will be presented at AAIC 2024.ConclusionThis an ambitious project aiming to recruit a deeply phenotyped, real‐world representative cohort of participants across the spectrum of risk for, and in the earliest stages of, neurodegenerative conditions. The data and samples collected as part of this cohort will be invaluable to better understanding disease trajectories, and developing and testing new diagnostics and therapeutics.