bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationships between well‐being and cognitive function among Native American, Black, and White participants in the Wisconsin Alzheimer's Disease Research Center
Authors: Wyman Mary F , Umucu Emre , Livingston Sydnee , Lambrou Nickolas H , Carter Fabu P , Van Hulle Carol A , Johnson Sterling C , Asthana Sanjay , Gleason Carey E , Zuelsdorff Megan 
Published: December 2021

AbstractBackgroundHigh subjective well‐being is a hallmark of successful aging, and growing evidence demonstrates its associations with better cognitive function and slowed decline in aging adults. To date, predominantly white study cohorts preclude an understanding of well‐being as a protective factor in minoritized populations. Using validated NIH Toolbox Emotion Battery measures, we examined associations between three facets of psychological well‐being and cognitive test performance in a cognitively healthy cohort of Black, American Indian/Alaska Native (AI/AN), and white older adults enrolled in the Wisconsin Alzheimer’s Disease Research Center’s (ADRC) Clinical Core.MethodsParticipants with normal cognition and with complete Emotion Battery data for at least one visit were included in the analytic sample. Key well‐being predictors included t‐scores of self‐reported positive affect, general life satisfaction, and life meaning and purpose surveys. Outcomes of interest were performance on tests of processing speed and flexibility (Trails A and B completion time) and episodic memory (Rey Auditory and Verbal Learning Test, Trials 1‐5 & Delayed). The sample was stratified by race before cross‐sectional multivariable regression models were used to model demographic‐adjusted predictor‐outcome relationships.ResultsIn the combined, predominantly female sample, average age was 63.8 (SD=8.3). AI/AN participants (N=25) were older, and Black (N=91) and AI/AN reported fewer years of formal education than their white peers (N=433; Table 1). No racial disparities were observed in positive affect or life purpose scores, but Black and AI/AN participants reported lower life satisfaction. Consistent relationships between life satisfaction and processing speed were observed: across all racial groups, higher t‐scores associated with faster completion time, though estimate precision was limited by small sample sizes (Table 2 and Figure 1).ConclusionsThese ADRC data reaffirm racial disparities in life satisfaction observed elsewhere, which is notable in light of the robust associations of life satisfaction with key components of executive function. Identifying modifiable sources of cognitive resilience and protection against age‐related change is crucial for addressing the dementia crisis and its burden on Black and Native communities. Our findings point to next steps including triangulation with AD biomarkers and exploring population‐specific upstream determinants of life satisfaction that can inform intervention efforts focused on well‐being.
Blood neurofilament light, Parkinson’s disease, Parkinsonism, and physical function in a longitudinal population study
Authors: Halloway Shannon , Desai Pankaja , Aggarwal Neelum T , Agarwal Puja , Evans Denis A , Rajan Kumar B 
Published: December 2021

AbstractBackgroundBlood biomarkers of parkinsonism and Parkinson’s disease (PD) may allow for earlier identification of these conditions and improved longitudinal investigation of PD pathogenesis. Neurofilament light (Nf‐L), a neuronal cytoplasmic protein, is a biomarker of neurodegeneration measurable in CSF or blood. We examined the longitudinal association of serum Nf‐L with clinically diagnosed PD, parkinsonian signs, and physical functioning change over 16 years in a population‐based sample of Black and White older adults.MethodsData came from 1,327 older participants from the Chicago Health and Aging Project (CHAP), a longitudinal population‐based study of common chronic conditions of aging. Clinical evaluations included assessing parkinsonian signs in four domains, bradykinesia, parkinsonian gait, rigidity, and tremors using a structured version of the United Parkinson’s Disease Rating Scale. PD was diagnosed by board certified neurologists. Parkinsonian signs were reported as the four domain scores and a global parkinsonian score (combination of domain scores). Physical function was assessed by performance‐based tests. Serum Nf‐L was measured with an ultrasensitive immunoassay.ResultsAfter adjusting for demographic characteristics, the APOE‐e4 allele, and cognitive function, a 2‐fold higher concentration of serum Nf‐L was associated with the development of clinical PD (OR = 2.54, 95% CI: 1.70, 3.81), and global parkinsonian scores (OR = 2.44, 95% CI: 1.94, 2.94). This association was significant over five years before diagnosis. Compared to participants below 18.5 pg/mL of serum Nf‐L at baseline, participants in between 18.5–25.4 pg/mL, 25.4–37.3 pg/mL, and above 37.3 pg/mL had a higher odds ratio of clinical PD at all time intervals ranging from the time of diagnosis to greater than five years before diagnosis. A higher concentration of serum Nf‐L was associated with a faster decline in physical functioning over the duration of the study. In participants with 2‐fold higher concentrations of serum Nf‐L, the annual rate of decline in physical functioning increased by 0.15 units (95% CI: 0.21, 0.08).ConclusionsSerum Nf‐L predicted the development of clinically diagnosed PD, parkinsonian signs, and physical functioning decline in a population‐based sample. Our findings suggest that Nf‐L may serve as a potential biomarker for physical functioning outcomes in older adults.
White matter microstructure and cognitive functioning across healthy older adults with different APOE alleles
Authors: Lacey Colleen , Gawryluk Jodie 
Published: December 2021

