bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social network as a catalyzer of adherence to risk factor control in subjects with a subjective memory complaint
Authors: Cristalli Carolina Agata Ardohain , Seminara Emiliana , Hernández Micaela A , Elgani Sofía Alejandra , Calandri Ismael Luis , Allegri Ricardo Francisco 
Published: December 2023

AbstractBackgroundSubjective memory complaint (SMC) is defined as the perception of memory deficits despite a normal cognitive assessment, it is related to long‐term cognitive decline risk. The guidelines recommend medical advice about risk factor control, a healthy diet, and regular exercise for lower risk. However, there is no evidence that would guarantee good adherence. Social networks are conduits of support, information, and health behavior flows, they may have an impact on SMC adherence to the suggested changes. Our aim is a) to assess long‐term adherence of SMC to lifestyle changes b) to evaluate social networks as a predictor of adherence.MethodsProspective cohort study recruiting SCM participants with a normal UDS3 neuropsychological battery. Participants were evaluated on individual risk based on CAIDE score and received guideline‐based recommendations about lifestyle changes. Subjects were re‐evaluated 6 months after recommendations to assess their adherence to a healthy diet (MIND score), physical activity (IPAQ), risk factor control, and their social network (Figure 1). We fitted a generalized linear model to predict IPAQscore and MINDscore with social network features.ResultsWe recruited 200 participants (age 68.1 ± 6.5; 62% female; 57% first‐degree family history of dementia, and 15.91±2.28 years of education). Participants presented a 7.55±2.04 CAIDE score (Table 1): 37% high blood pressure, 51% obesity, dyslipidemia 43%, Social isolation 25%, 51% sedentarism, 9% smoking, and 22% heavy drinking. Six months after medical advice, 15% stopped drinking, 5.1% quit smoking, 37% started physical activity, and 66% a healthy diet. Regarding social networks, the median size of the network was 8 IQR[5‐12], 50% were kin, gender diversity: IQV = 0.77; 50% IQR[20%‐60%] sedentary, 20% IQR[0%‐44%] unhealthy diet. The percentage of sedentary social network members was a predictor of the intensity of the weekly physical activity of participants (in METS/minutes/week)(β ‐2.82 95%CI[‐4.7,‐9.27] p = 0.005) (Table 2).ConclusionParticipants showed good adherence to the proposed intervention. Social networks have an impact on adherence and it is a potential target to prevent dementia.
Preliminary Effects of Aerobic Exercise, Training Dose, and Cardiorespiratory Fitness on Resting Plasma Neurotrophic Factors in Alzheimer’s Dementia in the FIT‐AD Trial
Authors: Salisbury Dereck , Li Danni , Todd Michael , Ng Ted K.S. , Yu Fang 
Published: December 2023

AbstractBackgroundVascular factors are increasingly recognized for their roles in the pathogenesis and progression of Alzheimer’s dementia (AD). Cardiorespiratory fitness (CRF), a physiologic indicator of cardiovascular health, and plasma neurotrophic factors, endogenous soluble proteins in the periphery, have been linked to cognition, brain structure and function, and AD and are modifiable by aerobic exercise (AEx), but their interplay remains poorly understood. The objective of this pilot study was to estimate the effect sizes of 6‐month AEx on resting plasma neurotrophic factors and the relationships of CRF and exercise dose with change in resting plasma neurotrophic factors in AD.MethodThis study was a pilot blood ancillary study of the FIT‐AD Trial that randomized participants to 6‐month AEx or stretching control on a 2:1 allocation ratio. The blood study enrolled 26 participants (AEx Group [n = 18] and stretching control [n = 8]). Resting plasma brain‐derived neurotrophic factor (BDNF), irisin, fibroblast growth factor‐21 (FGF‐21], and insulin‐like growth factor‐1 (IGF‐1), and CRF (peak oxygen consumption) were assessed at baseline, 3 and 6 months. Exercise dose was calculated by the heart rate physical activity score (HRPAS) method.ResultThe sample was 77.6±6.99 years of age and had 15.4±3.00 years of education on average. Sixty‐five percent of the participants were male and 96.2% carried at least one copy of APOE e4. Most 6‐month between‐group effect sizes were small except for irisin (d = ‐0.44), indicating that the irisin levels decreased in the AEx group relative to stretching control. The association between exercise dose and changes in CRF with changes in neurotrophic biomarker were weak (r2 ≤ 0.025).ConclusionThe effects of exercise on BDNF, irisin, IGF‐1, and FGF‐21 may be heterogeneous in AD. Weak associations of exercise dose and CRF changes with changes in resting neurotrophic biomarkers were seen. There were weak associations of exercise dose and CRF changes with changes in resting neurotrophic biomarkers. Our findings need to be validated in future, adequately powered exercise studies in AD.
