bluuebunny/crossref_metadata_2025_split huggingface dataset:
Everyday cognition in MCI patients and risk of conversion to Alzheimer’s disease: Evidence from a longitudinal study
Authors: Guinea Sara Fernández , Sánchez Rebeca , Otero Andrea , Marqués Javier González 
Published: December 2021

AbstractBackgroundThe Everyday Cognition scale (ECog) is an informant‐rated questionnaire of cognitive and functional abilities. In recent years, it has been shown to be sensitive for the differentiation of older adults with mild cognitive impairment (MCI) (Farias et al, 2008; Russo et al, 2014), and to the diagnosis of neurodegenerative disease such as Alzheimer’s disease (Farias et al, 2020). However, little is known about its possible utility to predict MCI‐dementia progression in Alzheimer’s clinical syndrome (ACS).Method130 participants (63.8% females), with an average age of 75.27 (SD=5.91), and diagnosed with MCI, were assessed with a comprehensive battery of neuropsychological tests and functional scales, including ECog. In the 2 years follow‐up assessment, 20 participants were diagnosed with ACS. Binary logistic regression and ROC curve statistical analyses were performed.ResultSignificant correlations (p<.05) were found between ECog and neuropsychological tests such as Addenbrooke's Cognitive Examination‐Revised (ACE‐R), Mini‐Mental State Examination (MMSE), a Spanish version of the California Verbal Learning Test (CVLT), the Rey–Osterrieth complex figure test (ROCF) recall, the semantic verbal fluency and the Zoo map. Binary logistic regression results showed that ECog significantly explained the conversion to AD (p<.05). Baseline scores for ECog were significantly higher in participants who developed ACS after two years (p<.05). ROC curve showed a sensitivity of 80% and a specificity of 51% on the optimal cut‐off point (48.5) (AUC=0.69).ConclusionFunctional ability is highly related to cognitive domains. The ECog scale is an useful instrument for the early detection of MCI patients with high risk to develop ACS.
The impact of cerebrovascular disease on blood‐based biomarkers of Alzheimer’s disease
Authors: Laing Krystal K. , Lao Patrick J. , Gutierrez Jose , Sanchez Danurys , Reyes‐Dumeyer Dolly , Lantigua Rafael A. , Honig Lawrence S. , Airey David C. , Manly Jennifer J. , Dage Jeffrey L. , Mayeux Richard , Brickman Adam M. 
Published: December 2021

AbstractBackgroundThe development of ultrasensitive assays for blood‐based biomarkers may allow for detection of Alzheimer’s disease (AD)‐related pathology in large‐scale community‐based cohorts. We previously showed in the Washington Heights Inwood Columbia Aging Project (WHICAP) an association of plasma biomarker concentrations with clinical and pathological AD diagnosis, and that MRI markers of cerebrovascular disease, particularly parietal lobe white matter hyperintensities (WMH), increase the risk and progression of clinical AD. Here, we test the hypothesis that cerebrovascular disease has a direct impact on AD‐related pathology by examining the association of MRI markers of cerebrovascular disease and plasma biomarker concentrations in WHICAP.MethodAmong 300 WHICAP participants with available structural MRI (mean age 81.87+6.45 years, 67% women, 33.3% non‐Hispanic white, 33.3% African American, 33.3% Hispanic, 42% with cognitive impairment) we used SIMOA and MSD technology to measure plasma concentrations of Aβ42, Aβ40, ptau181, ptau217, total tau, and NfL from banked plasma samples. MRI scans were analyzed for regional WMH, presence of infarct, and presence of microbleeds. We first examined bivariate correlations between MRI cerebrovascular measures and plasma biomarker concentrations. For markers that were associated, we conducted demographically adjusted analyses and examined interactions with cognitive diagnostic status.ResultIncreased parietal lobe WMH, specifically, was associated with higher ptau181 (r=0.21, p=0.008) and ptau217 (r=0.13, p=0.05) concentrations. Increased WMH in frontal, temporal, and parietal regions was associated with increased NfL concentrations (rs=0.21‐0.25, ps<0.001‐0.002). Presence of one or more microbleed was associated with increased NfL (r=0.19, p=0.02). In adjusted models the associations of regional WMH with ptau181 and NfL concentrations were independent of and did not interact with diagnosis.ConclusionMarkers of small vessel cerebrovascular disease, particularly parietal lobe WMH, are associated with AD blood‐based biomarkers of phosphorylated tau pathology and neurodegeneration.
Decrease of event related theta power is more profound in patients with Parkinson's disease dementia in comparison to Alzheimer's disease dementia
Authors: Yıldırım Ebru , Gündüz Duygu Hünerli , Hanoğlu Lutfu , Yener Gorsev , Güntekin Bahar 
Published: December 2021