AbstractBackgroundAPOE alleles play an important neurobiological role in the development of Alzheimer’s Disease (AD), including modifying structure of white matter in the brain and cognitive decline (Gold et al., 2012; Reas et al., 2019). However, certain alleles (i.e., APOE‐e4) have be studied more than others (i.e., APOE‐e2 & e3), and have been primarily studied in individuals already diagnosed with AD, rather than in healthy older adults. While APOE‐e4 is well establish risk factor for AD, APOE‐e2 may play a role in protective mechanisms against AD, and APOE‐e3 may be neutral, yet their underlying neural mechanisms and association with cognitive functioning in the healthy aging brain are equivocal (Suri et al., 2013). Thus, the current study aimed to investigate the influence of different APOE alleles on white matter microstructure and cognition in healthy older adults.MethodWhite matter microstructure, memory, and executive functioning (EF) were compared between cognitively normal older adults with either APOE‐e2+ (n= 16, mean age= 76), APOE e3e3 (n= 64, mean age= 74), or APOE‐e4+ (n=35, mean age=73). White matter microstructure was compared using Diffusion Tensor Imaging (DTI) Track‐based spatial statistics (TBSS) methods to derive fractional anisotropy (FA). Whole‐brain mean FA was compared first between e3e3 and e2+ and then between e3e3 and e4+ groups. Memory and executive functioning composite scores were compared, including covariates of age, sex, and education levels, using multivariate analysis of covariance (MANCOVA). All data were retrieved from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).ResultNo significant differences in white matter microstructure (FA; p> 0.05, corrected) were observed. Further, groups were not significantly different in memory, EF, age, sex, or education levels (p=0.59).ConclusionThese results indicate that white matter microstructure, memory, and EF changes are not evident in the healthy brain as a function of APOE allele presence. DTI may not be sensitive to APOE‐related changes in the healthy brain; nonetheless, future investigations should evaluate whether other structural (e.g., grey matter volume) and functional (e.g., fMRI) differences are evident across different APOE alleles in this population, as well as examine other cognitive domains.
UW Project ECHO‐Dementia: Implementation of a virtual clinic and telementoring program to improve dementia diagnosis and treatment in rural and under‐resourced primary care settings
Authors: Rhoads Kristoffer , Isenberg Nancy , Schrier Allyson 
Published: December 2021

AbstractBackgroundPrimary care providers are on the front lines of dementia care and frequently the first point of contact for individuals and families concerned about changes in memory and thinking. In addition to the challenges of managing complex medical comorbidities, primary care providers in rural or lower‐resource settings often lack access to specialists, interdisciplinary teams or other programs and services to aid in diagnosis and care of individuals with mild cognitive impairment and dementia. The current project extends an existing technology‐based hub and spoke model virtual clinic, Project ECHO (Extension for Community Healthcare Outcomes, University of New Mexico), to improve diagnosis and care of dementia in primary care.MethodThe current project is an extension of work related to the Washington State Plan for Alzheimer's Disease and Other Dementias with implementation supported by legislative funding. The program includes an interdisciplinary expert panel (“hub”) meeting with participants (“spokes”) including primary and allied health care providers from healthcare systems, group practices, and solo practitioners. The twice‐monthly virtual clinic sessions include a brief didactic followed by case‐based learning in an “all‐teach, all‐learn” format emphasizing expertise and experience of spoke sites as well as the hub. Participants are provided with resources discussed during the clinic session, ongoing opportunities for consultation, and free continuing education credits.ResultsLaunching amid the COVID‐19 pandemic, the program has provided over 250 hours of education to more than 50 providers across 20 unique sites. Post session surveys indicate that the program is well‐received with 2 in 3 providers indicating that they will change their practice based on learning. Surveys also demonstrate significant increases in both knowledge and confidence in dementia‐specific diagnosis and care.ConclusionThe success of the current project demonstrates both the feasibility and benefit of leveraging technology to deliver dementia‐related education to primary care providers in rural and under‐resourced settings. While initially hampered by disruptions in care due to the COVID‐19 pandemic, increased technological proficiency on the provider and systems level has appeared to be a benefit in terms of resources and comfort participating in a virtual education program to scale Dementia Capable Care in Primary Care.
Association of the Mediterranean diet with cognition in a Western population
Authors: Sabeti Neda , O'Leary Fiona , Flood Victoria M , Valenzuela Michael , Radd‐Vagenas Sue , Noble Yian , Rangel Carolina Almendrales , Gracham Ali , Heffernan Megan , Sachdev Perminder S , Brodaty Henry , Lautenschlager Nicola T , Singh Maria A Fiatarone 
Published: December 2021

