bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capturing cognitive health disparities on the national and state level using 2023 proposed federal racial and ethnic categories: the case for a Middle Eastern and North African checkbox
Authors: Kindratt Tiffany B , Smith Alexandra 
Published: January 2025

AbstractBackgroundMost research on cognitive difficulties in the US focus on minoritized groups that are part of the federal minimum reporting guidelines, include White, Black, Hispanic/Latino, Asian, American Indian/Alaskan Native (AI/AN), and Native Hawaiian/Other Pacific Islander (NH/OPI) individuals. Research has begun to describe cognitive difficulties among Middle Eastern and North African (MENA) adults, but it is limited because they are defined as White. In 2023, the Office of Management and Budget (OMB) proposed adding a separate checkbox for MENA individuals. Our objective was to estimate and compare the odds of cognitive difficulties among MENA adults compared to White, Black, Hispanic/Latino, Asian, AI/AN, NH/OPI adults in the US and four states (California, New York, Michigan, and Texas) after adjusting for sociodemographic characteristics.MethodWe analyzed data from the 2017‐2021 American Community Survey (ages≥45 years; n = 7,284,988). Cognitive difficulties (yes/no) among adults (ages 45+ years) who self‐identified their race/ethnicity from one of the six minimum reporting categories (White, Black, Hispanic/Latino, AI/AN, NH/OPI) were compared to those who reported a MENA ancestry/birthplace.ResultMENA adults in the US had greater odds of reporting cognitive difficulties compared to White, Black, Hispanic, Asian and AI/AN adults, but there was no difference when compared to NH/OPI adults after adjusting for covariates. In California, MENA adults had higher odds of cognitive difficulties compared to White, Black, Hispanic/Latino, Asian, and NH/OPI adults. In New York, MENA adults had higher odds of cognitive difficulties compared to Asian adults. MENA adults in New York had lower odds of cognitive difficulties when compared to Black, Hispanic/Latino, and AI/AN adults. In Michigan, MENA adults had lower odds of cognitive difficulties than Black, but higher odds than Hispanic/Latino and Asian adults. In Texas, MENA adults had higher cognitive difficulties compared to White, Hispanic/Latino, and Asian adults.ConclusionThis study expands on previous research uncovering cognitive difficulties among Arab Americans using the 2023 OMB proposal to include MENA as a checkbox as part of the minimum reporting standards for race/ethnicity in the US. It also provides the first state‐based estimates of cognitive difficulties among MENA adults living in California, New York, Michigan, and Texas.
Insulin resistance’s role in mediating physical activity’s impact on beta amyloid accumulation and tau phosphorylation: A scoping review
Authors: Slee Michael G , Scotney Joanne , Rainey‐Smith Stephanie R , Erickson Kirk I. , Sohrabi Hamid R. , Brown Belinda M. 
Published: January 2025

AbstractBackgroundType 2 diabetes (T2D) and Alzheimer’s disease (AD) are amongst the top 10 leading causes of death worldwide. T2D is associated with increased AD risk and brain beta amyloid (Aβ) burden, suggesting underlying mechanistic relationship between AD and T2D. Insulin signalling pathways, which can regulate the accumulation of Aβ and phosphorylation of tau in the brain, is a possible underlying mechanism of the T2D‐AD relationship. Insulin resistance, reduced responsiveness to insulin and T2D hallmark, has been found to impair insulin signalling pathway function. Animal studies show exercise reduces brain levels of Aβ. Whilst empirical evidence from human studies linking exercise to brain Aβ is somewhat limited, some studies have reported physical activity is associated with lower brain Aβ. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and AD biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective of this review was to identify what evidence exists that examines the association between insulin, physical activity, and Aβ/tau in animals and human studies. Particularly, what is known about the potential mediating role insulin resistance has on the physical activity ‐ Aβ/tau relationship.MethodA systematic search was performed in Cochrane library, PsycINFO, PubMed and World of Science to identify suitable publications. The search identified 343 articles with 21 articles meeting the full inclusion criteria.ResultMost animal studies showed that exercise could simultaneously reduce insulin resistance and AD pathology. Limited human studies were identified and only a few found both reduced insulin resistance and Aβ/tau associated with higher physical activity. One study provided evidence that insulin resistance may mediate the physical activity ‐ Aβ relationship, however this was not derived through standard mediation analysis.ConclusionExercise can simultaneously impact insulin resistance and AD pathology in animal models, suggesting similar underlying mechanisms. Results in human models are limited however, and no robust evaluation of insulin resistance’s mediating role in the physical activity ‐ Aβ/tau relationship exists. Future focus on mediation impact should be investigated to enhance our understanding of physical activity’s role in reducing AD risk.