AbstractBackgroundAlzheimer's disease dementia (ADD) and Parkinson's disease dementia (PDD) are the most common types of dementia. ADD and PDD have different pathophysiology and clinical profile. It is important to understand mechanisms underlying pathophysiology, clinical symptoms, and the electrophysiological differences between these two types of dementia. Event‐related theta responses during cognitive paradimgs are one of the essential biomarkers that could succfesully show cognitive decline in dementia patients (Yener et al.,2007;Güntekin et al.,2020). The aim of the present study was to investigate the Event‐related theta responses during the visual cognitive task in patients with PDD and ADD in order to find the differentiation between these two types of dementia.MethodEEG recordings of 15 patients with ADD, 15 patients with PDD, and matched 15 healthy elderly controls (HC) were performed during the visual oddball paradigm. Event‐related phase‐locking and power analysis were performed for theta frequency band (4‐7 Hz). Repeated measures of ANOVA was used for statistical analysis (p<0.05).ResultThere were significant differences among groups for both event‐related theta phase‐locking (p=0.004) and theta power (p<0.0001). ADD (p<0.005) and PDD (p<0.005) groups had reduced theta phase‐locking in comparison to the HC group (Figure 1). Especially, this reduction was more pronounced in the PDD group. In addition, the PDD group had decreased theta power as compared to the HC (p<0.0001) and ADD (p<0.005) group (Figure 1). Figure 1 shows the grand average of event‐related theta power (upper part) and phase‐locking (lower part) and in HC, ADD and PDD groups.ConclusionThe present study showed decreased event‐related theta responses during the visual oddball paradigm in patients with dementia. Especially, PDD patients had the worst event‐related theta responses. These findings could be interpreted as the visual cognitive processes are more impaired in PDD patients compared to ADD patients. References: 1) Yener, G.G., Güntekin, B., Öniz, A., & Başar, E. (2007). Increased frontal phase‐locking of event‐related theta oscillations in Alzheimer patients treated with cholinesterase inhibitors. International Journal of Psychophysiology, 64(1), 46‐52. 2) Güntekin, B., Aktürk, T., Yıldırım, E., Yılmaz, N.H., Hanoğlu, L., & Yener, G. (2020). Abnormalities in auditory and visual cognitive processes are differentiated with theta responses in patients with Parkinson's disease with and without dementia. International Journal of Psychophysiology, 153, 65‐79.
Investigating the associations of trajectories of depressive symptoms and self‐perceived health and incident dementia: An unsupervised machine learning approach
Authors: Klee Matthias , Leist Anja 
Published: December 2021

