bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Growing up we’re taught about physical activity, but very little mention of brain health, but it’s all brain health”: Exploring the Conceptualisation of Brain Health in 18–39‐year‐olds in Europe and North America
Authors: Booi Laura , Wells Katie , Gregory Sarah , An Hosanna , Marquez Melissa , Farina Francesca R 
Published: December 2023

AbstractBackgroundIt is widely theorised that the accumulation of risk factors for neurodegenerative diseases like Alzheimer’s and other dementias likely begins during young adulthood, yet there is limited understanding about how young adults conceptualise their own brain health. The NextGen research programs aims to explore brain health and exposure to risk factors in adults before mid‐life. In this study, we explored young adults’ (18‐39 years) understanding and attitudes towards their brain health.MethodsThis qualitative study recruited community‐based adults aged 18‐39 years from the NextGen Programme of research, a large‐scale, international, multi‐centre research programme. Participants (N = 39; 18 female) had a mean age of 26 years (SD = 3.68) and were equally represented from North America (n = 20) and Europe (n = 19). Most participants identified as Black (76%), followed by White (15%), Asian (6%) and mixed race (3%). Data collection took place over focus groups using video conference technology and a semi‐structured discussion guide. A live Illustrator was present for each focus group to provide an immediate visual output of the group discussion. Data were analysed using thematic analyses by the research team.ResultsPreliminary themes highlight discrepancies between individuals’ awareness and understanding of their brain health, in relation to their general health, family history of dementia and personal experience of brain health issues (e.g., traumatic brain injury). Regarding factors that can positively affect brain health, participants highlighted the importance of rest, good nutrition and physical exercise. Regarding factors that can negatively affect brain health, participants highlighted exposure to racism and discrimination, poor quality sleep, stress, and excessive alcohol consumption. Participants also reported being unsure about many factors, such as screen‐time, cannabis use, engagement with social media and video games.ConclusionFindings from this study are among the first to explore young adults’ perceptions around brain health. We found that young adults had a moderate level of awareness of brain health risk factors, but they often did not connect these factors to risk of Alzheimer’s disease or other dementias. Outputs from this study will be used to inform a large‐scale, international survey to explore brain health awareness, understanding and exposure to risk factors among 18‐39‐year‐olds.
Translational investigation of apathy and affective symptom hub genes in Alzheimer’s disease
Authors: Dunn Jeffrey T , Keszycki Rachel M , Fisher Daniel W , Rodriguez Guadalupe , Bennett David A. A , Wilson Robert S. , Dong Hongxin 
Published: December 2023

AbstractBackgroundApproximately 90% of Alzheimer’s disease (AD) patients experience at least one neuropsychiatric symptom (NPS) over the course of disease progression. However, little is known about the neural mechanisms underlying NPS in AD, leaving treatment options for these symptoms underdeveloped. Here we use a translational approach to refine hub gene candidacy for the two most common NPS domains in AD (i.e., apathy, affective) and identify targets for investigation of causal relationships between genes and behavior.MethodWeighted gene co‐expression network analysis (WGCNA) was performed on RNA‐sequencing data from human postmortem anterior cingulate cortex of 60 individuals with AD and antemortem clinical evaluations of NPS. Human and mouse protein‐protein interaction networks (PPIs) were constructed from WGCNA modules that significantly correlated with NPS domains. Expression levels of potential hub genes discovered in humans were measured in the prefrontal cortex (PFC) of 16‐month‐old wild type (WT) and 5xFAD mice by RT‐qPCR and correlated with composite z‐scores for representative apathy‐ and affective‐like behaviors.ResultWGCNA revealed that a microglial phagocytic pathway and complement cascade module was uniquely correlated with apathy. PPI analyses refined the list of 43 WGCNA potential apathy hub genes to 21 candidate hub genes suitable for translational investigation. Further, human and mouse PPI analyses identified TYROBP as the highest‐ranking apathy hub gene. Expression levels of Tyrobp were significantly higher in the PFC of 5xFAD mice than in WT controls and positively correlated with apathy z‐scores. Only two genes retained affective domain hub gene candidacy (Tgfb1 and Nfkbia) in mice. Whereas Tgfb1 expression was elevated in the 5xFAD PFC, Nfkbia was not differentially expressed. Z‐scores for affective‐like behavior did not significantly correlate with either Tgfb1 or Nfkbia expression levels.ConclusionOur results suggest that the complement system is uniquely implicated in cases of AD with apathy; Tyrobp is a strong candidate gene for the regulation of that relationship. 5xFAD mice are an appropriate model for future investigation of Tyrobp‐complement‐apathy mechanisms in AD. Further study is needed to evaluate Tgfb1 and Nfkbia as possible regulators of affective behavior in models that exhibit other AD pathology(s) (e.g., tau) alone or in conjunction with pathologic amyloid‐beta.
CSF Abeta 3‐42/1‐42 ratio and neurogranin as biomarkers of interest in dementia with Lewy bodies
Authors: Pillai Jagan A. , Popp Whitney , Bekris Lynn M. , Wang Ming , Lerner Alan J. , Leverenz James B , Miyagi Masaru 
Published: December 2023

AbstractBackgroundDementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the among the most common neuropathologies. Amyloid and tau biomarker changes are often incorporated in the clinical diagnosis of AD. The current DLB criteria does not include robust biofluid biomarkers. However differences in amyloid plaque and CSF neurogranin in DLB has been of interest based on neuropathology and prior CSF reports. Our objective was to determine if Abeta modifications Abeta 3‐42 and Abeta 1‐42 along with neurogranin could be used to differentiate DLB from AD.MethodThis cohort study among 45 MCI stage of AD meeting NIA/AA 2011 criteria and 15 DLB participants meeting the 2017 Mc Keith criteria. We evaluated the CSF levels of Abeta 3‐42, Abeta 1‐42 by Liquid chromatography‐mass spectrometry (LC‐MS/MS) techniques and CSF neurogranin by standard ELISA to explore the differences between groups. Two sample t‐tests both without and with data imputation for samples not meeting lower levels of detection and linear regression models by considering the confounding variables of age, sex and education were assessed.ResultMean age 67.67 (SD5.13) years, 33% Female. Mean neurogranin levels in DLB 325.9 (SD 200.34 were lower than in MCI‐AD 707.7 (SD 489.94) pg/ml, (p = 0.0006 from two‐sample t‐test). Mean levels of Abeta 3‐42 were 51.63(SD = 19.6) and 43.63(SD = 13.5)fmol/l, and Abeta 1‐42 848.7 (SD = 248.4) fmol/l and 981.5(SD = 265.0) in DLB and MCI‐AD, respectively and were not significantly different. The ratio of Abeta 3‐42/Abeta 1‐42 was higher in DLB 0.06 (SD = 0.02) than MCI‐AD 0.04 (SD = 0.01) (p = 0.008 from two‐sample t‐test). In the multivariable regression models after adjusting for confounding variables the ratio of Abeta 3‐42/Abeta 1‐42 (Est = 67.19,SE = 29.62, p = 0.02) and neurogranin (Est = ‐0.0069,SE = 0.0026,p = 0.009) were significant discriminators between DLB and MCI‐AD .ConclusionHigher ratio of CSF Abeta 3‐42/Abeta 1‐42 and lower CSF levels of neurogranin were noted in the DLB group compared to MCI‐AD. Lower levels of CSF neurogranin in DLB has been reported, while higher ratio of CSF Abeta 3‐42/Abeta 1‐42 in DLB is a novel biomarker finding. Differences in Abeta species in DLB could be potential biomarkers in separating DLB from AD.
Detecting Alzheimer’s risk with cognitive dispersion on neuropsychological testing
Authors: Lee Athene KW , De Vito Alyssa N. , Leng Xiaoyan , Farias Sarah Tomaszewski , Sachs Bonnie C. , Chan Michelle L , Snyder Heather M , Baker Laura D , Papp Kathryn V. ,   The U.S. POINTER Neuropsychology Team for the U.S. POINTER Study Group
Published: December 2023