Experience in mixed vascular dementia in the genetic bank of the School of Medicine, University of Buenos Aires, Argentina
Authors: Brusco Luis Ignacio , Muchnik Carolina , Olivar Natividad 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common form of dementia. The sporadic forms represent 95% whereas 5% assumes to the familiar forms. Among the genetic factors of Alzheimer’s disease is genotype for APOE variant e4 which is associated to a major risk of suffering the illness. There is a mixed vascular component, that is to say vascular dementia and Alzheimer’s disease which might be related to the same gene APOE‐e4 in homozygous or heterozygous. To analyze the influence of APOE genotype and the mixed vascular component in the development of AD and the allelic and genotypic distribution of APOE in our population is our aim.MethodIn the genetic bank of dementias of the School of Medicine (of the) University of Buenos Aires we have selectively studied those patients with vascular commitment and Alzheimer’s disease. It was noted the association of risk between this gene and Alzheimer’s disease in our population, as well as is possible it’s association with the mixed component of the patients with dementia.

Population under study: 1) AD Patients
: The clinical diagnosis was made according to the NICDS‐ADRDA criteria. (n = 49, 20 men and 29 women).
2) >60 years Controls
: subjects with no history of neurological diseases (n = 31.8 men and 23 women).
3) Population Controls
: (n = 70, 24 men and 46 women).ResultA significant association between APOE‐ ε4 allele, mixed vascular component and AD was found. Even higher than the ApoE‐4 component of AD. About the influence of the genotype in the AD of delayed beginning aour results was: controles vs. AD, OR: 3,70 (1,43 ‐ 1,57), p<0,01 / controles>60 years vs. AD, OR: 4,32 (1,47 ‐ 12,43), p<0,02. And we found the relation between Apo ‐ e Genotype in Mixed Dementia and AD was AD vs controles, OR = 4,1, RR = 1,6, p<0,0001 / DM vs controles, OR = 10,3, RR = 4,1, p<0,0005ConclusionOur results suggests that it may correspond to an increased risk of outbreak of the physiopathology of AD in patients with vascular injury and / or cerebral hypoxia. The APOE‐4 would be a risk factor for vascular injury remaining unprotected brain, resulting in mixed demetia.
SARS‐CoV‐2 Associated Neurocognitive Disorder (SAND): Molecular validation of a pathogenetic hypothesis
Authors: Vavougios George D. , Mysiris Dimitrios , Foka Pelagia , Mavridis Theodore , Stavrou Vasileios , Papaggeli Olga , Zarogiannis Sotirios G , Xiromerisiou Georgia , Artemiadis Artemios , Gourgoulianis Konstantinos , Snyder Heather M , de Erausquin Gabriel A. , Hadjigeorgiou Georgios M. ,   COVALENT
Published: December 2023

AbstractBackgroundType I interferon signalling dysregulation is a hallmark of SARS‐CoV‐2 infection and among significantly perturbed pathways in Alzheimer’s disease. In a previous study, we predicted the involvement of this pathway in the development of SARS‐CoV‐2 Associated Neurocognitive Disorder (SAND) via a crosstalk between peripheral immunity and the CNS. The purpose of this study is to determine whether current data support provide external validation to our pathogenetic hypothesis.MethodData for our validation analyses were leveraged from studies of frontal cortex (FC) transcriptomes donated by Alzheimer’s disease and COVID‐19 patients vs. controls, respectively. An additional dataset of nasal epithelial cells from COVID‐19 patients was also used as a putative crosstalk site. Enrichment analyses were employed to provide an unbiased estimate of the enrichment of Type I interferon responses. Furthermore, we performed a literature search in order to identify studies on the effects of COVID‐19 on two different settings: (a) to determine the effects of peripheral exosome cargo on CNS tissue (b) to determine the cargo of neuronal‐derived exosomes. For enrichment analyses, a false discover rate (FDR) <0.05 was considered statistically significant.ResultThe type I interferon pathway (IFN‐I; GO:0060337) was significantly enriched in both Alzheimer’s disease and COVID‐19 FC transcriptomes, as well as nasal epithelia of COVID‐19 patients. Common genes in both IFN‐I FC signatures included PSMB8, IP6K2, IFI35, EGR1, ISG20, MYD88, IFITM1, SP100, GBP2, IFITM3, OASL, IRF1, IRF2, MX2, IFNA2, IRF9, IFIT3, STAT2, HLA‐C, SAMHD1, IFI27, IFITM2, IRF7, BST2. At least one study reports on miR‐148a and miR‐590 as exosomal cargo of infected non‐neuronal cells capable of affecting IFN‐I responses and inducing microglial activation, supporting the role of exosomes as facilitators of IFN‐I crosstalk between the periphery and the CNS. Correspondingly, at least one study reports on proteopathic seeds as cargo of neuron‐derived exosomes.ConclusionIndependent studies and data support continue to corroborate our hypothesis that type I interferon pathway dysregulation as a result of peripheral – CNS immune crosstalk may mediate neuroinflammation and Alzheimer’s disease‐like pathology as observed in SAND.