AbstractBackgroundRisk factors for dementia show inter‐individually varying trajectories over the lifespan. However, risk factors have been mainly investigated with one time‐point assessments. New research suggests that certain risk factor trajectories are associated with increased risk of adverse cognitive outcomes (Demnitz et al., 2020 [https://doi.org/10.1101/2020.05.20.20106963]; Singh‐Manoux et al., 2018 [https://doi.org/10.1016/j.jalz.2017.06.2637]). However, it remains unclear how sequential and simultaneous changes of risk factors alter the individual risk for developing dementia. Testing the joint contribution of trajectories of depressive symptoms and self‐perceived health on incidence of dementia, we hypothesized that consistently poor as well as deteriorating trajectories increase the risk for incident dementia, and explored possible interactions of the trajectories.MethodA total of 5,326 respondents to the SHARE survey, mean age 73.9 years, and 6 complete follow‐ups spanning ∼13 years, answered the EURO‐D depression scale, self‐perceived health (SPH) (t1‐t5), and self‐reported dementia diagnosis at last follow‐up (t6). To investigate the predictive ability of distinct longitudinal trajectories, we applied unsupervised statistical learning methods (K‐means cluster modelling). Clusters indicated distinct risk factor trajectories, which were used as exposures in stepwise logistic regressions to predict incident dementia, controlling for age, gender, education, and country.ResultCluster analysis revealed five distinct trajectories each for SPH and EURO‐D, with varying dementia incidence. In stepwise logistic regressions, respondents with trajectories “consistently poor health” and “consistently high depression” showed elevated risk of dementia (OR = 4.02 [1.39, 14.75] and OR = 2.26 [1.03, 4.95], respectively) compared to the combined baseline risk for “consistently low depression” and “consistently good health”. Interactions were not significant. However, respondents with the combination of “consistently high depression” and “consistently poor health” showed increased risk (N = 246; 6.1% dementia).ConclusionApplying unsupervised machine learning is helpful to incorporate longitudinal information on depressive symptoms and self‐perceived health and model these risk factors longitudinally to test their contribution to explain incidence of dementia. The predictive ability of the trajectories of depressive symptoms and self‐perceived health for dementia indicates the potential for improving the identification of people at risk for developing dementia in late life by exploiting trajectory information readily accessible through regular medical check‐ups in old age.
Identifying and characterizing patterns of functional decline in memory clinic patients
Authors: Dubbelman Mark A. , Caelers Michael , van der Flier Wiesje M , Scheltens Philip , Sikkes Sietske A.M. 
Published: December 2021

AbstractBackgroundAlzheimer’s disease and related disorders (ADRD) are characterized by progressive cognitive and functional decline. To improve prognosis, it is important to predict the expected rate of functional decline. In the current study, we sought to uncover patterns of changes in everyday functioning among memory clinic patients, and to explore factors associated with said groups.MethodMemory clinic patients (N=573, 64.7±7.9 years old, 39% female) underwent extensive dementia screening at baseline, and were followed over time (median 1.0 years, range 0.3–6.2 years, N observations=1632). Diagnoses included subjective cognitive decline, mild cognitive impairment, and dementia with varying etiologies. We measured everyday functioning with the Amsterdam Instrumental Activities of Daily Living Questionnaire (A‐IADL‐Q). Longitudinal latent class analysis (LLCA) was used to identify groups of patients based on their rate of change in IADL, including non‐linear trajectories. We subsequently used random forests to explore the associations between the LLCA groups and demographics, neuropsychological test performance, and magnetic resonance imaging rating scales for medial temporal and global atrophy.ResultWe identified six groups: two stable (high and average), three declining (slow, moderate, and fast), and one improving group (see Table 1, Figure 1). All groups differed in baseline A‐IADL‐Q scores, with the declining groups having lower scores. The fast declining group consisted mostly of dementia patients, whereas the high stable group consisted mostly of patients with subjective cognitive decline. The area under the curve of the random forest classification was .95, thus accurately assigning patients to the correct group based on baseline characteristics. The following variables contributed most to the classification of the groups: baseline A‐IADL‐Q score (mean decrease accuracy [MDA]=200.5), a visuospatial task (copy of Rey Complex Figure, MDA=36.6) and a processing speed task (Letter Digit Substitution Task, MDA=18.5). Atrophy rating scales contributed less.ConclusionDifferent trajectories of functional decline were distinguished, and associated with baseline levels of cognitive and daily functioning. Our findings suggest that neuropsychological assessment may provide additional information on future changes in daily functioning. These findings may contribute to a more accurate prognosis of future functional decline, and by extension, future care needs.
Dementia policy and its implication for supporting people with ADRD during the unprecedented time in China
Authors: Wang Huali 
Published: December 2021