AbstractBackgroundCognitive dispersion refers to the within‐person variability across tasks. Relative to the normative approach, cognitive dispersion may be more sensitive to subtle changes in preclinical Alzheimer’s disease. Greater dispersion has been associated with increased risk for conversion to mild cognitive impairment and faster rates of medial temporal lobe atrophy. This metric can be derived from a regular neuropsychological assessment and complement traditional outcome approaches, particularly in those underrepresented in normative data. This study evaluated cognitive dispersion as an independent predictor of clinical status across racial and ethnic groups.MethodBaseline data on 1811 cognitively unimpaired older adults with high vascular risk from the U.S. POINTER multisite lifestyle intervention study were examined. Sample characteristics included mean age of 68 (SD = 5.2), 70% female, 30% less‐than‐college education, and 29% underrepresented groups (301 Black, 231 Other). Correlations between cognitive dispersion and other brain health risks (vascular, subjective cognitive decline (SCD), physical activity) were tested. Cognitive dispersion was defined as the standard deviation of individuals’ z‐transformed scores of 8 cognitive tests. Vascular risk burden was the sum of 5 conditions (hypertension, diabetes, hypercholesterolemia, heart disease, obesity). Self‐report SCD was measured by the Cognitive Function Instrument (CFI) and Measurement of Everyday Cognition (ECOG12). Logistic Regression Models were fitted to predict Clinical Dementia Global Ratings (CDR 0.5 vs. 0) to evaluate cognitive dispersion as an independent predictor in the whole sample, White participants and Black participants, controlled for demographics, vascular risk, and physical activity. Logistic Regression Models were also evaluated with CFI or ECOG12 as additional covariate.ResultGreater cognitive dispersion was correlated with older age, greater vascular burden and less physical activity, but not SCD. Cognitive dispersion was significantly higher in men, Black participants, and participants with less education. Cognitive dispersion predicted CDR in Black participants (OR = 4.7, p<0.01), and trended in the whole sample (OR = 1.6, p = 0.05), but was not significant in White participants (OR = 1.2, p = 0.63). Results hold when controlled for SCD (Table 1).ConclusionResults supported cognitive dispersion as a sensitive objective metric, in addition to self‐report SCD, to identify individuals showing the earliest clinical signs of decline, particularly among those underrepresented in traditional norms.
Exploring Quality of Life Rated by Caregivers and Care Recipients Among People Living With Dementia
Authors: Labovic Dubravka , Papazyan Anna , Josephson Karen , McCurry Susan M , Teng Edmond , Alessi Cathy A , Martin Jennifer L , Song Yeonsu 
Published: December 2023

AbstractBackgroundQuality of life (QOL) of people living with dementia (PLWD) does not necessarily decrease as the disease progresses and understanding multiple aspects of QOL is an integral part of dementia care. Prior evidence suggests a discrepancy between caregiver‐ and care recipient‐rated QOL of PLWD, yet factors related to this QOL are still lacking. We aimed to examine the relationship between QOL of PLWD rated by both the caregivers and care recipients and characteristics of PLWD and caregivers.MethodsWe analyzed data from 40 caregivers and 29 PLWD enrolled in a clinical trial testing a dyadic sleep intervention for PLWD and their family caregivers. Measures included QOL‐Alzheimer’s Disease (QOL‐AD), caregiver characteristics (age, education, White vs Non‐White, spouse vs non‐spouse, Center for Epidemiological Studies of Depression [CESD], Zarit Burden Interview [ZBI]), and care recipient characteristics (Revised Memory and Behavior Problems Checklist [RMBPC], Activities of Daily Living [ADLs] and Instrumental ADL [IADLs], Mini‐Mental State Examination [MMSE]). Pearson correlation analyses were conducted.ResultsMean QOL‐AD scores rated by caregivers and care recipients were 32.25 (SD 6.14) and 37.41 (SD 5.96), respectively. The scores were not significantly associated with each other. There were significant correlations between caregiver‐rated QOL‐AD scores and caregiving burden (r = ‐0.45, p = 0.004), depressive symptoms of caregivers (r = ‐0.52, p<0.001), frequency of dementia related behaviors (r = ‐0.57, p<0.001), caregivers’ distress associated with these behaviors (r = ‐0.54, p<0.001), and ADLs (r = 0.44; p = 0.004) and IADLs of PLWD (r = 0.43, p = 0.006). However, no caregiver or care recipient characteristics were associated with care recipient‐rated QOL‐AD scores.ConclusionOur findings confirm a discrepancy between caregiver‐ and care recipient‐rated QOL of PLWD. Among caregivers, higher levels of caregivers’ burden and depressive symptoms as well as lower levels of physical function and greater numbers of dementia‐related behaviors were associated with lower levels of perceived QOL‐AD, but not with the care recipient‐rated QOL. Further research should examine the possible mechanism underlying discrepancy of QOL‐AD rated by caregivers and care recipients to identify possible targets for interventions to improve QOL among PLWD.
Affordable, accessible, community‐delivered hearing care among individuals with cognitive impairment: Lessons from the HEARS RCT
Authors: Nieman Carrie L , Betz Joshua , Morales Emmanuel E. Garcia , Suen Jonathan J , Trumbo Jami , Marrone Nicole L , Han Hae‐Ra , Szanton Sarah L , Lin Frank R , Oh Esther S 
Published: December 2023