Dementia risk reduction assessed with ANU‐ADRI in the Maintain Your Brain trial, an online multidomain intervention to prevent cognitive decline and dementia
Authors: Chau Tiffany , Briggs Nancy , Popovic Gordana , Anstey Kaarin J. , Heffernan Megan , Singh Maria A. Fiatarone , Valenzuela Michael , Millard Michael , Sachdev Perminder S. , Lautenschlager Nicola T , Jorm Louisa , Ginige Jeewani Anupama , Brodaty Henry 
Published: January 2025

AbstractBackgroundThe Maintain Your Brain (MYB) randomised controlled trial (RCT) aimed to prevent cognitive decline and dementia through a multidomain risk‐reduction intervention delivered digitally. The intervention targeted four modifiable risk areas (physical inactivity, poor diet, cognitive inactivity, and depression and/or anxiety). MYB ran for three years and targeted older Australians aged 55‐77 years. We previously reported significant benefits on cognition in the intervention group compared to the control group. Here we report the outcome on a validated dementia risk assessment tool.MethodThe self‐reported short form of the Australian National University Alzheimer’s Disease Risk Index (ANU‐ADRI‐SF; 1) was used to assess dementia risk in MYB. To examine risk and protective factors, non‐modifiable factors (age and sex) were removed. Unrealistic values were also removed as part of the data cleaning process. A generalised linear mixed model with appropriate response distributions and link function was run to examine the group (intervention vs control) by time (baseline, 12‐, 24‐, and 36‐months) interaction. An additional analysis adjusted for baseline age, gender, and years of education was run.ResultOf 14,064 participants who consented, 6,104 participants were eligible and completed baseline assessments. They were randomised 1:1 to the intervention (n = 3,051) or control (n = 3,053) group. Upon removing outliers (n = 58), 6,046 participants were included in the mixed model analysis. Analysis revealed significant intervention effects on dementia risk change over three years (0.56, 95%CI ‐0.88‐ ‐0.30, p<0.001). Results were replicated in the adjusted model (p<0.001).ConclusionAn online intervention program confirmed results from a 24‐month follow‐up of in‐person multicomponent interventions (2,3) in lowering dementia risk. Overall, MYB has the potential to provide a realistic path towards scalable community‐based prevention of dementia, resulting in an improvement in public health and potential economic implications.References:1. Kim S et al, Alzheimers Dement: Translational Res & Clin Interventions 2016;2:93‐982. Barbera et al., Alzheimers Dement J Alzheimers Assoc. 2020; 16:S103. Deckers K et al. Alzheimers Dement. 2021;17:1205‐1212.
Associations between glucose metabolism measures and amyloid and tau load on PET 14 years later: Findings from the Framingham Heart Study
Authors: van Gils Veerle , Tao Qiushan , Ang Ting Fang Alvin , Young Christina B. , Mormino Elizabeth , Qiu Wei Qiao , Visser Pieter Jelle , Au Rhoda , Jansen Willemijn J. , Vos Stephanie J. B. 
Published: January 2025

AbstractBackgroundType 2 diabetes and glucose metabolism have previously been linked to cognitive decline and higher risk of developing Alzheimer’s disease (AD) dementia. Yet, the relation of glucose metabolism with amyloid and tau pathology remains unclear. This knowledge will help understanding the importance of glucose regulation in relation to AD. Therefore, we aimed to investigate whether earlier age glucose metabolism measures are associated with later age amyloid and tau measures on PET.MethodWe included 288 participants (mean age= 43.1, SD=10.7, range 20‐70 years) without dementia from the Framingham Heart Study (FHS), who had data available on glucose metabolism measures, i.e. continuous plasma glucose, elevated plasma glucose (>100mg/dl), plasma insulin, and homeostatic model assessment for insulin resistance (HOMA‐IR), and a PET measure of global amyloid and/or temporal tau 14 years later (range 11‐17 years). We performed linear regression analyses to test associations of each glucose metabolism measure with amyloid or tau uptake on PET, adjusted for age, sex, and exact years of time interval. For significant findings, we explored whether age, sex, ApoE‐ε4 allele carriership or amyloid load modified the associations.ResultDemographics are shown in Table 1. Our findings indicated that elevated plasma glucose was associated with greater tau load in the brain 14 years later (B [95%CI] = 0.03 [0.01 – 0.05], p = 0.006). Findings were independent from age, sex, and amyloid load. The association was only observed in ApoE‐ε4 non‐carriers (B [95%CI] = ‐0.08 [‐0.12 – ‐0.03], p=0.001, Figure 1). Higher plasma insulin and HOMA‐IR were associated with decreased amyloid load after 14 years (B [95%CI] = ‐0.01 [‐0.02 – ‐0.00], p = 0.035 and B [95%CI] = ‐0.01 [‐0.02 – ‐0.00], p = 0.034, respectively), but this association attenuated after false discovery rate (FDR) correction (both p=0.07) and adjustment for ApoE‐ε4 carriership (insulin p=0.057 and HOMA‐IR p=0.053). No other associations were found (Table 2).ConclusionOur findings suggest that impaired glucose metabolism is associated with increased tau pathology later in life, independent from amyloid pathways. These findings suggest that glucose metabolism regulation is important to prevent neuropathology later in life.
Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer’s disease
Authors: Collij Lyduine E. , Mastenbroek Sophie E. , Mattsson‐Carlgren Niklas , Strandberg Olof , Smith Ruben , Palmqvist Sebastian , Ossenkoppele Rik , Hansson Oskar ,   the Alzheimer's Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundIdentification of concomitant Lewy Body (LB) pathology might be important for the diagnostic and prognostic work‐up of Alzheimer’s disease (AD) in clinical practice and trials. Here, we aimed to determine whether the presence of LB pathology exacerbates AD‐related disease progression.MethodsCognitively impaired (Mild Cognitive Impairment [MCI] and dementia, n=795) individuals from the ADNI cohort with available CSF α‐synuclein amplification assay (SAA) and CSF p‐tau181/Aβ42 measures were included. Linear mixed models (LMMs) with random slope and intercept were run to assess group effects on longitudinal cognition and cortical metabolism using FDG‐PET, corrected for age, sex, and baseline cognitive state, and education in case of cognition models. To investigate potential non‐linear changes in cognitive functioning, LMMs additionally included an interaction between AD/LB group and time squared (time2). Differences between AD/LB groups (n=61) in pathological scores were assessed using ordinal logistic regression models, corrected for sex, age at death, measurement interval and post‐mortem interval.ResultsParticipants were on average 75 years of age (SD=7.89), 40.8% were female, and 184 (23.1%) had no biomarker evidence of AD/LB pathology, 39 (4.9%) had isolated LB pathology (AD‐LB+), 395 (49.7%) had only AD pathology (AD+LB‐), and 177 (22.3%) had both pathologies (AD+LB+, Table 1/Figure 1). At baseline, the AD+LB+ group showed worst performance for most cognitive outcomes compared to the other groups, including the AD+LB‐ group (MMSE: p=0.008; PACC: p<0.0001). Over time, both the AD+LB‐ and AD+LB+ groups deteriorated faster in global cognitive function compared to the AD‐ groups. Importantly, this decline was more pronounced for the AD+LB+ group when compared to the AD+LB‐ group (MMSE: βAD/LB group*time2=‐0.15, p=0.005, PACC: βAD/LB group*time2=‐0.026, p=0.0015, Table 2/Figure 2). Furthermore, the AD+LB+ group showed more cortical hypometabolism at baseline and over time compared to the AD+LB‐ group, particularly in posterior brain regions (Figure 3). Neuropathological examination showed that the α‐syn SAA had 96.3% (26/27) sensitivity and 96.4% (27/28) specificity (Figure 1).ConclusionIn a cognitively impaired AD population, co‐existing LB‐positivity exacerbates cognitive decline and cortical brain hypometabolism. In vivo detection of LB pathology could improve the prognostic work‐up of AD in clinical practice and might have implications for the design of clinical AD trials.