AbstractBackgroundThe Mediterranean‐style diet (MD) is promoted as one of the healthiest dietary patterns and has been shown to reduce cognitive decline in some randomised controlled trials (RCTs). This pattern is plant‐based with a focus on vegetables, legumes, fish, and olive oil, with low intake of red meats and foods high in sugar and saturated fats. The Maintain Your Brain (MYB) study is an online multi‐domain RCT targeting modifiable risk factors for dementia, including diet. This study investigated cross‐sectional associations between adherence to a MD pattern and cognition.MethodsParticipants enrolled in MYB were recruited from the Sax Institute’s larger 45 and Up Study, and included those with all baseline MYB assessments (n=6236). Diet was assessed using the validated Mediterranean Diet and Culinary Index tool. This 50‐item tool assesses intake of nine desirable and four undesirable features of the MD diet and allows derivation of the Mediterranean Diet Adherence Screener (MEDAS). Computerised cognitive tests, administered through the MYB digital platform, were used to assess domains of executive function, complex attention, learning and memory and global cognition.ResultsParticipants were 46% male, with mean (SD) age 65.0 (5.8) years, BMI 26.6 (4.9) kg/m2 and well educated (46% with tertiary education). Higher MEDAS scores were associated with being female, younger, better educated and having a lower BMI (all p<0.001). Overall participant adherence to a MD pattern was low; MEDAS score 6.1 (2.1)/14. After covariate adjustment and correction for multiple analyses in hierarchical linear regression models, better MEDAS scores were significantly associated with worse (lower) z‐scores for executive function (β ‐0.018, p=0.003). For every 1‐point higher MEDAS score, executive function z‐scores were 0.018 lower. This unexpected negative association was clinically very small. There were no significant associations with other cognitive domains.ConclusionAdherence to a MD was sub‐optimal in this well‐educated Australian sample. The one unexpected finding is likely not clinically meaningful given its size. Additionally, as this was a cross‐sectional study, reverse causality cannot be ruled out. Results from the main MYB RCT will provide data on MD acceptance and impact in a Western dietary environment.
Cultural adaptation and validation of the Addenbrooke’s Cognitive Examination III in a Taiwanese population (T‐ACE‐III) presenting to hospital with suspected dementia
Authors: Yu Ruan‐Ching , Mukadam Naaheed , Kapur Narinder , Stott Joshua , Livingston Gill 
Published: December 2021

