bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term adiposity is associated with poorer cognitive performance in middle‐aged adults at high risk of Alzheimer’s disease
Authors: West Rebecca , Ravona‐Springer Ramit , Sharvit‐Ginon Inbal , Golan Sapir , Heymann Anthony , Beeri Michal Schnaider 
Published: December 2020

AbstractBackgroundThe impact of adiposity on cognition in older adults is well‐established. Alzheimer’s disease (AD) neuropathology begins accumulating years prior to symptoms; investigation of potential AD risk factors, such as adiposity, in middle‐aged adults may illuminate novel pathways underlying the earliest stages of cognitive decline. We examined the relationship of body mass index (BMI), and long‐term trajectories of BMI, with cognitive functioning in middle‐aged adults, participants of the Israel Registry of Alzheimer’s Prevention (IRAP Study), all members of the Israeli HMO‐ Maccabi Health Services, who are exquisitely well‐characterized for cardiovascular risk factors.MethodsIRAP follows middle‐aged offspring of AD patients (FH+; N=379) and offspring of non‐demented parents (FH‐; N=89). We examined relationships of BMI with global cognition and specific cognitive domains (executive functions, episodic memory, language, working memory). Linear regressions adjusting for age, sex, education, total cholesterol, systolic and diastolic blood pressure, glucose, creatinine, and diabetes status assessed associations of BMI (mean of all BMI measures in Maccabi for each participant) with cognition. Additionally, ANCOVAs were used to examine the association of long‐term trajectories of BMI (“normal, N=239; “overweight,” N= 115; and “obese, N=21” identified using SAS macro PROC TRJ), with cognition.ResultsHigher BMI was significantly associated with lower executive functions (p=.015), episodic memory (p=.032), and global cognition (p=.032), but not language (p= .729) or working memory (p=.391). Significant differences in cognition were identified for the BMI long‐term trajectories for executive functions (normal BMI=.12, overweight M=‐.24, obese M=‐.32, p=.007) episodic memory (.07, ‐.10, ‐.66, p=.021) and global cognition (normal M=.08, overweight M=‐.10, obese M=‐.40, p=.036), but not language (p=.181) or working memory (p=.855). Controlling for FH status did not alter these results.ConclusionHigher BMI was associated with lower executive functions, episodic memory, and global cognition in cognitively normal middle‐aged adults. This result is reinforced by the finding that long‐term trajectories of BMI (∼20 years of BMI measurements) were associated with these same cognitive functions; participants with long‐term normal BMI had the highest levels of cognition while those with long‐term obesity had the lowest. Adiposity may have a detrimental impact on the brain already in middle‐aged cognitively normal adults.
An 8‐year comparison of dementia prevalence in Korea: Results from the nationwide survey on dementia epidemiology of Korea, 2008 and 2016
Authors: Kim Ki Woong , Suh Seung Wan , Kim You Joung 
Published: December 2020

AbstractBackgroundIn many high‐income countries, the prevalence of dementia had been reduced over the past one or two decades. We investigated whether the prevalence of dementia had changed over the past 8 years in Korea.MethodWe had conducted the Nationwide Survey on Dementia Epidemiology of Korea (NaSDEK) in 2008 and 2016 on the Koreans aged 65 years or older who were randomly sampled from 15 administrative districts across the nation. We employed a two‐stage design; a screening phase using MMSE and a diagnostic phase using the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet. We used inverse probability weighting methods to estimate dementia prevalence adjusting for the sampling fraction and the response rate at each phase.ResultIn the NaSDEK 2008, 8,199 were sampled, and 6,141 and 1,673 participated in the screening and diagnostic phases, respectively. In the NaSDEK 2016, 5,056 were sampled, and 3,703 and 551 participated in the screening and diagnostic phases, respectively. According to the NaSDEK 2008, the prevalence of dementia in 2017 was estimated to be 13.7% (967,828). However, the NaSDEK 2016 revealed that the prevalence of dementia in 2017 would be 10.5%, (741,977), which was reduced than expected by the NaSDEK 2008 (OR 0.739, 95% CI 0.737‐0.742, p <.001).ConclusionA cohort effect of dementia prevalence was also found in Korea, with earlier‐born individuals having a higher risk of prevalent dementia than their later‐born counterparts.
Multi‐faceted brain changes associated with proximity to dementia onset: The PREVENT‐Dementia study
Authors: Mak Elijah , Dounavi Maria‐Eleni , Low Audrey , McKiernan Elizabeth , Carter Stephen F , Newton Coco , Williams Guy B , Ritchie Karen , Wells Katie , Sahin Zeynep , Terrera Graciela Muniz , Carriere Isabelle , Ritchie Craig W , Su Li , O'Brien John T 
Published: December 2020

