bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between psychophysiological stress responses, inflammatory markers, and CSF biomarkers in the spectrum of Alzheimer’s disease
Authors: Oh Hwamee , Leung Hoi‐Chung , Canli Turhan , Slifstein Mark , Park Elliot Y. 
Published: December 2021

AbstractBackgroundAlthough genetic factors associated with the aggregation of misfolded proteins clearly play a role in Alzheimer’s disease (AD), several individual difference factors have been seen to confer an increased risk for the clinical manifestation of AD as well as the development of AD pathology. One of the key factors is an individual’s susceptibility to psychological stress. The goal of this study was to examine the relationships between psychophysiological stress responses measured by plasma stress hormones and neuropsychiatric symptoms, inflammatory markers, and AD pathology along the spectrum of AD.MethodAlzheimer’s Disease Neuroimaging Initiative (ADNI) consists of 819 adult subjects— 229 cognitively normal older adults (CNs), 398 participants with mild cognitive impairment (MCIs), and 192 patients with AD. Of these subjects, we included 58 CNs, 396 MCIs, and 112 AD patients whose plasma stress measures were available. Plasma cortisol and cytokines and CSF Aβ1‐42, t‐tau, and p‐tau181 data were downloaded from ADNI. Neuropsychiatric Inventory (NPI‐Q) total scores were used to indicate a psychological stress level.ResultAD stages were significantly related to the level of plasma cortisol and NPI‐Q total scores showing that AD patients exhibit the highest level of cortisol and greater severity of psychological symptoms followed by MCIs and CNs. AD stages were also significantly related to the level of inflammatory markers measured by cytokines, although the level of inflammatory markers in relation to the diagnostic groups varied across different types of cytokines. Plasma cortisol levels did not relate to concurrent levels of CSF Aβ1‐42 either across diagnostic groups or within diagnostic groups. Higher plasma cortisol, however, corresponded to higher CSF p‐tau among CNs, but not in MCIs and ADs.ConclusionPsychophysiological stress responses and inflammatory markers are significantly associated with the disease severity. A positive relationship between plasma cortisol level and CSF p‐tau in CNs may indicate a role of individuals’ susceptibility to stress in neuronal hyperexcitability in the early stage of AD and confer a risk of neurodegeneration and the development of AD. Alleviating stress and regulating stress responses may be important modifiable factors that help prevent AD.
Arabic translation and cross‐cultural adaptation of the Bristol Activities of Daily Living Scale (BADLS)
Authors: Alkeridy Walid Ahmed , Muayqil Taim A , Al Khalifah Reem Abdullah , Mohammedin Ahmed S , Khallaf Roaa A. , Bucks Romola S 
Published: December 2021

AbstractIntroductionThe prevalence of dementia is expected to increase exponentially in developing countries over the next few decades.1, 2 Arabic language is widely spoken across the middle east and north Africa, where dementia diagnosis remains challenging.3 Many factors contribute to the underdiagnosis of dementia in Arabic speaking countries including the lack of validated functional assessment tools for patients with cognitive impairment.2, 4 The aim of this study is to translate, cross culturally adapt and validate the widely used Bristol Activity Of Daily Living Scale (BADLS)5 to the Arabic language.MethodsFirst the BADLS was translated to the Arabic language by two independent bilingual experts. The Arabic version was then back translated to English by two independent translators. Then reviewed by expert panel including the original author to keep original meanings, check accuracy and standardization. A pilot study was done for Cognitive Debriefing. Expert panel discussion was done to review cognitive debriefing and finalize. Criterion validity is tested against the validated Arabic version of the Katz Index of Independence in Activities of Daily Living and the Arabic version of the Montreal Cognitive Assessment (MOCA) test.ConclusionTo our knowledge this is the first study to translate the BADLS to the Arabic language. The Arabic BADLS will enable the early and accurate diagnosis of dementia for Arabic speaking patients and caregivers. References: 1. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396(10248):413‐446. 2. Epidemiology of Alzheimers Disease and Dementia in Arab Countries: A Systematic Review. Behavioural Neurology. 2019. 3. Benabdeljlil M. Assessment of cognitive disorders in the Arabic language. Journal of the neurological sciences. 2019;405(S):66‐67. 4. Abou‐Mrad F, Chelune G, Zamrini E, Tarabey L, Hayek M, Fadel P. Screening for dementia in Arabic: normative data from an elderly Lebanese sample. The Clinical Neuropsychologist. 2017;31(sup1):1‐19. 5. Bucks RS, Ashworth DL, Wilcock GK, Siegfried K. Assessment of Activities of Daily Living in Dementia: Development of the Bristol Activities of Daily Living Scale. Age Ageing Age and Ageing. 1996;25(2):113‐120.
Tau deposition is associated with grey matter network breakdown across different stages of the Alzheimer’s disease continuum
Authors: Pelkmans Wiesje , Ossenkoppele Rik , Dicks Ellen , Strandberg Olof , Barkhof Frederik , Tijms Betty M. , Pereira Joana B. , Hansson Oskar 
Published: December 2021