Assessing Alzheimer’s Disease Knowledge Among Caregivers Using the Alzheimer’s Disease Knowledge Scale
Authors: Guillén Núria , Sarto Jordi , Esteller Diana , Val‐Guardiola Andrea , Fernandez‐Villullas Guadalupe , Alberique Ainoa , Piñol‐Ripoll Gerard , Balasa Mircea , Sánchez‐Valle Raquel , Martínez Neus Falgàs , Lladó Albert 
Published: January 2025

AbstractBackgroundAlthough Alzheimer’s disease (AD) is a common cause of dementia, whether patients and caregivers have notions of its risk factors, behavioral aspects or care considerations is unclear. Therefore, our study aims to evaluate caregiver’s knowledge of AD by using the Alzheimer’s Disease Knowledge Scale (ADKS).MethodThe ADKS is a comprehensive 25‐item true/false assessment tool that explores the understanding of AD. Comprising four subscales (Causes and characteristics, Communication and behavior, Considerations of care, and Risk factors and health promotion), it provides a nuanced evaluation of knowledge levels.In this prospective consecutive observational study conducted between February 2021 and December 2023, we recruited 132 participants with clinically diagnosed MCI/dementia. Their caregivers completed the Spanish version of the ADKS. Scores for the entire test, its subscales, and the individual questions were normalized on a scale from 0 to 10, to facilitate result interpretation.ResultThe mean ADKS test score was 21.7 [SD 0.7], equivalent to 4.3/10 [SD 1.4]. Most of the subscales scored below 5, indicating a poor familiarity with aspects related to “Risk factors and health promotion” (4.3/10 [SD 1.8]), “Causes and characteristics” (4.2/10 [SD 1.9]), and “Communication and behavior” (2.0/10 [SD 1.6]) (Table 1). The only subscale with an average score over 5 was “Considerations of care,” (6.7/10 [SD 2.3]).ConclusionThe findings underscore the limited knowledge of AD‐related aspects among caregivers of individuals suffering from cognitive impairment. It highlights the need to implement educational interventions in both the general population and diagnosed patients and their support networks.
EEG Cortical Sources Abnormalities During Transition Between Wakefulness and Light Sleep in Patients with Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Salamone Enrico Michele , Carpi Matteo , Jakhar Dharmendra , Lopez Susanna , Noce Giuseppe , Lizio Roberta , Percio Claudio Del , Babiloni Claudio 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) and Sleep disturbances are closely linked in a bidirectional relationship. Indeed, sleep alterations represent a precipitating factor in early pathogenesis of neurodegeneration. Conversely, the accumulation of Aβ and tau proteins directly disrupts sleep‐wake cycles. Sleep disturbances are extremely prevalent in AD and the relationship between these disorders has been thoroughly investigated. Our study is the first to investigate the electroencephalographic cortical sources during the transitional stages between quiet wakefulness and light sleep in AD patients with MCI.MethodsWe analysed data from an international database (www.pdwaves.org) comprising clinical, neuropsychological, EEG morning recordings (45 minutes), cerebrospinal fluid (CSF), structural and functional MRI data in n=36 ADMCI, n=20 showing transition to light sleep (t‐ADMCI) and n=16 without transition to sleep (nt‐ADMCI)(Table 1). The database also included clinical, neuropsychological, and EEG data of n=11 matched healthy elderly (Nold) persons transitioning to light sleep. The EEG traces were reviewed by researchers blinded to the diagnosis, divided in 4” epochs and categorised in four different vigilance conditions: Eyes Open, Wakefulness, Flattening of alpha (drowinsess), Ripples (light sleep), according to the sleep classification by Hori et al (1994). Individual alpha frequency (IAF) was used to determine the EEG delta, theta, and alpha bands. Regional EEG cortical sources were estimated using the eLORETA freeware.ResultsCompared to Nold subjects, the ADMCI subjects showed greater Frontal Delta Cortical source activity in all vigilance conditions (p<0,001) (Figure 1). Furthermore, when compared to nt‐ADMCI, t‐ADMCI showed an increased diffuse delta cortical source activity (p<0.0001) during the wakefulness period (Figure 2). No differences between these two last groups emerged in CSF neurodegeneration biomarkers, neuropsychological testing nor structural or functional MRI measures.ConclusionThe higher Frontal Delta Cortical Source activity across all vigilance conditions in t‐ADMCI subjects as compared to Nold, and the persistence of this result when compared to matched nt‐ADMCI patients, likely reflects the presence of dominant local delta rhythms, normally found during N3 and REM sleep, due to a low dopaminergic and cholinergic tone. Our findings might reflect a “disconnection” of frontal regions due to the loss of projections from monoaminergic subcortical nuclei, affected by early neuronal loss from AD neuropathology.