AbstractBackgroundImproving dementia care has been prioritized in a community‐based psychosocial support system in China. In 2020, the National Health Commission announced implementing the National Dementia Strategic Plan in more than 60 demonstration areas. The Plan intends to improve community‐based dementia care by utilizing the existing psychosocial support system, creating multidisciplinary teams, and establishing a collaborative network between specialists and primary care services. During the COVID‐19 pandemic, community service has played a pivotal role in supporting residents, especially older adults. Therefore, the study aimed to explore the implications of the National dementia strategic plan in supporting persons living with dementia during the unprecedented time.MethodWe conducted qualitative interviews with ten leaders of community health centers. All the interviews were audio‐recorded and transcribed. Thematic extraction was used for data analysis.ResultThis presentation will report the main findings of the qualitative studies, including the potential of integrating the Dementia strategic plan with community service during the unprecedented times, the barriers and enablers for the implementation, and the interaction between the Plan and the managerial regulations relevant to preventing the cross‐infection of COVID‐19.ConclusionCommunity service is mainstream both for COVID‐19 prevention and dementia care. There is a great potential to integrate the national dementia strategic plan with the community psychosocial support tackling the disaster response during the unprecedented time.
Electrophysiological differences between older women and men in the absence of disease: A step closer to personalized medicine
Authors: de Frutos Jaisalmer , Cuesta Pablo , Fernández Ricardo Bruña , Vilca Brenda Chino , Torres Lucia , Arrazola Juan , Higes Ramón López , Dolado Alberto Marcos , Maestú Fernando 
Published: December 2021

AbstractBackgroundMultiple electrophysiological footprints have been identified to be associated with silent and clinical neuropathological processes predicting mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Nevertheless, it is important to bear in mind that women show greater risk of developing both MCI and AD. Therefore, it is crucial to understand in first place how sex differences might modulate these electrophysiological mechanisms in healthy older adults.Method240 healthy cognitively normal older adults (age = 60 ‐ 85) participated in this study. They were divided into two groups: women (n = 140) and men (n = 120), matched in age and educational level. Each individual underwent four minutes of closed eyes resting state MEG recording. The aim was to detect any clusters where power was significantly associated with sex and also any networks where functional connectivity was associated with sex (total intracranial volume and age where used as covariates p‐value < 0.01) in either frequency band (gamma, beta, alpha, theta and delta).ResultWomen showed greater power in the beta band in a posterior cluster composed of occipital and temporal brain regions. Additionally women also showed greater functional connectivity across all frequency bands, always in frontal brain networks.ConclusionEven in the absence of an undergoing neuropathological process, men and women present differential patterns of brain connectivity and power. The role that these differences play in the pathogenesis of Alzheimer’s disease remains to be fully understood. However, these differential baseline characteristics should be accounted for in studies aiming to establish electrophysiological markers of AD.
A multimodal study on the effect of sex on Alzheimer's disease clinical and biomarker changes in adults with Down syndrome
Authors: Iulita M. Florencia , Bejanin Alexandre , Vilaplana Eduard , Carmona‐Iragui Maria , Benejam Bessy , Videla Laura , Barroeta Isabel , Fernandez Susana , Altuna Miren , Pegueroles Jordi , Montal Victor , Valldeneu Sílvia , Giménez Sandra , González‐Ortiz Sofía , Muñoz Laia , Padilla Concepción , Aranha Mateus Rozalem , Estellés Teresa , Illán‐Gala Ignacio , Belbin Olivia , Tamayo Natalia Valle , Camacho Valle , Wilson Liam , Annus Tiina , Osorio Ricardo , Videla Sebastián , Lehmann Sylvain , Holland Anthony J , Zetterberg Henrik , Blennow Kaj , Alcolea Daniel , Clarimón Jordi , Zaman Shahid , Blesa Rafael , Lleó Alberto , Fortea Juan 
Published: December 2021

