bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease: Relation with disease stage, sex, and daily function impairment
Authors: Zhang Wenbo , Lü Yang , Yu Weihua 
Published: June 2023

AbstractBackgroundTo reveal the relations between neuropsychiatric symptoms (NPS), stages of cognitive impairment, sex, and daily function impairment in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).Method1,154 patients with MCI and AD were enrolled from 2014 to 2021 from the Memory Clinic, The First Affiliated Hospital of Chongqing Medical University. Mini‐mental State Examination (MMSE) was used to assess the cognitive function, and Clinical dementia rating scale (CDR) was used to evaluate the disease severity of patients. NPS and function of patients’ daily life were evaluated by Neuropsychiatric Inventory (NPI) and activities of daily living (ADL) respectively.ResultPsychosis symptoms displayed the highest prevalence in MCI (43.3%) and mild AD stage (62.2%), while in moderate and severe AD, behavior symptoms showed its dominance (86.7% and 96.4%, respectively). Delusion, apathy, AMB and sleep disturbance were the discriminant symptoms across the spectrum of cognitive decline (all P <0.05). Depression was more prominent in female (26.1% vs. 14.9% in MCI; 40.2% vs. 21.0% in AD, all P< 0.05) while male patients presented higher prevalence in apathy (27.0% vs. 18.6% in MCI; 54.1% vs. 42.8% in AD, all P< 0.05). Physical self‐maintenance was negatively impacted by apathy and sleep disturbance at mild AD stage, while instrumental activity of daily living was significantly influenced by aberrant motor behavior in MCI and mild AD (all P< 0.05).ConclusionThe prevalence of NPS is correlated with sex, the stage of cognitive impairment and daily living function. Revealing their relations can allow he development of better prevention and treatment strategies for patients with cognitive impairment.
European adaptation of the Harmonized Cognitive Assessment Protocol: Methodological lessons learned from SHARE‐HCAP
Authors: Otero Marcela , Douhou Salima , Pettinicchi Yuri , Sommer Elena , Ludmark Vania Panes , Rieckmann Anna , Börsch‐Supan Axel 
Published: June 2023

AbstractBackgroundAlzheimer’s disease and related dementias pose a major epidemiological challenge worldwide. A key impediment to dementia research is the availability of internationally comparable cognitive assessments that are socio‐culturally adapted and language appropriate. The Survey of Health, Ageing and Retirement in Europe‐ Harmonized Cognitive Assessment Protocol (SHARE‐HCAP) study aims to use multistage translation and pre‐statistical harmonization procedures to develop an in‐depth neuropsychological battery that assesses cognition in a population‐based survey administered across Continental Europe.MethodSHARE‐HCAP will assess cognitive functioning using the HCAP – an hour‐long neuropsychological test battery and informant interview developed for the Health and Retirement Study and similar population‐based ageing surveys. The survey will be implemented in five European countries (Czech Republic, Denmark, France, Germany, Italy) in a stratified study sample of 2,500 SHARE panel respondents. SHARE‐HCAP’s adaptation procedures include the a) development of socio‐culturally appropriate recruitment strategies and interview techniques, b) translation of HCAP content, including study documents, test materials, and informant interview by a team of multi‐lingual researchers and clinicians, c) pre‐statistical harmonization of the HCAP test battery, including administration and scoring, and d) development of comprehensive training of local survey interviewers who were inexperienced in cognitive assessment. SHARE‐HCAP adaptations were assessed in two small‐scale preliminary data collections. Descriptive statistical analyses of neuropsychological test scores were conducted.ResultTo date, we have developed lingo‐culturally adapted HCAP documents (e.g., informed consent, recruitment materials), and neuropsychological test content and interviews for five SHARE countries. Descriptive statistics suggest that SHARE‐HCAP pre‐test data behave similarly to neuropsychological test data of two English‐language HCAP studies (i.e., USA and England).ConclusionAs the first HCAP sub‐study conducted cross‐nationally, SHARE‐HCAP’s cultural and linguistic adaptations can provide valuable insights into the collection of cognitive health data in population‐based surveys in multi‐national contexts. Preliminary results support the comparability of SHARE‐HCAP to English‐language HCAP batteries. Assessing cognitive functioning in population studies, such as SHARE‐HCAP, leverages the international variation of health and life circumstances to identify the bio‐medical and socio‐economic conditions that contribute to cognitive health over the life‐course.
The effect of education on ATN biomarkers of Alzheimer’s disease according to the presence of APOE4
Authors: Kim Yeshin , Jang Hyemin , Jang Jae‐Won 
Published: June 2023