AbstractBackgroundFirst‐degree relatives of people with dementia (FH+) are at increased risk of developing Alzheimer’s disease (AD). Identifying preclinical brain changes would facilitate both early quantifiable longitudinal disease monitoring and interventional trials. However, the literature of imaging changes in FH+ remains highly controversial. We aim to investigate “estimated years to onset of dementia” (EYOD) as a surrogate marker of preclinical progression and assessed whether FH+ approaching the parental age of dementia onset would express more severe patterns of longitudinal brain changes.Method89 FH+ persons underwent serial 3T‐MRI with T1‐MPRAGE, DWI and ASL (mean interval: 2 years). The longitudinal Freesurfer pipeline was used to segment hippocampal subfields and early‐AD regions. Partial‐volume corrected ASL data and DWI data were processed with FSL‐BASIL4 and DTI‐TK5. Small vessel disease was indexed with white matter hyperintensities (WMHs) (Figure 1). We applied linear mixed effects models to predict MRI changes relative to EYOD, accounting for age, gender, education and time from baseline. Secondary analyses examined the interaction of APOE‐ε4+ on proximity‐related brain changes.ResultA shorter EYOD was associated with progressive decrease in FA, increase in MD/RD and atrophy of the fusiform gyrus over time (Figure 2). Interaction analyses revealed that APOE‐ε4+ carriers showed significant longitudinal atrophy of the hippocampal subfields with shorter EYOD. In contrast, cortical perfusion increased before plateauing ∼10 years before estimated onset. There were no associations of EYOD with mean cortical thickness or WMHs (See Figure 3 for a summary of main findings).ConclusionOur findings represent the first extensive characterisation of longitudinal brain changes associated with proximity to dementia in FH+. Individuals who are approaching their parental age of dementia onset may be showing incipient brain abnormalities, particularly amongst APOE‐ε4 carriers. The specificity our findings in early‐AD regions also confer support to biological validity of EYOD as a stage marker of preclinical progression. Further ongoing clinical follow‐up of our sample would provide critical validation of these findings.
Combination of cognitive training and assessment using mobile games with elderly participants
Authors: Bonnechère Bruno , Van Hove Olivier , Samadoulougou Sékou , Klass Malgorzata , Kirakoya‐Samadoulougou Fati , Sahakian Barbara 
Published: December 2020

AbstractBackgroundThe decline of cognitive function and psychomotor slowing are two important issues related to aging. Numerous apps and games have been recently developed to challenge the brain with fun and motivating cognitive exercises. Previous studies suggest that these types of games are correlated with cognitive scales in the elderly with and without cognitive impairment. However, little is currently known about the potential of these types of interventions to impact cognitive performance positively, especially with healthy elderly. Therefore the objective of this study was to determine if it is possible to analyze changes in the scores of Cognitive Mobile Games (CMG) over a period of training to learn about the level of score improvement that participants of different ages can reach, as a proxy of cognitive performance.MethodsScores from 12,000 subjects aged above 60 years old using 5 commercial CMG were retrospectively analysed over a period of 100 training sessions. Results of the first session were compared using one‐way ANOVA and mixed models were used to subsequently investigate the progression of scores over the period of training for the different age groups.ResultsStatistically significant differences were found between the age groups and the initial scores of all the games. We observed that CMG scores increased for all participants, suggesting that all participants improved their cognitive performance. The rate of the score increase is strongly influenced by the age of the participants. There are significant interactions between the age of the participants and the session to predict the evolution of the scores.ConclusionThe current study provides two interesting insights: 1) users who train with the games improve regardless of age, suggesting that even older adults can improve their cognitive performance using new technology. 2) The presented method is a new and innovative way to assess cognitive function since older people perform less well on these types of games combined with previous findings, as expected. This kind of assessment could be used to monitor cognitive function during long term follow‐up and help early detection of cognitive decline and dementia.
The Positive and Negative Appraisals of Caregiving (PANAC) scale: A new measure to examine the caregiving experience in Alzheimer’s disease and related dementias
Authors: Galvin James E 
Published: December 2020