AbstractBackgroundThe Addenbrooke’s Cognitive Examination III (ACE‐III) is an effective cognitive test for detecting dementia in many countries and covers a wide range of cognitive domains. However, there has been no study about the usefulness of the ACE‐III in patients with suspected dementia in Taiwan where patients use Traditional Chinese, unlike mainland China. We therefore aimed to culturally adapt and find the sensitivity and specificity of the ACE‐III for investigating people with possible dementia presenting to hospital in Taiwan.MethodWe used the guideline for cross‐cultural adaptation process to culturally adapt the simplified Chinese version (C‐ACE‐III) for Taiwanese populations (T‐ACE‐III). We recruited consenting patients who had presented to clinics with suspected dementia in Northern Taiwan and had been through the diagnostic process. We timed the interviews and conducted receiver operating characteristic (ROC) curve analysis to test the ability of the T‐ACE‐III to differentiate between dementia and non‐dementia using clinical diagnosis as the gold standard. We used linear regression to find significant predictors of ACE‐T score entering age, education, sex, language group, and dementia status as possible predictors.Result110 participants were invited, of whom 91 Chinese/ Hokkien‐speaking individuals aged 49 to 93 years consented to take part and ninety completed the test: 24 males and 33 females with dementia and 12 males and 21 females without. It took on average 16.3 and 24.0 minutes to administer in non‐dementia and dementia group, respectively. The T‐ACE‐III demonstrated a sensitivity of 100.0% and a specificity of 78.8%, for distinguishing dementia from non‐dementia with a cut‐off value of 86/87, a sensitivity of 89.5% and a specificity of 100.0%, with a cut‐off value of 73/74. The area under the curve (AUC) = 0.99 in T‐ACE‐III. The diagnosis of dementia, and language used were significant predictors accounting for 68.1% of the variance in T‐ACE‐III scores.ConclusionThe culturally adapted T‐ACE‐III is a brief, reliable, and acceptable tool for discriminating dementia from non‐dementia cases in a Taiwanese population in a memory clinic setting.
Differential associations of modifiable and non‐modifiable dementia risk factors with memory decline and hippocampal volume loss in Aβ‐ and Aβ+ cognitively normal older adults
Authors: Rosenich Emily , Pase Matthew P , Yassi Nawaf , Fripp Jurgen , Laws Simon M , Fowler Christopher J , Rowe Christopher C , Masters Colin L , Maruff Paul T , Lim Yen Ying , Group AIBL Research 
Published: December 2021

AbstractBackgroundThe extent to which modifiable and non‐modifiable risk factors contribute to cognitive decline in older people remains unclear. We sought to determine the association of modifiable and non‐modifiable components included in the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score with memory decline and brain volume loss in cognitively normal (CN) older adults, taking Aβ status into account.MethodAIBL study participants (age range: 60‐90) who completed ≥2 neuropsychological assessments and an Aβ PET scan (N=626) were included in this study. We computed the standard CAIDE (age, sex, APOE ε4 status, education, hypertension, body mass index, hypercholesterinemia, physical inactivity), and a modifiable CAIDE (modCAIDE; education, modifiable vascular risk factors) for each participant. Aβ+ was classified using a Centiloid ≥25. Linear mixed models assessed interactions between each CAIDE score on episodic memory (EM) and hippocampal volume (HV) over time in Aβ‐ and Aβ+ CNs. Non‐modifiable variables from the standard CAIDE (age, sex, ε4) were included as separate predictors in all modCAIDE models to assess differential associations.ResultWe observed a significant standard CAIDE x time interaction on EM decline in Aβ+ (β=‐0.08(0.04); p=0.02) and Aβ‐ participants (β=‐4.07(1.13); p<0.001), and a significant standard CAIDE x time interaction on HV loss in Aβ+ participants only (β=‐0.06(0.02); p=0.003). When modifiable and non‐modifiable CAIDE components were considered separately, we observed a significant ε4 x time interaction only for EM decline (β=‐0.32(0.07); p<0.001) and HV loss (β=‐0.13(0.04); p<0.001) in Aβ+ participants, but no significant modCAIDE x time interaction (both p’s>0.29). In Aβ‐ participants, we observed a significant modCAIDE x time interaction on memory decline (β=‐0.04(0.02); p=0.02), but no significant ε4 x time interaction (β=‐0.07(0.04); p=0.11). No significant ε4 x time or modCAIDE x time interactions were observed for HV loss in Aβ‐ participants.ConclusionOur results are consistent with previous studies showing that ε4 is associated with an increased rate of EM decline and HV loss in Aβ+ CNs. In Aβ‐ CNs, lower prevalence of modifiable cardiovascular risk factors was associated with better EM performance over time, suggesting interventions to reduce modifiable risk factors could be beneficial in this group.
API generation program: Active immunotherapy CAD106 slows amyloid deposition in cognitively unimpaired APOE4 homozygotes
Authors: Riviere Marie‐Emmanuelle , Turner Raymond Scott , Sui Yihan , Laurent Nathalie , Langbaum Jessica B. , Cazorla Pilar , Ricart Javier , Seneca Nicholas , Caputo Angelika , Reiman Eric M. , Tariot Pierre N. , Graf Ana 
Published: December 2021