AbstractBackgroundAs a proxy of cognitive reserve, education is known to have a protective effect against the cognitive decline in Alzheimer’s disease. It is explained that those who have higher education would resist pathologic burdens through other mechanisms such as changes of functional networks of the brain. However, it is not well known whether there is an association between education and the pathologic burden. APOE is the important genetic risk factor, and the presence of the ε4 allele is associated with biomarkers. This study aimed to evaluate the association between education and ATN biomarkers in Alzheimer’s disease according to the presence of APOE4.MethodWe analyzed 1,076 Alzheimer’s Disease Neuroimaging Initiative participants’ data (336 cognitively normal (CN), 279 early aMCI, 279 late aMCI, 182 AD). The values of CSF amyloid β1‐42, CSF phosphorylated Tau (p‐Tau), and 18F‐fluorodeoxyglucose‐positron emission tomography (FDG PET) brain metabolism were used as ATN biomarkers. We analyzed the association between education and ATN biomarkers in each group, according to the presence of APOE ε4 allele, using a multiple linear regression model after controlling age and sex.ResultHigher education was related to lower CSF p‐Tau in the early aMCI group only when APOE4 was positive (β = ‐1.3, p = 0.013). Other than the early aMCI group, we could not find any association between education and ATN biomarkers.ConclusionThis finding suggests that education could have a protective effect on the pathologic tau burden in the presence of APOE4, especially at the early aMCI stage.
Head‐to‐head comparison of Relative Cerebral Blood Flow derived from [18F]florbetapir and [18F]flortaucipir in subjects with Subjective Cognitive Decline
Authors: Tuncel Hayel , Visser Denise , Timmers Tessa , Wolters Emma E , Ossenkoppele Rik , van der Flier Wiesje M. , van Berckel Bart N.M. , Boellaard Ronald , Golla Sandeep S.V. 
Published: June 2023

AbstractBackgroundSeveral studies validated R1 as a marker for relative cerebral blood flow (rCBF). However, the similarities or differences of R1 estimates obtained from different PET tracers has never been investigated.AimThe aim of the current study was head‐to‐head comparison of R1 estimates, derived from dynamic [18F]florbetapir and [18F]flortaucipir PET scans.MethodFifty subjects with subjective cognitive decline (Aβ‐;N = 31, Aβ+;N = 19) underwent both [18F]florbetapir and [18F]flortaucipir PET (interval: 50.6 ± 34.7 days). Receptor parametric mapping (RPM) was used to generate R1 maps with cerebellar grey matter as reference. For voxel‐wise analyses, Statistical Parametric Mapping software (SPM12) was used. Furthermore, different regions‐of‐interest were assessed (in subject‐space). Paired t‐tests, coefficients of determination (r2) and ICC were used to compare R1 estimates from [18F]florbetapir and [18F]flortaucipir PET.ResultsVoxel‐wise analysis revealed only a few small significant clusters in part of the thalamus, insular gyri, midbrain and part of the cerebellum with higher R1 estimates for [18F]florbetapir and higher R1 estimates in the hippocampus, vermis, midbrain and calcarine sulcus for [18F]flortaucipir in Aβ‐ subjects (Figure 1a & 1b). In Aβ+ subjects, [18F]florbetapir showed higher R1 estimates only in part of the thalamus and [18F]flortaucipir showed higher R1 estimates in the hippocampus and striatum (Figure 1c & 1d). Despite the small amount of significant voxels, [18F]florbetapir R1 showed good correlation and excellent ICC with [18F]flortaucipir for whole brain (Aβ‐:r2 = 0.76, ICC:0.92; Aβ+:r2 = 0.60,ICC = 0.87).ConclusionTo conclude, [18F]flortaucipir and [18F]florbetapir showed similar R1 estimates in cortical regions, illustrating that R1 is a robust marker for flow independent of tracer of interest.
The QSP model of TREM2 influences on inflammatory state of microglia in Alzheimer’s disease
Authors: Lerner Stepan , Karelina Tatiana 
Published: June 2023