AbstractBackgroundChanges in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD), and have been associated with amyloid‐β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau‐related connectivity changes across different stages of AD might be expected.MethodIn this study, we examined the relationship between tau aggregation (using tau positron emission tomography [tau‐PET]) and grey matter networks (using T1‐weighted images) in 533 individuals (178 Aβ‐negative cognitively unimpaired (CU) subjects, 105 Aβ‐positive CU subjects (preclinical AD), 122 Aβ‐positive patients with mild cognitive impairment (prodromal AD), and 128 patients with AD dementia) from the Swedish BioFINDER‐2 study (Table 1). Single‐subject grey matter networks were extracted and graph theory properties including degree, connectivity density, clustering coefficient, path length, and small world topology were calculated. Associations between tau‐PET values and global and regional network measures were examined using linear regression models adjusted for age, sex, total intracranial volume, and connectivity density.ResultAcross the whole sample, we found that higher tau load in the temporal meta‐ROI was associated with significant changes in degree, connectivity density, clustering, path length, and small world values of the brain network (all p < 0.001; Fig. 1, 2), indicative of a less optimal network organization. Already in early disease stages, higher tau PET signal was associated with lower clustering and path length (Table 2). In more advanced disease stages elevated tau pathology was progressively associated with more advanced brain network abnormalities.ConclusionThese findings suggest that tau pathology is associated with a reduced communication between neighbouring brain areas and an altered ability to integrate information from distributed brain regions indicative of a more random network topology across different AD stages.
Identifying cognitive trajectories and predicting rapid decline of cognitive function in early Alzheimer’s disease
Authors: Lin Yung‐Shuan , Fuh Jong‐Ling 
Published: December 2021

AbstractBackgroundThe clinical manifestations and progression of cognitive function vary between patients with Alzheimer disease (AD) and mild cognitive impairment (MCI). Predicting disease course is important for families and clinicians because most patients experience progressive and irreversible cognitive decline despite variations.MethodsThis study sought to identify groups of patients following a similar trajectory of cognitive decline over time, and then developed a prediction model to identify patients at higher risk for a speedy cognitive decline. This study was conducted on a clinic‐based cohort of 233 early AD and MCI patients who converted to AD within 2 years in Taiwan. A group‐based trajectory modeling technique characterized the trajectory groups of Mini‐Mental State Examination (MMSE) scores over time. Feature‐selection strategy was then used to investigate predictors of the trajectory of rapid cognitive decline. Finally, multivariable logistic regression (LR) was applied to predict the trajectory group membership from the predictors.ResultsThe best‐fitting model includes two meaningful trajectories: Group 1 shows a rapid decline in the MMSE scores over time (decrease of 5.4±3.9 points within 2 years); Group 2 shows a slow progression (decrease of 1.2±3.9 points within 2 years). The baseline MMSE score, instrumental activities daily living (IADL) total score, and APOE ε4 status are significant predictors in the prediction model for classifying the trajectory of cognitive decline. After bootstrapping validation, the performance of the LR model using these predictors to predict trajectory groups shows 85.3% of area under curve (AUC), 79.0% of sensitivity, 73.1% of specificity, and 75.4% of predictive accuracy.ConclusionsAmong various biomarkers and neuropsychological battles for patients with AD or MCI, baseline MMSE score, IADL total score and APOE ε4 status are the ones important and unchallenging to obtain in dementia clinics. The LR model for the prediction model is easy to understand and apply in the clinical practice. This model gives clinicians and patients a glimpse of future cognitive progression and aids further healthcare planning.
An individualized systems model to optimize Alzheimer’s disease prevention strategies
Authors: Uleman Jeroen F , Quax Rick , Melis René JF , Hoekstra Alfons , Rikkert Marcel GM Olde 
Published: December 2021