AbstractBackgroundThe Alzheimer’s Prevention Initiative (API) Generation Study 1 (NCT0256551) evaluated CAD106, an active immunotherapy against Aβ, in delaying the clinical onset of Alzheimer’s disease in a cohort of cognitively unimpaired APOE4 homozygotes. Effect of CAD106 on brain amyloid burden after 2 years was measured by amyloid PET. Previous studies in mild AD showed that doses up to 450μg CAD106 induced sustained Aβ‐antibody response with no major safety concerns (Vandenberghe, 2017).MethodCognitively unimpaired APOE4 homozygotes age 60‐75 were enrolled using a 5:3 randomization ratio (CAD106 450μg:placebo). Intramuscular injections were administered at 0, 6, 12 weeks and then quarterly with alum as adjuvant. PET scans were conducted at baseline and 2 years mainly with florbetapir. Standard uptake value ratios (SUVRs) were calculated using cortical composite region in reference to cerebellum and converted to centiloids.ResultOut of 65 randomized participants (42:23 CAD106:placebo) 59 were followed for 18 months or longer. Mean age at baseline was 65 years, 68% were female. Mean baseline RBANS total score was 106. Year 2 PET scans were acquired in 35 CAD106 and 16 placebo participants with centiloid mean baseline of 49.5 (38.7).CAD106 induced measurable Aβ‐specific IgG titers in all treated participants. Mean (SD) annualized centiloid change from baseline was +8.4 (6.7) on placebo without change with CAD106 ((‐0.9 (5.7), p<0.0001). The effect was more pronounced in amyloid positives: +9.4 (7.7) on placebo and ‐1.8 (6.0) with CAD106, vs in amyloid negatives: +6.7 (4.7) on placebo and +2.2 (2.8) with CAD106. In the CAD106 arm, the effect on PET correlated with antibody titers, especially for amyloid positive subgroup.Higher incidences for psychiatric (21% vs 13%) and general disorders / injection site (64% vs 22%) adverse events were reported with CAD106 vs placebo. Three cases of ARIA (2 ARIA‐H and 1 ARIA‐E) occurred on CAD106 (none on placebo). Cognition scores remained stable for 18 months in both groups.ConclusionCAD106 is the first active immunotherapy shown to slow amyloid deposition in humans. Treatment with CAD106 might have a positive risk/benefit profile for prevention of amyloid deposition in high‐risk populations.
The cerebrospinal fluid interleukin 8 (IL‐8) concentration in Alzheimer’s disease (AD)
Authors: Doroszkiewicz Julia , Kulczynska‐Przybik Agnieszka , Dulewicz Maciej , Borawska Renata , Krawiec Anita , Slowik Agnieszka , Mroczko Barbara 
Published: December 2021

AbstractBackgroundAlzheimer disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. The hallmarks underlying AD pathology are amyloid‐β peptides, phosphorylated tau proteins and neuroinflammation. In vitro studies on cultured human microglia display a significant role of Interleukin 8 in neuroinflammation. Furthermore, CXCR2, IL‐8 receptor, was found in dystrophic neurites which suggests connection to neuroinflammation in AD. Literature data indicates that gene polymorphism in IL‐8 may affect the predisposition of Alzheimer's disease. It has been observed that IL‐8 may increase Tau phosphorylation and subsequent NFTs formation. Thus, the aim of our research was to measure the concentration of IL‐8 in cerebrospinal fluid of AD patients and non‐demented controls. Moreover, we compare them to the concentrations of classical AD biomarkers, such as Aβ‐42, Aβ‐42/Aβ‐40, Tau and pTau181.MethodThe concentrations of IL‐8 and classical AD biomarkers, such as Aβ‐42, Aβ‐42/Aβ‐40, Tau and pTau181 were measured in cerebrospinal fluid (CSF) of 15 AD patients and 16 non‐demented controls using immunoenzyme assays.ResultIL‐8 concentrations were significantly higher in AD patients in comparison to non‐demented controls. Moreover, increased CSF levels of IL‐8 correlated with Aβ‐42/Aβ‐40 ratio, MMSE, Tau and pTau181 in the whole study group.ConclusionFindings of our research suggest a potential role of IL‐8 in pathology of AD. However, follow‐up studies on larger study group are needed. Acknowledgement: The study was conducted with the use of equipment purchased by Medical University of Białystok as part of the RPOWP 2007‐2013 funding, Priority I, Axis 1.1, contract No. UDA‐RPPD.01.01.00‐20‐001/15‐00 dated 26.06.2015.