bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moderate alcohol use, total brain volume, and white matter hyperintensities among racially and ethnically diverse middle‐aged adults
Authors: Guzmán Diana S. , Renteria Miguel Arce , Avila Justina F , Turney Indira C , Rossano Samantha , Johnson Aubrey S. , Smith Anna C. , Okafor Amarachukwu , Morales Clarissa , Gu Yian , Manly Jennifer J. , Brickman Adam M. , Lao Patrick J. 
Published: December 2023

AbstractBackgroundModerate alcohol use may provide later life cognitive benefits compared to heavy alcohol use. However, results have been mixed, with reports of both increased and decreased gray and white matter volumes with moderate drinking. Additionally, alcohol use on brain health may differ by sex and race/ethnicity. Understanding the association between brain health and moderate drinking in a representative, community‐based study will provide insight into the reported cognitive benefits. We investigated the relationship between alcohol use and total brain volume (TBV) and white matter hyperintensities (WMH) in a diverse sample of middle‐aged non‐alcohol dependent community‐dwelling adults.MethodParticipants (N = 350; Mage = 54±10 years; 33 Black Men, 38 Black Women, 66 Latinx Men, 166 Latinx Women, 7 White Men, 20 White Women) from the Offspring study of Racial and Ethnic Disparities in Alzheimer’s Disease, a community‐based study in Northern Manhattan, underwent structural (TBV = 1051±106cm3) and vascular (WMH = 3±4cm3) MRI. Alcohol use was assessed by the Alcohol Use Disorder Identification Test–Concise (AUDIT‐C). Individuals likely to be alcohol dependent (AUDIT‐C≥9) were excluded (n = 16). We assessed alcohol use and TBV or WMH, adjusting for age, in the overall group, and stratified by sex/gender groups, racial/ethnic groups, and sex/gender by race/ethnicity groups.ResultOverall, greater TBV was associated with younger age (‐3.5cm3 [‐4.7, ‐2.3], p = 9E‐10) and greater alcohol use (5.1cm3 [‐6.8, 10.8], p = 0.085). No associations were found within men and women separately. Within race/ethnic groups, greater alcohol use was associated with greater TBV only among Latinx (7.6cm3 [0.1, 15.3], p = 0.055). Within sex/gender by race/ethnicity groups, greater alcohol use was associated with lower TBV among White men (‐36.8cm3 [‐45.0, ‐28.5], p = 1E‐3). There were no associations with WMH.ConclusionModerate alcohol use was not reliably associated with brain health, but the effect was on the order of 1‐2 years of aging, in a diverse sample of middle‐aged non‐alcohol dependent community‐dwelling adults. However, moderate alcohol use may have effects on brain volume within specific sex/gender and race/ethnicity groups with implications for later life cognitive impairment. Future work should explore region specific associations, alcohol use factors (i.e., context of use, alcohol type, duration of use), and its relationship to change over time.
Co‐production in the PREVENT Next Generation Study: methodology and outcomes
Authors: Gregory Sarah , Amfo‐Antiri Auswell , Agyapong Nana Ama Frimpomaa , Davies Michaela , Danso Samuel O. , Farina Francesca R , Saunders Stina , Wells Katie , Willingham Katie , Booi Laura 
Published: December 2023