AbstractBackgroundHearing loss is highly prevalent and associated with adverse health outcomes but undertreated among individuals with cognitive impairment, particularly African Americans. The incorporation of community health worker (CHW)‐partnered models may increase access and reduce disparities.The HEARS intervention is a hearing care program delivered by CHWs that provides a low‐cost amplification device. To assess the efficacy of CHW‐delivered hearing care provided to community‐dwelling older adults, including those with cognitive impairment, a randomized clinical trial was conducted.MethodAn open label randomized clinical trial took place in 13 community sites in Baltimore, Maryland. 348 older adults were screened and 151 participants with hearing loss were randomized to receive a CHW‐delivered hearing care intervention versus 3‐month waitlist control.The primary outcome was change in communication function (Hearing Handicap Inventory for the Elderly‐Screening [HHIE‐S]) from baseline to 3‐months post‐randomization. The average treatment effect was estimated using the doubly‐robust weighted least squares estimator. This pre‐specified subgroup analysis was stratified by cognitive status using the total MoCA score (≤25: cognitive impairment; post hoc sensitivity analysis using ≤22).ResultAmong 149 randomized participants with MoCA data, 100 individuals were cognitively impaired (Mean adjusted MoCA: 21(SD 3.5); 52% African American; 70% low‐income). At 3‐months post‐intervention, 66% with cognitive impairment reported daily device use versus 76% for those without cognitive impairment. Communication function significantly improved among individuals with cognitive impairment compared with the control, with an estimated average treatment effect of ‐13.92 HHIE‐S change (95% CI:‐16.84,‐10.86), comparable to those without cognitive impairment (‐11.47; 95% CI:‐18.04,‐4.17). Post hoc sensitivity analysis using a ≤22 MoCA cut‐off for cognitive impairment yielded similar findings.ConclusionAmong individuals with cognitive impairment, a CHW‐delivered low‐cost amplification device intervention, compared with a waitlist control, significantly improved communication function. The improvements were comparable to participants without cognitive impairment and similar in magnitude to improvements documented for older adults who received conventional clinic‐based hearing care with hearing aids fit by audiologists. To the authors’ knowledge, this trial was the largest trial to date of a hearing care intervention in the U.S. of African American older adults and low‐income older adults with hearing loss and cognitive impairment.
Co‐morbidity of sensory loss (hearing, vision, olfaction) in persons with or at risk for dementia: Implications for brain structure and function
Authors: Phillips Natalie 
Published: December 2023

AbstractBackgroundHearing, vision, and olfactory loss have each independently been associated with cognitive decline and increased risk for dementia. Research has examined their individual relationships with brain structure and function, but these predictors have not been examined together in older adults who vary along a spectrum of risk for dementia. We examined groups who range from relatively low risk (those with normal cognition and no cognitive complaints (NC)), to those with higher risk, namely individuals with subjective reports of cognitive decline (SCD) but normal cognition and those with mild cognitive impairment (MCI).MethodWe used data from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS‐ND) study. Hearing loss was assessed with a pure‐tone screening protocol and a speech‐in‐noise test, vision was assessed with the MNRead for visual acuity and the MARS test for contrast sensitivity, and olfaction was assessed with the Brief Smell Identification Test (BSIT). We examined the frequency of sensory deficits in 60 NC (mean age = 69 years; mean education = 16 years), 55 participants with SCD (age = 70; education = 17), 102 with MCI (age = 72; education = 16), and 47 with Alzheimer’s disease (AD, age = 75; education = 15). Participants were matched on age and education, except for AD participants who were older.ResultsThe frequency of having at least one impairment in at least one sensory domain increased across groups (55% NC, 62% SCD, 75% MCI, 96% AD). A deficit in olfaction was the most common single deficit. Sensory deficits became increasing more co‐morbid across the risk spectrum. Hearing loss and olfaction loss were each associated with lower hippocampal volume and hearing loss was associated with alterations in functional brain connectivity in the default mode network.ConclusionThese analyses indicate that sensory loss is highly frequent and co‐morbid in persons with or at risk for dementia. These findings have implications for cognition, brain function, functional activities, and care delivery for persons with or at risk for dementia.
Impact of Single Compared to Dual Sensory Loss in People with Dementia on Care Partner Outcomes
Authors: Alexopoulos Panagiotis , Hann Mark , Leroi Iracema 
Published: December 2023