Multi‐modal Imaging‐based peudotime analysis for AD progression
Authors: He Bing , Risacher Shannon L. , Saykin Andrew J. , Yan Jingwen 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) progresses along a continuum and begins many years before symptom onset. AD takes a long progression time, making it hard to study the entire spectrum of AD development. Pseudotime analysis widely used in cell lineage analysis have been applied to AD gene expression data to understand the molecular changes along progression. In this work, we performed a neuroimaging‐based pseudotime analysis to explore the progression patterns of different imaging modalities.MethodData were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://adni.loni.usc.edu/). Data from three imaging modalities were collected including MRI (N = 1684), Amyloid (N = 1041), and Tau (N = 540) (Table.1). Out of those, 223 subjects have all three modalities. We tested four different pseudotime analysis tools: PHATE, MONOCLE3, Slingshot, and Destiny. MRI, Amyloid, Tau, and the combined multi‐modality data were used to estimate the pseudotime respectively. Only PHATE returned non‐reversed pseudotime and clear disease trajectoriesResultAmyloid derived pseudotime best captures the continuum of disease progression and differentiate diagnosis groups the best (Fig.1(b,f)). It also showed better correlation with clinical cognition scores than the composite amyloid measure (Fig.2(b,d)). Multi‐modality derived pseudotime reveals turning point of Amyloid and Tau. We found that the accumulation of Amyloid starts to accelerate when the composite SUVR reaches ∼1.2, which agrees well with existing findings (Fig.2(g,h)). Such turning point does not exist for amyloid derived pseudotime. It also reveals temporal order of brain changes within and across modalities (Fig.2(e,f)), where we observed overall amyloid changes starts early (i.e., small pseudotime) and accelerates earlier than overall brain atrophy and Tau deposition. With a closer look into Tau regions, we found Tau deposition in BRAAK 1 regions accumulates in a faster rate than those inBRAAK34 and BRAAK56 regions.ConclusionPseudotime analysis has a great potential for us to better understand the progression of Alzheimer’s disease. New approaches to fully leverage the longitudinal imaging data could provide a refined view of imaging changes and their co‐occurance pattern along AD progression. Longitudinal data in pseudotime analysis could also help capture the subtle changes in very early stage and therefore would likely provide some valuable insights to improve early diagnosis.
A supervised machine learning approach to predicting mild cognitive impairment among diverse Hispanics/Latinos: The SOL‐INCA Study
Authors: Kuwayama Sayaka , González Kevin A , Márquez Freddie , Gallo Linda C , González Hector M , Tarraf Wassim 
Published: December 2023

AbstractBackgroundExisting literature highlights the need for better risk assessment of mild cognitive impairment (MCI) to mitigate the onset and burden of Alzheimer’s Disease and Related Dementia (ADRD) through earlier interventions. Hispanics/Latinos are the largest US ethnic/racial minority, at higher risk for developing ADRD compared to Non‐Hispanic Whites, but underrepresented in dementia‐related research. This study develops prediction models for targetable protective and risk factors of MCI in diverse, middle‐aged Hispanics/Latinos in the US.MethodWe use data (n = 4246, average baseline age = 56‐years) from the Hispanic Community Health Study/ Study of Latinos (HCHS/SOL; 2008‐2011), a multisite prospective cohort study of diverse Hispanic/ Latinos, and its ancillary study, the SOL‐Investigation of Neurocognitive Aging (SOL‐INCA). Our outcome is prevalent MCI at SOL‐INCA visit (average 7‐years after the baseline) operationalized based on National Institutes of Aging‐Alzheimer’s Association criteria. Using nearly 40 baseline indicators representing (1) sociodemographic characteristics, (2) childhood factors, (3) acculturation factors, (4) biological and (5) behavioral markers, and (6) mental and (7) functional health, we compared a supervised machine learning (Random Forest; RF) and a standard statistical technique (logistic regression; LR) in identifying predictors. Additionally, to evaluate RF as a feature selection tool, we estimated Area Under the Curve (AUC) from LR using all factors and a subset of factors identified as important by RF.ResultLR identified socioeconomic conditions and mental and physical health scores as among the leading factors predicting MCI. RF identified a larger subset of predictors and differed from LR in ranking the relative importance of common predictors. Removal of factors identified as insignificant in predicting MCI by RF (n = 17) slightly improved classification performance in LR (AUCall factors = 0.692, AUCsubset by RF = 0.697).ConclusionSupervised machine learning (ML) identified different predictors for MCI compared to standard methods and was compelling as a feature selection method. This suggests potential value of ML to focus on significant predictors for MCI prediction. Substantively, our findings emphasize the importance of accounting for life‐course risk and protective factors for predicting cognitive health. Further investigations are needed to test additional ML modalities and better understand how complex interactions of life‐course multi‐domain factors can be addressed through interventions.