AbstractBackgroundCaregiving in Alzheimer’s disease and related dementias (ADRD) has long been examined as a monolithic experience describing the burdens and challenges that caregivers face. These studies typically explore one construct at a time, limiting the full understanding of the caregiver experience. In addition, there are few measures that examine the potential positive and rewarding experiences associated with caregiving. The absence of exploring these constructs may limit the exploration of how caregiver interventions may or may not succeed in meeting their primary outcomes. To address this, we developed a new scale: The Positive and Negative Appraisals of Caregiving (PANAC).MethodsThe PANAC scale was first explored in a developmental sample of 256 consecutive patient‐caregiver dyads and then validated in an independent sample of 274 consecutive patient‐caregiver dyads presenting to our center for clinical and/or research evaluations. Factor analyses using principle components with a Varimax rotation was performed revealing a two‐factor solution: Positive appraisals and Negative appraisals. Total PANAC scores, individual factors, and the ratio of positive to negative appraisals were examined for their psychometric properties and compared with patient and caregiver characteristics and caregiver reports of burden, grief, preparedness, mood, mindfulness, and care confidence.ResultsA two‐factor solution revealed a Negative Appraisal factor (Eigenvalue: 4.1; 25.8% of variance) and a Positive Appraisal factor (Eigenvalue 3.3; 20.9% of variance). Internal consistency was good with Cronbach’s alpha 0.74 for the total PANAC, 0.82 for Negative appraisals, and 0.80 for Positive appraisals (all F‐test p<0.001). Negative appraisals were highly correlated with patient cognitive performance, mood, quality of life, behavior, daily functioning, and frailty as well as with caregiver burden and depression. Positive appraisals were highly correlated with caregiver mindfulness. The ratio of Negative to Positive appraisals was derived to give an overall experience of the caregiver.ConclusionsThe PANAC scale is a useful global measure of the overall caregiver experience accounting for both negative and positive experiences associated with ADRD caregiving. The PANAC can be used to measure effectiveness of caregiver interventions and with the use of the Negative to Positive ratio, may be used to tailor programs to the individual caregiver.
Locus coeruleus signal intensity in progressive amnesia due to suspected non‐Alzheimer pathophysiology (SNAP)
Authors: Olivieri Pauline , Lagarde Julien , Lehéricy Stéphane , Valabrègue Romain , Caillé Fabien , Gervais Philippe , Bottlaender Michel , Sarazin Marie 
Published: December 2020

AbstractBackgroundSuspected non‐Alzheimer pathophysiology (SNAP) is underlain by different pathophysiological processes, among which the recently described Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE), which refers to patients with cognitive/memory impairment and limbic‐predominant TDP‐43 proteinopathy, associated or not with hippocampal sclerosis (HS) characterized by severe neuronal loss and gliosis in the CA‐1 and subiculum of the hippocampal formation (Besser and al. J Neuropathol Exp Neurol. 2019), or primary age‐related tauopathy (PART). The locus coeruleus (LC) is the major noradrenergic nucleus in the brain. In AD, the early LC neuronal loss could contribute to cognitive deficits, especially mental flexibility and memory retrieval impairments (Grudzien and al. Neurobiol. Aging, 2007). The involvement of LC alteration in amnestic SNAP patients has not been studied.MethodWe included 10 SNAP subjects defined by episodic memory deficit of the hippocampal type, normal CSF biomarkers profile and negative amyloid‐PET, 26 typical AD patients defined by clinical‐biological criteria (episodic memory deficit of the hippocampal type associated with CSF biomarkers AD profile and positive amyloid PET), and 14 controls with negative amyloid‐PET. All patients had a Clinical Dementia Rating scale ≤ 1. We used the LC signal intensity (LC‐I) on 3T MRI (Neuromelanin‐sensitive T1‐weighted images) as a marker of LC atrophy (Shibata and al. Magn Reson Med Sci. 2006).ResultsSNAP patients were older than AD patients (77.9 years and 70.8 years respectively, p=0.002), with a lower proportion of APOE4 carriers. We found no difference between SNAP and AD groups in neuropsychological scores, especially for MMSE, and verbal or visual episodic memory scores, as well as for hippocampal or entorhinal cortex volumes. We found a significant decrease of the LC‐I in SNAP patients compared with controls (p<0.003) or with AD patients (p<0.009). The episodic memory score was positively correlated with the LC‐I (r=0.33, p=0.034) in SNAP patients.ConclusionOur results suggest a significant LC alteration in patients with amnesia not due to AD. LC involvement could not be specific of AD pathology, and could also be part of the pathophysiological process of non‐AD diseases. Amnestic SNAP patients could thus benefit from innovative therapeutic approaches targeting the noradrenergic system.
Predictors of quality of life in Chilean family caregivers of people with dementia
Authors: Miranda‐Castillo Claudia 
Published: December 2020