AbstractBackgroundBoth hearing and vision loss impact significantly on outcomes in people with dementia as well as their care partners. The study aimed to compare the impact on care partner outcomes of hearing loss alone and dual sensory (both hearing and vision) loss in people with dementiaMethodsThe study sample includes data from the SENSE‐Cog Trial (www.sense‐cog.eu). Care partner psychological distress was ascertained using the 12‐item General Health Questionnaire and the Hospital Anxiety and Depression Scale. Caregiving intensity was assessed using the care partner items of the RUD Lite. Dementia symptoms were assessed with the MOCA, the 12‐item Neuropsychiatric Inventory and the Bristol Activities of Daily Living scale. Vision loss was defined by the presence of binocular visual acuity of not more than 6/9.5 and greater than 6/60 in Snellen metric using the Portable Eye Examination Kit (PEEK) vision tool and visual field greater than 10° using confrontation visual field test. Hearing loss was defined by a bilateral hearing difficulty, indicated by failure of a pure tone hearing screening test in both ears. Statistical analyses included comparison between groups with different sensory losses (hearing‐ vs. dual loss) and regression analyses.ResultsData of dyads of people with dementia and either hearing loss (N = 150) or dual sensory loss (N = 92) and their care partners (female 72.5%; male 27.5%) were considered. Participants had Alzheimer’s dementia (65%), vascular dementia (16%) or mixed dementia (19%), with mean MOCA score 16.6 (range 10 – 28). 73% of patients lived with partner or family and 24% alone. Higher caregiving intensity and higher psychological distress were observed in care partners of patients with dual sensory loss compared to care partners of people with hearing loss only after controlling for the impact of cognitive deficits, neuropsychiatric symptoms, performance on activities of daily living and demographic characteristics.ConclusionsDual sensory loss in people with dementia increases care partner distress and caregiving intensity compared to single hearing loss. Shedding light on sensory loss in dementia may pave new ways towards more effective symptom management and higher quality of life of both patients and their care partners.
Production of a PSEN1 genetically engineered marmoset model of early‐onset Alzheimer’s Disease
Authors: Park Jung Eun , Carter Gregory W , Silva Afonso C , Strick Peter L , Rizzo Stacey J Sukoff , Homanics Gregg E 
Published: December 2023

AbstractBackgroundThe lack of an adequate animal model of Alzheimer’s disease (AD) that mirrors the natural onset and progression of the human disorder has been a substantial barrier to basic and translational research into AD. Consequently, many fundamental questions remain about the key mechanisms that initiate the disease and the factors that promote its progression. While rodents are valuable AD models, nonhuman primates (NHPs) offer many advantages and have greater translational relevance. The common marmoset (Callithrix jacchus) is a small, prolific New World NHP that is amenable to genetic engineering and is rapidly becoming a valuable model organism, especially for neuroscience research.MethodWe used CRISPR/Cas9 technology to generate marmosets with C410Y or A426P point mutations in the PSEN1 gene. In humans, these mutations lead to familial early‐onset autosomal dominant Alzheimer’s Disease. Briefly, we designed, synthesized, and injected CRISPR/Cas9 reagents into single‐cell embryos that were subsequently transferred to synchronized recipient females. One adult C410Y founder animal was bred to a wild‐type mate.ResultTo date, we have produced seven live‐born marmosets harboring the PSEN1 C410Y (3 males, 1 female) or A426P (1 male, 2 females) mutations. One male founder animal, a compound heterozygote harboring C410Y and 1bp insertion PSEN1 alleles, has successfully sired three litters and transmitted the C410Y substitution (n = 6) and the 1bp insertion (n = 5) alleles to F1 offspring. We are currently characterizing the founders and F1 offspring using fluid‐based biomarkers, non‐invasive neuroimaging, and behavioral assessment to identify early markers of disease progression.ConclusionCRISPR/Cas9 gene editing was used to successfully establish a line of genetically engineered marmosets expected to model early‐onset AD. This nonhuman primate model will bridge the rodent‐to‐human translational gap and enable detailed studies of the early‐life molecular determinants of AD pathogenesis.