Angiotensin‐converting enzyme‐1, ACE‐1, and ACE‐2 are dysregulated in Alzheimer’s disease and related to ACE1 genotype
Authors: Guzel Ozge , Tayler Hannah Mary , Miners James Scott , Kehoe Patrick Gavin 
Published: December 2023

AbstractBackgroundThe renin‐angiotensin system (RAS) is dysregulated in Alzheimer’s disease (AD): angiotensin‐converting enzyme (ACE‐1) activity, a rate‐limiting enzyme in the disease‐associated classical RAS (cRAS) pathway, is elevated, whereas ACE‐2 activity, a central mediator of the counter‐regulatory protective pathway (rRAS) (that generates Ang‐(1‐7) from Ang‐II) is defective. Previous meta‐analyses, more recently confirmed in GWAS studies, indicate that ACE1 variants, including an insertion (I)/deletion (D) (indel) polymorphism at intron 16, are risk variants in AD. In this study, we have determined if ACE‐1 and ACE‐2 are dysregulated in AD in relation to ACE1 variant (rs4343) (a proxy marker for the more commonly studied indel polymorphism).MethodWe studied brain tissue from the frontal and parietal cortex from 147 dementia cases (AD (n = 94) and vascular dementia n = 20 and mixed AD/VaD (n = 33)) and 104 age‐matched controls from the South West Dementia Brain Bank, University of Bristol. ACE‐1 and ACE‐2 protein levels were measured by ELISA, and enzyme activities were measured using fluorogenic peptide substrate assays. ACE1 (rs4343) polymorphism was genotyped by PCR.ResultACE‐1 protein level was increased (p<0.0001) and ACE‐2 protein level reduced (p = 0.0103) in AD cases compared to controls in the parietal cortex. In contrast, no significant changes in protein level were observed in the frontal cortex. ACE‐1 enzyme activity was elevated (p<0.0001) as was ACE‐2 enzyme activity in both frontal and parietal cortices (p<0.0001 and p = 0.001 respectively) in AD. Individuals with I/I compared with D/D and I/D genotypes in AD had unchanged ACE‐1 level (p = 0.079), lower ACE‐1 enzyme activity (p = 0.029), higher ACE‐2 level (p = 0.011) and unaltered ACE‐2 enzyme activity (p = 0.085) in the frontal cortex.ConclusionThese data confirm our previous findings showing that RAS is dysregulated in AD. Interestingly, we report regional differences in RAS signalling in AD and a reciprocal relationship between ACE‐2 protein level (reduced) and enzyme activity (increased) in AD that warrants further investigation. RAS appears to be most dysregulated in individuals with an I/I genotype in AD.
Event‐related potential signatures of episodic memory decline predicting progression to Alzheimer’s disease in asymptomatic at‐risk subjects: a longitudinal study.