AbstractBackgroundIn Chile, it is estimated that about 200.000 persons have dementia and this number will triplicate by 2020. Most care is provided by family caregivers who experience a negative impact on their physical and mental health. The aim of this study was to identify which factors from family caregivers and the person with dementia (PwD) were related to caregiver’s quality of life.MethodThis was a cross‐sectional study. The sample was composed by 90 family caregivers of PwD living in the community. Caregivers were interviewed about PwD’s quality of life, cognitive function, functionality and neuropsychiatric symptoms. They were also asked about their own quality of life, dysfunctional thoughts about caregiving, frequency and satisfaction with pleasant activities, burden, anxiety, depressive symptoms and the stress generated by PwD’s neuropsychiatric symptoms.ResultNone of the PwD’s factors were directly associated with caregivers’ quality of life. However, caregivers with higher levels of stress generated by PwD’s neuropsychiatric symptoms showed significant lower quality of life (r=‐0.22; p<.01). In addition, caregivers with higher levels of anxiety (r=‐0.45; p<.01), depression (r=‐0.45; p<.01) and burden (r=‐0.41; p<.01) plus lower frequency (r=0.31; p<.01) and satisfaction (r=0.41; p<.01) with pleasant activities had significantly worse quality of life. Finally, anxiety and depressive symptoms explained 25% of the variability in caregivers’ quality of life (F=14.1; p<.01).ConclusionIn order to improve family caregivers’ quality of life it is essential that dementia public policies address their needs. Interventions focused on improving their mental health should consider not only pharmacological approaches but also psychosocial and psychotherapeutic ones which could help with both, the management of PwD’s neuropsychiatric symptoms and the reduction of depressive and anxiety symptoms.
Development of a robust and stable mass based spectrometry method for analysis of Alzheimer’s disease biomarkers in human cerebrospinal fluid
Authors: Leslie Shannon N. , Wilson Rashaun , Trombetta Bianca A. , Kivisäkk Pia , Arnold Steven E. , Nairn Angus C. , Carlyle Becky C. 
Published: December 2020