AbstractBackgroundInvolving patients and the public as stakeholders (hereafter described as contributors) in the design and management of research studies is increasingly recognised as central to conducting ethical, meaningful and translatable research. Consulting and co‐producing are two methods for involving public contributors in the research cycle. This abstract describes the methodology used to establish a co‐production model for the PREVENT Next Generation (NextGen) research program, alongside initial impact the contributors have had on the program. The NextGen research programs aims to explore brain health in young adults (aged 18‐39), and all contributors represent this age group.MethodAdverts appealing for public contributors were sent to voluntary and community sector enterprises, universities, promoted on social media and spread via word of mouth. The first round of recruitment focused on contributors living in North America and Europe, with recruitment underway in Ghana. Contributors watched an introductory video, completed a form to indicate interest and were sent an invite to a virtual meeting. The aim of the initial work was to consider and feedback on the NextGen proposal, beginning the co‐production by identifying topics of interest for inclusion in planned work.ResultPublic contributors joined the initial meetings and were supportive of the need to understand more about brain health in young adults. Public contributors were interested in exploring topics such as the role of sex differences, social relationships and air pollution on brain health. Considering the focus groups (Phase 1 of NextGen), contributors advised having a choice of times that would support adults in work or education to join, as well as expressing a preference for virtual engagement for such studies.ConclusionEmploying a public involvement and co‐production model from the initial design stage of the NextGen study has proven invaluable to identifying topics of importance to include in future studies involving this age group. Future work will continue to develop the NextGen research program work with public contributors. Expansion of the public contributors to represent different global regions is underway, and will be critical to designing an inclusive study that is meaningful to the populations from which participants are enrolled.
Manipulation of Dietary DHA does not Alter DHA Brain Uptake Kinetics in Mice Despite Changing Brain and Plasma DHA Levelsvs
Authors: Duro Marlon Vincent V. , Van Valkenburgh Juno S. , Abdullah Laila , Ingles Diana E. , Cai Zhiheng , Kerman Bilal Ersen , Wang Shaowei , Jacobs Russell E. , Sta. Maria Naomi , Zanderigo Francesca , Croteau Etienne , Cunnane Stephen , Rapoport Stanley I. , Chen Kai , Yassine Hussein N. 
Published: December 2023

AbstractBackgroundIncreased brain docosahexaenoic acid (DHA) uptake reflects a compensatory mechanism for maintaining brain DHA homeostasis and can be captured through PET‐MRI scan uptake studies using radiolabeled DHA. It has been previously shown that APOE4 status and alcohol intake alter brain DHA uptake in mice. Whether a change in DHA intake affects the brain DHA incorporation coefficient (K*) however is not known.MethodFour‐month‐old C57BL/6J mice were fed either a diet rich in DHA (15 kcal% Fat, 1.7 g/kg ALA, and 7g/kg DHA) or deficient in DHA (15 kcal% Fat and 0.9 mg/kg ALA) for 4 months. At 8 months, anesthetized mice were subjected to dynamic PET‐MRI for 30 min following i.v. injection of 22‐[18F]fluorodocosahexaenoic acid ([18F]FDHA), prepared in‐house through radiosynthesis. Using an image‐derived cardiac input function, brain uptake was assessed by estimating [18F]FDHA K* values using both the Patlak model approach and the irreversible two‐tissue compartmental model (Irr2TCM) with and without correction of the brain radioactivity for radioactive spillover from the skull. Mice were then sacrificed, and the plasma and brains were analyzed using liquid chromatography‐mass spectrometry (LC‐MS) to evaluate differences in the unlabeled concentrations of fatty acids into phospholipids, triglycerides, and other lipids.ResultThere was no significant difference in the [18F]FDHA K* estimates (with either Patlak or Irr2TCM) between mice fed a DHA‐rich or a DHA‐deficient diet. LC‐MS based lipidomic analysis showed that the DHA‐rich diet significantly increased DHA concentration in triglycerides in plasma and in phosphatidylethanolamine in the brain.ConclusionThese results suggest that under physiological conditions, increased dietary intake of DHA in wild‐type mice increases DHA in brain phosphatidylethanolamine and in plasma triglycerides without changing the DHA K*. The net effect likely is increased brain DHA uptake, equal to the product of unesterified DHA plasma concentration and K*. Imaging brain DHA with dynamic [18F]FDHA PET‐MRI is a potentially useful tool not only to investigate the APOE4 phenotype, which promotes DHA dysregulation, but also to assess dietary and pharmacological interventions that affect brain DHA homeostasis as well as to guide future treatments.
Using deep learning model on drawing tasks as a screening tool for mild cognitive impairment in older adults with sensory impairments
Authors: Chunharas Chaipat , Chatnuntawech Itthi , Ruengchaijatuporn Natthanan , Teerapittayanon Surat , Chotibut Thiparat , Raksasat Raksit , Sriswasdi Sira , Itthipuripat Sirawaj , Petchlorlian Aisawan , Chunamchai Sedthapong 
Published: December 2023