Cerebral amyloid angiopathy differently impacts gray matter microstructure in patients with Lewy bodies dementia and Alzheimer’s disease
Authors: Bommarito Giulia , Griffa Alessandra , Hall Caroline , Aleman‐Gomez Yasser , Hagmann Patric , Allali Gilles 
Published: January 2025

AbstractBackgroundCerebral amyloid angiopathy (CAA) has been reported in patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), with a similar prevalence from pathology studies.1,2 CAA typically affects posterior regions, but amyloid deposits have been observed in the striatum in patients with DLB and with hereditary CAA.1,3 Here, we postulated that CAA‐related amyloid pathology results in a different spatial pattern of damage in DLB with respect to AD, and we tested this hypothesis in vivo, by characterizing gray matter imaging features in patients with DLB and AD with and without CAA (CAApos, CAAneg).MethodIn this retrospective case‐control study, we included patients referring to the Leenaards Memory Center (Lausanne University Hospital), with a biological diagnosis of AD and a clinical diagnosis of DLB. Co‐occurrence of CAA was defined according to Boston criteria 2.0. Structural and diffusion‐weighted MRI data were processed, deriving volume, average fractional anisotropy (FA) and mean diffusivity (MD) for 13 cortical and subcortical regions.4 Multiple comparison correction was applied to all statistical tests.ResultEighty‐eight AD patients AD and 87 DLB patients were included (Table 1). Among AD and DLB patients, 15 (17%) and 23 (26.4%) presented with probable CAA, respectively (p= .132). MD and FA values of putamen, caudate and thalamus were significantly higher in DLB compared to AD patients (t(173) ranging from 2.05 to 2.91, p values ranging from .027 to .033 after multiple comparison correction).When comparing the 4 groups (AD‐CAApos, AD‐CAAneg, DLB‐CAApos, DLB‐CAAneg) subcortical microstructure significantly differed, and the ratio of limbic over basal ganglia FA values differentiated DLB‐CAApos from DLB‐CAAneg, AD‐CAAneg or AD‐CAApos (ANOVA F(3,171)= 3.44, p= .018, post‐hoc test corrected p values ranging from .021 to .041, Figure 1). No significant differences were found for posterior (occipital and parietal) regions metrics.ConclusionAs expected, patients with DLB and AD present a similar prevalence of CAA co‐pathology. However, in DLB patients, CAA associates with an increased basal ganglia over limbic anisotropy that could reflect higher iron content5 and is not observed in AD and DLB without CAA. These results might suggest that alpha‐synuclein and plaque amyloid depositions differently interact with CAA pathogenic pathway.
Omega‐6/Omega‐3 Ratio in Dementia Prevention ‐ Study Design and preliminary data of a feasibility study on lifestyle intervention
Authors: Rostamzadeh Ayda , Sannemann Lena , Bohr Lara , Gerards Michelle , Egert Sarah , Ramirez Alfredo , Jessen Frank 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is the most common etiology of dementia. As the progression of the disease may be slowed down by disease‐modifying therapies, but not stopped, research identifying further therapeutic approaches is necessary. Due to the multifactorial etiology of AD, targeting modifiable risk factors for dementia, including diet, is a starting point for preventive interventions. Currently, dementia prevalence is highest in North America and Western Europe, which correlates with an excess of saturated fat in the Western diet (WD). How precisely fatty acid dietary composition contributes to AD pathogenesis is poorly understood. Polyunsaturated fatty acids (PUFA), which account for 18% of total fat intake, include the essential fatty acids ω‐6‐linolenic and ω‐3‐alpha‐linolenic acid, which cannot be synthesized de novo and must be consumed in the diet. Omega ω‐6 and ω‐3 PUFA are found in high concentrations in the brain. Current findings indicate that a high ω‐6/ω‐3 ratio may contribute to a dysbalance between pro‐ and anti‐inflammatory processes and consequently accelerate or trigger neurodegenerative processes.MethodThis randomized‐controlled feasibility study investigates the effects of a 10‐week dietary intervention in a sample (n = 60) of cognitively healthy individuals from the Cologne Dementia Prevention Registry, who follow a WD. The dietary intervention consists of both a change in diet to reduce ω‐6 PUFA and supplementation with fish oil capsules to increase ω‐3 PUFA intake. The primary endpoint of the study is the reduction of the ω‐6/ω‐3 ratio, measured in serum phospholipids, including levels of ω‐6 and ω‐3 fatty acids. Secondary, exploratory endpoints include changes in dietary behavior, cognitive performance, markers of inflammation and oxidative status, epigenetic analyses (DNA methylation), and changes in lifestyle and well‐being.ResultWe present the rationale, design and preliminary results of a 10‐week dietary intervention trial in a cognitively healthy cohort.ConclusionThis study investigates the feasibility and effects of a lifestyle‐based intervention on the ω‐6/ω‐3 ratio and further biological and cognitive‐behavioral secondary outcomes. The results can inform future trials aimed at a deeper mechanistic understanding of the reduction of the ω‐6/ ω‐3 ratio in humans; eventually targeting clinical primary outcomes, such as cognition, over time.