AbstractBackgroundCurrent diagnostic tests for Alzheimer’s Disease (AD) rely predominantly on amyloid‐beta and tau measurements. However, these markers are insufficient to predict onset of disease, response to treatment, and do not capture the full spectrum of disease progression. Thus, a more expansive approach to diagnostic markers is required. Given the low abundance of putative proteins of interest in biofluids and the impact of relatively small changes in protein levels on the function of central nervous system, a highly sensitive but broad approach to protein monitoring is essential to identifying more comprehensive biomarkers. Data‐independent acquisition (DIA) mass spectrometry is an important tool for achieving this goal given both breadth and depth of protein analysis it enables. Thus, we developed a DIA method that allows for technically reproducible monitoring of thousands of peptides in human cerebrospinal fluid (CSF) to better characterize effective candidate peptides for the development of future targeted biomarker assays.MethodHuman CSF was analyzed via liquid‐chromatography tandem mass spectrometry (LC‐MS) with a data‐independent acquisition (DIA) technique. Stable isotopic peptides, enriched for putative proteins of interest to AD diagnostics, were used to create a heavy peptide standard mix. We characterized the stability and linearity of these peptides for use as a normalization tool. Utilizing this well characterized standard mix, we analyzed 30 samples from 15 patients collected at 2 different sites using DIA LC‐MS. Samples included a variety of disease states as well as longitudinal samples to assess both technical and biotemporal stability of peptides.ResultOur novel heavy peptide standard mix showed strong technical reproducibility and linear coherence with concentration. We were able to minimize and control for technical variation utilizing this standard mix; thus, enabling better cross‐sample comparisons of peptides. We characterized the technical reproducibility and stability of our methodology for thousands of peptides across a variety of technical and biological conditions. Overall, this methodology enables stable characterization of peptides across longitudinal samples and between disease conditions.ConclusionWe have developed a robust approach for stable monitoring of hundreds of proteins in human CSF, an important step toward utilization of novel biomarkers in AD diagnostics.
Sex differences in red blood cell α ‐synuclein protein and its heteroaggregates with amyloid‐β and tau in early Alzheimer’s disease
Authors: Prete Eleonora Del , Daniele Simona , Giampietri Linda , Galgani Alessandro , Piccarducci Rebecca , Gerfo Annalisa Lo , Petrozzi Lucia , Cavallini Chiara , Pietrobono Deborah , Trincavelli Maria Letizia , Frosini Daniela , Siciliano Gabriele , Bonuccelli Ubaldo , Ceravolo Roberto , Tognoni Gloria , Martini Claudia , Baldacci Filippo 
Published: December 2020

AbstractBackgroundA growing interest is recently focused on sex‐related differences in Alzheimer’s Disease (AD) pathology to optimize patients stratification and to personalize treatment. Among markers that are expression of this neurodegenerative disease, red blood cells (RBCs) levels of α‐synuclein (α‐syn) and its heterocomplexes with amyloid‐β (Aβ) and tau have been proposed as peripheral biomarker of AD. The aim of our study was to explore sex differences in RBC levels of α‐syn and its heterocomplexes in a group of AD/ mild cognitive impairment due to AD (MCI‐AD) patients and of Healthy Controls (HC).MethodDifferences between male and female sex matched for age were investigated in RBC regarding homo‐ and heteroaggregates of α‐syn, Aβ and tau [total tau (t‐tau) , Aβ42 ,total α‐syn (t‐ α‐syn), oligomeric α‐syn (o‐α‐syn), α‐syn/Aβ and α‐syn/tau] in a cohort of AD/MCI‐AD patients in early stages of disease and in HC.ResultIn our study 147 subjects were enrolled, 47 AD, 40 MCI‐AD and 60 HC. In AD/MCI‐AD cohort we identified significant differences in t‐tau levels between sex (p=0.010), with higher value in men than women (6.1±5.9ng/mg vs 4.0±6.8ng/mg), no significant differences Aβ42 , t‐α‐syn, o‐α‐syn, α‐syn/Aβ and RBC‐α‐syn/tau. In HC group we reported significant differences in Aβ42 (p=0.014) and α‐syn/tau (p=0.030). In particular, women presented higher Aβ42 and α‐syn/tau compared to men (18.22±12.19 ng/mg vs 13.31±13.86 ng/mg and 2.93±1.67 ng/mg vs 1.95±1.75 ng/mg, respectively). Mean age for the group AD/MCI‐AD was 72.5±6.61yy for women and 71.9±6.43 yy for men, while mean age was 62.38±8.48 yy for women and 66.20 yy for men in HC group. Comparison in biomarkers between AD/MCI‐AD and HC was not performed due to significant differences between age p<0.001 in women and p=0.003 in man.ConclusionSex differences in RBC biomarkers for AD were identified in AD/MCI‐AD patients and in HC. Women reported higher levels of RBC Aβ42 and RBC α‐syn/tau than men in HC, while RBC t‐tau concentrations were higher in men than in women in AD/MCI‐AD cohort. Although additional investigations in larger samples are needed to confirm our data, a different distribution of neurodegenerative biomarkers in men and women is likely.