AbstractBackgroundA large number of biopsychosocial factors are implicated in the prevention of Alzheimer’s Disease (AD). These factors are not independent causes but part of a complex causal network that underlies the condition. Computational models that would capture this system‐wide multicausality could help identify causal pathways and inform multifactorial prevention strategies.MethodWe developed a system dynamics model (SDM) from a causal loop diagram that was parameterized using empirical data from multiple cohorts (including the Alzheimer’s Disease Neuroimaging Initiative). The SDM contains over 20 known risk factors and pathophysiological processes, including blood pressure, smoking, neuronal dysfunction, and amyloid‐beta and phosphorylated tau burden. We simulated 5‐year cognitive decline trajectories for individuals and explored several “what if” scenarios regarding the effect of changes in modifiable risk factors on cognitive decline.ResultOur SDM was able to simulate the cognitive decline trajectories of individuals with good accuracy (< 20% mean absolute percentage error). These predictions also generalized well to an independent test sample from the same data set (<2% error increase). The effect of changes in modifiable risk factors on cognitive decline in the SDM were checked against literature reported ranges. We also developed a workflow to further calibrate and validate the SDM.ConclusionOur SDM demonstrates the feasibility of system‐wide modelling approaches for AD prevention. Such a simulation model could eventually be used to better understand the interactive effects of modifiable risk factors on AD pathophysiology and help optimize individualized prevention strategies.
Development of a tool to motivate for healthy behaviors to prevent dementia in Cuba, Puerto Rico and Dominican Republic
Authors: Peeters Geeske , Almirall‐Sanchez Arianna , Llibre‐Guerra Jorge J , Jiménez‐Velazquez Ivonne Z , Acosta Daisy M , Lawlor Brian , Anne Kenny Rose , Yaffe Kristine , Llibre‐Rodriguez Juan J 
Published: December 2021

AbstractBackgroundPrevious research showed that up to 56% of all dementia cases in Latin America could potentially be prevented if all modifiable risk factors were eliminated. Trends of studies in Latin America show, however, that lifestyles are declining. In absence of a cure, prevention is crucial. The aim was to develop a tool that can be used in primary care settings to raise awareness for modifiable risk factors and motivate high‐risk individuals to adopt healthy lifestyles to reduce their risk of dementia.MethodData were from the Cuban (n=1846, mean age=73.9 ±6.4), Dominican Republic (DR, n=1053, mean age=76.3 ±6.8) and Puerto Rican (PR, n=1166, mean age=76.3 ±7.4) cohorts of the 10/66 Dementia Research Group. Participants completed questionnaires, health examination and cognitive tests at baseline and on average 4.5‐5 years later. Logistic regression was used to identify key modifiable risk factors. The 3 or 4 most important modifiable risk factors were combined into a grid and cells were colour coded to display the levels of risk according to absolute proportions of incident dementia (green/low: <9%, yellow/medium: 9‐<13%, orange/high: 13‐<20%, red/very high: >20%).ResultPhysical activity, hypertension and diet were identified as the key modifiable risk factors. Hence, the grid included hypertension (yes/no), diet (composite measure of regular/no fish consumption and <4/4+ serves of vegetables) and physical activity (high, moderate, low) only. The levels of risk varied from low (6.6%) in participants with none of the risk factors to high (18.5%) in participants with all three risk factors. The highest risk was found in participants who were inactive and did not eat fish (24.8%).ConclusionWe have developed a tool that visualises the levels of risk and how each risk factor contributes to the risk of dementia. It also shows how one may lower their risk by addressing the risk factors. The tool can be used in primary care settings to motivate people for adopting healthy behaviours.
Impact of APOE and BDNF Val66Met polymorphisms on spatial navigation and brain morphometry in subjective cognitive decline
Authors: Laczó Jan , Cechova Katerina , Parizkova Martina , Lerch Ondrej , Matoska Vaclav , Kaplan Vojtech , Matuskova Veronika , Markova Hana , Nedelska Zuzana , Vyhnalek Martin , Hort Jakub 
Published: December 2021

AbstractBackgroundThe apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory deficits, less accurate spatial navigation and hippocampal atrophy in nondemented older adults. The brain‐derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment and reduce hippocampal activation in APOE ɛ4 carriers but its role in APOE ɛ4‐related spatial navigation deficits has not been established. We aimed to evaluate the influence of combination of the APOE and BDNF Val66Met polymorphisms on spatial navigation, cognitive functions and volumes of selected brain regions associated with spatial navigation including the hippocampus, entorhinal cortex, precuneus, inferior parietal and posterior cingulate cortex in individuals with subjective cognitive decline (SCD).MethodIn total, 71 older adults with SCD from the Czech Brain Aging Study were stratified based on the APOE and BDNF Val66Met polymorphisms into four groups: ɛ4–/BDNF
Val/Val (n =27), ɛ4–/BDNF
Met (n = 15), ɛ4+/BDNF
Val/Val (n =18), and ɛ4+/BDNF
Met (n=11). The participants underwent comprehensive neuropsychological examination, brain MRI and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real‐space human analogue of the Morris water maze.ResultThe ɛ4+/BDNF
Met group, although similar to other polymorphism groups in age, gender, education, depressive symptoms and global cognitive function, had less accurate allocentric and allocentric delayed navigation performance than the ɛ4–/BDNFVal/Val group (p<0.05). There were no significant differences in egocentric navigation performance, cognitive performance in any cognitive domain including attention and working memory, nonverbal memory, executive function, language and visuospatial function and volumes of selected brain regions associated with spatial navigation between the polymorphism groups (p>0.05).ConclusionIndividuals with SCD and the high risk combination of APOE ɛ4 and BDNF Met alleles had less accurate allocentric spatial navigation than those with the low risk combination of APOE ɛ3 and BDNF Val alleles. This finding may indicate that individuals with SCD and two high risk gene polymorphisms are particularly susceptible to hippocampus‐dependent spatial navigation deficits and may be at greater risk of cognitive decline and progression to mild cognitive impairment. Our results also suggest that spatial navigation testing could more reliably assess the deleterious effect of the BDNF Met allele on cognition than other cognitive tests.
In vivo imaging of LC‐NE Integrity: Mechanism for racial/ethnic disparity in preclinical AD
Authors: Ding Yu‐Shin , Wang Jiacheng , Rusinek Henry , Babb James 
Published: December 2021