AbstractBackgroundMild cognitive impairment (MCI) and sensory impairments commonly co‐exist in an aging population (e.g., Rong et al. 2020). A previous study has shown that patients with hearing impairment tend to do worse on verbal tests (Utoomprurkporn 2020). The reason is that the patients fail to hear the task instructions and have to put in more effort which is cognitively taxing. Therefore, a non‐verbal cognitive task for MCI screening is needed.MethodWe developed a deep learning model for MCI screening which requires only drawing tasks (trail‐making task, cube‐copying task, clock drawing task) on a digital tablet as its inputs. We cross‐validated the model on 981 subjects (age 55‐89, 77% female, 29% MCI) from our healthy aging clinic. The model used VGG16 as a backbone with self‐attention layers which expect to both improve the model performance and provide visual explanations.ResultThe model can discriminate between MCI and healthy controls with an AUC of 0.84. Our model provided better visual explanations that are compatible with how experienced clinical psychologists interpret the drawings. To increase the generalizability, we further developed a second model that aims to automate the clock drawing scoring. The models were tested in patients with and without sensory impairments.ConclusionWe investigated the feasibility of our deep learning models on drawings as a potential tool for MCI screening in an aging population with sensory impairments. The tool requires little or no human clinical experience and potentially can be used as a part of the population‐based MCI screening program.
Neuropsychological assessment as a predictor of dementia conversion in Alzheimer’s disease
Authors: Goodman Zachary T , Blennow Kaj , Zetterberg Henrik , Vontell Regina T , Rundek Tatjana , Scott William K. , Llabre Maria M , Levin Bonnie , Sun Xiaoyan 
Published: December 2023

AbstractBackgroundProgressive cognitive decline is a characteristic of Alzheimer’s disease (AD). Identifying reliable predictors of conversion to dementia in older adults, particularly those with mild cognitive impairment (MCI), is critical for clinicians, patients, and patient families.Method1083 adult participants (Age: M = 73.20, SD = 6.92) were included in this study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The average follow up was over 5 years (M = 65.25, SD = 40.16). Cox proportional hazards regression models were implemented to estimate the risk of dementia. Models were built sequentially to examine changes in predictive contributions when including biomarkers and cognitive predictors.Result57% of participants were classified as MCI and 43% as cognitively normal (CN). By the end of study, there is an overall conversion rate of 24% from the participants with cognitive normal and MCI to dementia. Participants with MCI demonstrated significantly higher rates of conversion than those with CN (F(1,258) = 92.51, p < .001, η2 = .26). The initial model indicated greater age (HR = 1.03, p = .004), fewer years of education (HR = 0.95, p < .027), the presence of at least one APOE ε4 gene (HR = 3.23, p < .001), and higher levels of neurofilament light chain (NFL) (HR = 1.28, p < .001) predicted conversion to dementia. A second model indicated higher levels of Ab42 was predictive of lower risk (HR = 0.41, p < .001), whereas higher levels of P‐tau was predictive of greater risk (HR = 1.48, p < .001). APOE ε4 presence and NfL levels remained significant predictors. Finally, composites of memory and executive scores were added. Memory performance at baseline was highly associated with dementia risk (HR = 0.26, p < .001), with poorer performance at baseline predicting greater likelihood of conversion. Similarly, poorer performance on executive functioning tasks was predictive of dementia risk (HR = 0.57, p < .001).ConclusionComposite scores of memory and executive functions are strong predictors of conversion to dementia. Such composites are approximately as predictive as Ab42, and more predictive than demographics, APOE ε4 presence, baseline P‐tau and NFL.
The impact of alcohol consumption on the cognitive performance of older adults with mild cognitive impairment
Authors: Dhakal Usha , McLaughlin Sara J. , Kim Seonjin 
Published: December 2023