AbstractBackgroundThe study of sex differences in Alzheimer's disease (AD) is gaining increasing attention. Yet, few studies have examined the effect of sex in genetically determined forms of AD. Here, we explored the impact of sex on AD‐related clinical and biomarker changes in a population‐based cohort of adults with Down syndrome, who have a lifetime risk of over 90% to develop AD.MethodThis is a cross‐sectional study of 549 adults with Down syndrome. We compared AD prevalence, as well as cognitive and AD biomarker changes, in relation to age and sex in the whole cohort. Participants underwent neuropsychological examination with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG‐DS) and modified cued recall test (mCRT). Most also had at least one biomarker assessment of amyloid pathology (CSF Aβ42, Aβ42/40 ratio and amyloid‐PET), tau (CSF and plasma p‐Tau‐181) and neurodegeneration (CSF and plasma NfL, FDG‐PET and 3T structural MRI). We used within‐group locally estimated scatterplot smoothing (LOESS) models to compare the trajectory of biomarker changes with age in women versus men, as well as the interaction with the APOE ε4 allele.ResultThe prevalence of AD across five‐year age intervals and the mean age at AD diagnosis was similar between men and women. Men and women had similar trajectories in CAMCOG scores with age, but men showed lower mCRT scores from age 45 years. There were no differences between men and women in the CSF Aβ42/40 ratio or amyloid‐PET, or in the trajectories of tau and neurodegeneration biomarkers. When considering the APOE genotype, women carrying the ε4 allele showed an earlier age at AD diagnosis and higher prevalence of symptomatic AD between ages 40‐45 compared to non‐carriers. The female advantage on mCRT scores was lost in women carrying an ε4 allele.ConclusionSex did not have a main effect on AD risk or biomarker changes. However, APOE ε4 modified the age at symptomatic AD diagnosis and age‐related mCRT scores in women, but not in men. These results emphasize the complexity of the relationship between biological sex and AD, and the need to further explore interactions with APOE ε4.
CSF tau phosphorylation occupancy at t217 increases in MAPT R406W mutation carriers without amyloid pathology
Authors: Sato Chihiro , Mallipeddi Nipun , Ghoshal Nupur , Wright Brenton A. , Day Gregory S. , Davis Albert A. , Kim Albert H. , Zipfel Gregory J. , Bateman Randall J. , Gabelle Audrey , Barthelemy Nicolas R. 
Published: December 2021

AbstractBackgroundTau hyperphosphorylation at Threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer disease (AD). However, it remains unclear whether pT217 could be modified in other tauopathies. Using immunoprecipitation and mass spectrometry, we compared CSF T217 phosphorylation occupancy (pT217/T217) and amyloid beta (Aβ) 42/40 ratio in cognitively normal controls, and individuals with AD, Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), and sporadic and familial Frontotemporal Dementia (FTD).MethodCSF Aβ, tau and phosphorylated tau (p‐tau) were measured using immunoprecipitation and quantitative mass spectrometry methods. Amyloid and tau Positron Emission Topography (PET) imaging were measured in a subset of participants and analyzed for correlation. Quadrant analyses were performed to assess amyloid and p‐tau positivity.ResultWe confirmed the strong association between CSF Aβ 42/40 and pT217 measures in most samples. Individuals with AD had high CSF pT217/T217 and low Aβ 42/40. In contrast, controls and the majority of patients with other tauopathies had low CSF pT217/T217 and normal Aβ 42/40. We identified a subgroup of individuals with increased CSF pT217/T217 and normal Aβ 42/40 ratio relative to controls. Most of these individuals were identified as MAPT R406W mutation carriers, a tau mutation leading to 3R+4R tauopathy similar to AD but without amyloid pathology. Diagnostic accuracies of CSF Aβ 42/40 alone, CSF pT217/T217 alone, and combination of both biomarkers were examined. We show that combination of both biomarkers can separate MAPT R406W carriers from control (AUC=0.960) and other tauopathies that are primarily 4R tauopathies (AUC=0.934).ConclusionWe demonstrate the importance of measuring both CSF Aβ 42/40 and pT217/T217 to improve AD diagnosis and differentiate MAPT R406W mutation carriers. This supports that changes in CSF pT217/T217 ratio is not a specific biomarker for AD but reflects common downstream tau pathology in these two 3R+4R tauopathies.