Authors: Pereira Filipa Raposo , Chaumon Maximilien , Dubois Bruno , La Corte Valentina , George Nathalie 
Published: December 2023

AbstractBackgroundThe challenge in Alzheimer’s disease (AD) research ‐the world most prevalent dementia‐remains on finding preclinical markers that can predict progression to the disease. In this respect electrophysiological (EEG) measures seem promising, based on their sensitivity to the appearance of subtle episodic memory (EM) alterations, which become an AD risk‐factor when in the presence of B‐amyloid burden (AB+; AD‐biomarker) (Paitel et al., 2021; Olichney et al., 2011). We aimed to identify event‐related potential (ERP) signatures of AD‐linked EM alterations in elder cognitively normal subjects at‐risk for AD.MethodsEEG data was collected longitudinally with an EGI 256‐channels cap, over 6 yearly sessions, in 15 controls (AB‐), 15 non‐converters (AB+), and 15 converters to prodromal‐AD (AB+; who converted during follow‐up but were only considered before diagnosis) from the INSIGHTpre‐AD cohort. We analysed the typical ERP response to a classic task of verbal memory recognition of old or new words (i.e. P3 and FN400 [0.25‐0.34 and 0.51‐0.57ms], P600 [0.62‐0.77ms], and monitoring [0.87‐1.04ms]). The new words were related to the old words (previously encoded) either in their number of repetitions (NR) or in their semantic content but presented once (NU). Source‐localization analysis of these data is currently underway.ResultsDuring follow‐up, the converters showed increased reaction time and decreased accuracy in word recognition when compared with the other groups. The converters significantly showed greater mean amplitude in the fronto‐parietal left and parieto‐occipital central regions typically linked to EM recollection, in the 0.25‐0.34 ms time‐window when compared with the controls, and in the 0.51‐0.57ms time‐window when compared with the non‐converters. Through our period of interest, old words activated mostly central‐posterior left regions (semantic networks/familiarity), NR words activated the frontal right region (i.e. novelty detection), and NU words frontal‐temporal right regions (semantic interference detection).ConclusionOur findings show amplitude differences associated with AD‐linked EM alterations years before individuals are diagnosed, representing potential ERP signatures of progression to AD in at‐risk individuals, while they remain cognitively normal. Anticipation of diagnosis contributes to the development of more effective tailor‐made treatments that potentially ease quality of life of patients and caregivers.
Feasibility of a Synchronous, Remoted‐Delivered, Aerobic Exercise Training Program in Rural‐Dwelling Adults with Subjective Cognitive Decline ‐ The MN RIDE Pilot
Authors: Salisbury Dereck , Soderlund Patricia R , Fergen Joshua , Cruikshank Kirsten R , Shaughnessy Keith , Anderson Timothy , Warry Wayne , Jacklin Kristen 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD), the subjective experience of worsening memory or cognition, is one of the earliest noticeable symptoms of Alzheimer’s disease and related dementias (ADRD), and offers a therapeutic window where interventions have strong potential to prevent or delay the progression to the ADRD. Out of all the modifiable risk factors for ADRD, physical inactivity is the strongest; therefore, it is no surprise that exercise is linked to a 30‐40% risk reduction for ADRD, with moderate intensity being the most beneficial. Rural communities have greater barriers in participating in exercise due to lack of social support, travel/weather problems, and lack of facilities/equipment. The purpose of this pilot study was to implement and evaluate the feasibility of a synchronous, remoted‐delivered, aerobic exercise (AEx) training program in persons with SCD living in rural areas.MethodThe MN RIDE Pilot Study employed a single group, pre‐posttest design. Participants were shipped all needed equipment to complete the intervention (cycle, heart rate monitors, etc.). All AEx sessions were supervised remotely via smart devices and Zoom® by an exercise physiologist. AEx was prescribed as progressive, moderate‐intensity cycling for 20‐50 minutes, 3 times/week for 3 months (36 sessions). Intensity was evaluated using the Borg Rating of Perceived Exertion (RPE) 6‐20 scale and heart rate max (HRmax) methods. Moderate intensity was defined as RPE 13 and HRmax 64‐76%. Feasibility was assessed by session attendance, intensity adherence, and presence of adverse events.ResultThe average age of the study sample (n = 9) was 57.44±7.16 years old (average age of SCD onset 53.44 [7.47] years old) with 14.00±5.57 years of education and 77.8% female. Out of the possible 324 sessions scheduled, 276 were attended (86% session adherence). Average intensity metrics achieved over the AEx sessions were 13.2 (0.5) and 72.0 (7.9) for RPE and HRmax respectively. No adverse events were reported.ConclusionOur study provides preliminary evidence of the feasibility of AEx telerehabilitation program designed to reduced ADRD risk in persons with SCD living in underserved rural communities. AEx telerehabilitation in rural communities should be further explored given AEx’s potential to reduce ADRD risk.