AbstractBackgroundCurrent evidence suggests that excessive alcohol consumption increases the risk of developing dementia and cognitive decline and that mild to moderate drinking confers protection; however, findings are mixed. In those with mild cognitive impairment (MCI), evidence concerning the role of alcohol consumption is especially limited. To enhance understanding, we assessed the impact of alcohol use on cognitive trajectories in a large sample of older Americans with MCI.MethodUsing hierarchical linear mixed modeling and data from eight waves (2004‐2018) of the Health and Retirement Study (HRS), we examined the relationship between alcohol use and cognitive functioning (sum of tests of immediate and delayed word recall, a serial seven subtraction test, and counting backwards, range: 0 to 27) among 1468 adults age 60 years and older with MCI at baseline. Model covariates included APOE, demographics, functional status, and other health and lifestyle‐related factors that are associated with dementia.ResultThe average cognitive score of older adults with MCI at baseline was 9.5. While no significant association between alcohol consumption and cognitive functioning was observed at baseline, alcohol consumption was positively associated with cognitive functioning over time. Among those who did not consume alcohol, the average cognitive score declined by 0.12 points each year (β = ‐0.12, p<0.0001). Compared to those who never drank alcohol, low to moderate (male<15 and female<8 drinks; β = 0.08, p = 0.0001) and heavy (male> = 15 and female> = 8 drinks; β = 0.13, p = 0.03) drinking were associated with more favorable cognitive performance over time.ConclusionFindings from this study suggest that alcohol consumption confers protection against cognitive decline among older adults with MCI. Future studies are needed, however, to more fully investigate how the nature of drinking (e.g., types of drinks consumed, the number of drinking years, binge drinking) may influence the relationship between alcohol consumption and cognitive performance over time.
Attitudes of smartphone‐based hearing screening test use among patients with mild cognitive impairment: A qualitative study
Authors: Limkitisupasin Patcharaorn , Utoomprurkporn Nattawan , Tangwongchai Sookjaroen 
Published: December 2023

AbstractBackgroundWhile the importance of early diagnosis of hearing loss in older adults with cognitive impairment has been increasingly highlighted, smartphone‐based self‐hearing assessments have become widely adopted due to their low cost, easy‐to‐use, and accessibility. The validity and reliability of this method have been accepted for detecting hearing loss. However, few studies were conducted on this vulnerable population. The purpose of this qualitative study was to explore older adults with mild cognitive impairment’s experiences, perceptions, and attitudes toward digital self‐hearing screening tools.MethodSeventeen patients with mild cognitive impairment (MCI) were recruited from memory clinic in Bangkok, Thailand. Focus groups were conducted to understand self‐perception of hearing problems and their experience after using smartphone‐based hearing screening application. Thematic analysis was used to analyze the data.ResultAll focus groups discussed self‐perception of hearing loss, experience of use, as well as feedback for smartphone‐based hearing screening application. The acceptability and attitude of smartphone‐based hearing test was explored. Individual experiences varied depending on personal factors and lifestyle.ConclusionDigital self‐hearing screening tools emerged as potential method for screening hearing impairment. The findings of this study described opinions, feedback, and factors that contributed to the usage of smartphone‐based hearing screening applications. These findings will inform further developments of this tool based on the personalized needs of individuals with cognitive impairment, with the objective of facilitating the early detection and timely intervention for hearing loss in this population.
The synaptic biomarker contactin5 differentiates between neurodegenerative dementias
Authors: Gouda Mariam , Muqaku Besnik , Hok‐A‐Hin Yanaika S. , in ’t Veld Sjors G.J.G. , Verberk Inge M.W. , Otto Markus , Teunissen Charlotte E. , Oeckl Patrick 
Published: December 2023

AbstractBackgroundSynapses are crucial for memory formation, and their disruption is among the earliest events in Alzheimer’s disease (AD) pathogenesis. Less is known about synaptic alterations in other types of dementia. Contactin5 (CNTN‐5) is a synaptic protein and one of the neural adhesion molecules. It contributes to synaptic formation, plasticity and is associated with dendritic morphogenesis. A GWAS identified a risk variant (rs 141684 G) in CNTN‐5 gene, which is associated with increased risk of AD development. We aimed to assess whether CNTN‐5 could be a differential diagnostic cerebrospinal fluid (CSF) biomarker for AD from other types of dementia.MethodCNTN‐5 levels in CSF samples were measured with two methods: an in‐house developed immunoassay on the automated ELLA platform, and a multiple reaction monitoring mass spectrometry (MRM) assay. The clinical cohort included controls (n = 27), patients with AD (n = 19), patients with behavioral variant frontotemporal dementia (bvFTD) (n = 18), and patients with dementia with Lewy bodies and Parkinson’s disease dementia (PDD/DLB) (n = 18; table 1). CNTN‐5 results obtained with both methods were correlated using spearman’s correlation. Differences in CNTN‐5 levels between the diagnostic groups were assessed with Kruskal‐Wallis test and corrected with Dunn´s factor for multiple comparison.ResultsAs shown in Figure 1, CNTN‐5 measurements between methods were strongly and positively correlated (rho = 0.58, p<0.001). In AD patients, CNTN‐5 levels were significantly elevated in comparison to bvFTD patients with both assays (both: p<0.05), as well as, compared to patients with DLB/PDD (MRM: p<0.05 and ELLA: p<0.01). There was no significant difference in CNTN‐5 levels between AD and controls, or between bvFTD and PDD/DLB, as shown in figure 2.ConclusionOur results showed that elevated CNTN‐5 is a promising synaptic biomarker, with specificity for AD. As a next step, we would look further into a larger clinical cohort, where associations between CNTN‐5 levels and cognitive stage could be thoroughly studied.
Culturally relevant protective factors and relationships with cognitive decline in First Nations Australians
Authors: Lavrencic Louise , Mack Holly , Withall Adrienne , Delbaere Kim , Broe Gerald A , Daylight Gail , Draper Brian , Lasschuit Danielle , Radford Kylie 
Published: December 2023