AbstractBackgroundDespite studies suggesting that blacks may be at greater risk of developing AD, there have been few studies investigating health disparities, and blacks have been underrepresented in many prominent AD biomarker studies and clinical trials. The current ATN biomarker classification system may not fully account for health disparities and can’t explain the increased prevalence among blacks for both AD and AD vascular risks of diabetes and hypertension when compared to whites. Research on cognitive aging has traditionally focused on how decline in various cortical and hippocampal (Hip) regions influences cognition. However, tau pathology emerges decades before amyloid pathology, appearing first in the brainstem (BS); particularly in the locus coeruleus (LC), the source of brain’s norepinephrine (NE). Our decade‐long studies in humans using a norepinephrine transporter (NET)‐selective radiotracer ([11C]MRB) have demonstrated a special vulnerability of LC to aging and stress.MethodCo‐registration of PET (dynamic [11C]MRB), MRI and the FreeSurfer (FS) atlas images of each individual was used to generate regional time‐activity curves using Firevoxel. Binding potential (BPND) values were determined using MRTM2 with occipital as the reference region. Annual percent change (APC) of BPND was calculated based on linear regression (APC = 100 × (em
– 1), m: slope) and effects of age, gender and ethnicity on tracer binding were evaluated.ResultFor all HC (N=31), with both genders and all races included, age‐sensitive decline of NET availability was observed; e.g., 0.3‐0.5%/yr for Hip, BS and olfactory. However, our data reveals that the decline rate of NET is much faster among blacks starting in the mid‐30s, particularly in black males; e.g., 2‐3%/yr vs. 0.14‐0.23%/yr in thalamus and brainstem for black males vs. white males (p<0.00001).ConclusionIn addition to our previously determined age effect on MRB‐NET binding, this report further reveals the role of ethnicity effects on NET availability. Our study showed that a faster decline of LC‐NE function occurs in blacks, possibly caused by cumulative stress to socioeconomic disadvantage and racial discrimination, and may be responsible for the different disease expression among blacks. Thus, NET availability imaging represents a novel biomarker approach to racial‐dependent strategies for diagnosis and assessment of therapeutic interventions.
Transition to dementia in people with late‐life depression compared to older people with other mental illnesses
Authors: Reppermund Simone , Heintze Theresa , Srasuebkul Preeyaporn , Trollor Julian N 
Published: December 2021

AbstractBackgroundDepression is highly prevalent in dementia and has been reported as a risk factor for dementia. Given the growth of the older population and a potential link between depression and dementia, it is important to understand the health profiles and related service use, especially for possible treatment and prevention strategies. The objectives of this study were to examine the transition to dementia and to compare the health and service use profiles in people with late‐life depression and older people with other mental illness and.MethodA retrospective population‐based study using 13 years of linked health data including 55,717 people aged 65 or older hospitalised with depression and 104,068 people aged 65 or older hospitalised with other mental illness. Logistic regression and cox proportional hazard models were used to analyse the risk of dementia.ResultThe most prominent differences between the two groups were the rates of delirium and self‐harm with a six times lower rate of delirium in people with late‐life depression and an eight times higher rate of self‐harm compared to those with other mental illness. Inpatients with late‐life depression had an increased risk of subsequent dementia by 12% compared to inpatients with other mental illnesses. Besides late‐life depression, only two other conditions, diabetes and cerebrovascular accidents, were associated with an increased risk for dementia.ConclusionInpatients with late‐life depression have an increased risk of dementia compared to older inpatients with other mental illness. Our findings highlight the importance of clinical management and prevention of self‐harm and delirium. The growing ageing population, along with the high prevalence of mental illness and comorbidities in older adults, has significant implications for the planning and equipping of health services to meet the needs of affected individuals.