AbstractBackgroundFirst Nations people in Australia experience dementia prevalence 3‐5 times higher than the broader Australian population. There is strong focus on risk factors (particularly biomedical) in dementia research; yet further research is required to understand protective factors, especially psychosocial and cultural determinants. Cognitive reserve (CR) refers to the brain’s adaptability when faced with age or neurodegenerative‐related changes. CR is important for understanding cognitive outcomes and dementia onset. Psychosocial factors are thought to contribute to CR, including education and work opportunities. Yet, the appropriateness of conventional CR measures for First Nations people, and the role of culturally‐specific protective factors in CR, is unclear.MethodData were from the Koori Growing Old Well Study, a longitudinal, population‐based study with First Nations Australians aged 60+ from 5 rural/urban communities in New South Wales (N = 336 baseline; N = 165 6‐year follow‐up, n = 68 died before follow‐up). Comprehensive and holistic interviews were carried out. Dementia and mild cognitive impairment (MCI) were based on clinical assessment and consensus review. CR factors spanned education and work opportunities, sociocultural activities/connections, creative hobbies, playing sports, and social contact. Logistic regression analyses were used to examine factors at each life stage (early/mid/late‐life) in relation to cognitive decline (incident MCI/dementia).ResultThe analyses included 155 participants (excluding N = 10 with baseline dementia). Of the early‐life factors, singing (from the Retrospective Indigenous Childhood Enrichment Scale) (OR = 0.33; 95% CI 0.13, 0.86; p = .024) was associated with a lower risk of cognitive decline in the multivariable model; and years of education (OR = 0.79; 95% CI 0.66, 0.94; p = .008) predicted cognitive decline in univariable analysis. For midlife, history of unskilled work was associated with cognitive decline (OR = 5.44; 95% CI 2.32, 12.75; p = <.001). No variables in the late‐life model were significantly associated with cognitive decline.ConclusionThis study is the first to examine factors that may contribute to CR in First Nations communities, including culturally‐specific items. These results suggest that certain life‐course experiences may protect against cognitive decline; however, revised and sensitive measures are needed to capture nuanced differences. A culturally relevant and more comprehensive CR measure is currently being piloted with First Nations people.
Discovery of farnesyltransferase inhibitors (FTIs) with high brain exposure for treatment of Alzheimer’s disease and other tauopathies (T‐PEP Related Presentation)
Authors: Olson Steven 
Published: December 2023

AbstractBackgroundFarnesyltransferase (FTase) is a prenyltransferase enzyme that adds farnesyldiphosphate to the cysteine of CaaX proteins. Compelling evidence suggests that FTase inhibitors (FTIs) cause lysosome activation and a dramatic increase in tau degradation (Hernandez, et al. Science Translational Medicine 11.485 (2019): eaat3005)MethodNovel small molecule inhibitors of FTase were synthesized and tested in a luminescence‐based enzymatic assay of FTase inhibition. Active compounds were tested in ADME assays including MDCK‐MDR1 cells to evaluate permeability and transporter‐mediated efflux. Optimized compounds were evaluated in pharmacokinetics and in vivo pharmacodynamics (PD) experiments measuring enzymatic farnesylation of farnesyl alcohol azide in the mouse brain.ResultWe report the first highly brain‐penetrant FTase inhibitors. These compounds show nanomolar potency and achieve high exposure in both plasma and brain. PD experiments show that the compounds inhibit farnesylation in the CNS of our mouse modelConclusionBrain penetrant small molecule FTase inhibitors show promising preclinical pharmacology and are currently in the lead optimization stage of drug discovery.