AbstractBackgroundInflammation is one of the critical components in the development of neurodegenerative diseases. Microglia is the resident of macrophages of the central nervous system. In the AD brain, microglial cells are found in close association with amyloid beta deposits. Histological examination of AD brains as well as cell culture studies have shown that the interaction of microglia with fibrillar amyloid beta leads to their phenotypic activation. It increases the activation of microglia cells and switches them from resting (M0) to activating (M1 or M2) state and the release of cytokines. The role of microglia in AD progression is unclear with conflicting reports regarding their detrimental or protective contribution to the disease. The QSP model was developed to investigate influence of TREM2 on inflammation of microglia.MethodsThe model describes microglia resting state, phagocytosis, TLR, P2×7 and TREM2 receptors, kinases, intracellular signaling pathways, apoptosis of microglia cells, response of microglia to LPS, oligomeric and fibrillar amyloid and cytokines (IL6, IL1b, TNFa), distribution of cytokines from the brain into cerebrospinal fluid and blood.ResultsThe model correctly describes decreased phagocytosis, increased cytokine and pro‐inflammation factors with influence of amyloid beta and TREM2 KO during LPS‐induction. It demonstrates that: 1) TREM KO leads to decrease of phagocytosis [1] 2) Ab influence on TREM2 leads to increase of inflammatory cytokine level [2] 3) Inhibitor of PI3K (LY294002) decreases phagocytosis in signaling pathway (PI3K/FoxO/phagocytosis) [3].ConclusionsThis QSP model can be used to predict the response of microglia to various conditions caused by neurodegenerative diseases and therapies targeting microglial state.[1] – PMID: 30548312[2] – PMID: 33065553[3] – PMID: 28842601
Photobiomodulation in human neuroblastoma under oxidative stress
Authors: Rossato Rafaella Carvalho , Salles Geisa Rodrigues , de Albuquerque Amanda Lira Gurgel , Pacheco‐Soares Cristina 
Published: June 2023

AbstractBackgroundWith the increase in life expectancy, the number of people with neurodegenerative diseases such as Alzheimer’s Disease (AD) is rising rapidly. Considering the pathways of AD, one of its fundamental processes is oxidative stress, affecting the central nervous system and cell regeneration. Interestingly, in the last decades, photobiomodulation has shown positive effects on neural cells that are compromised by AD. Studies have demonstrated that LED (light emitting diode) irradiation regulates cell function, stimulating cell proliferation, promoting biomodulation in the cytoskeleton, and reducing apoptosis. To contribute with the elucidation of the importance of photobiomodulation in AD, this study aims to evaluate its neuroprotective effect, comparing different energy density of LED irradiating in SH‐SY5Y cells (human neuroblastoma) under the effect of oxidative stress induced by hydrogen peroxide (H2O2).MethodSH‐SY5Y cells (human neuroblastoma) were cultivated in DMEM/F12 medium (Dulbecco’s modified Eagles medium ‐ Gibco), supplemented with 10% fetal bovine serum and 1% antibiotic and antimycotic, at 37°C, in an atmosphere of 5% CO2. Cells were plated in 24‐well plates. After cell adhesion, cells were irradiated with LED at 660 nm (LED Biopdi/Irrad‐Led5), at energy densities of 1 J/cm2, 3 J/cm2, 5 J/cm2 and 10 J/ cm2. 24 h after irradiation, oxidative stress was induced with 200 μM H2O2 for 24h (this parameter had been previously determined by ROSSATO, R. C. et al, 2021).ResultOnce cells are irradiated and stressed, a considerable statistic difference is observed for all energy densities evaluated, compared to the stressed‐only group (H2O2). Importantly, the energy density of 3 J/cm2 was the lowest one that obtained better statistical increase in mithocondrial activity (p < 0.0001).ConclusionIt was possible to determine and compare the energy densities of LED irradiation to promote cellular photobiomodulation, inducing mithocondrial activity on neubroblastoma. Importantly, this study demonstrated the neuroprotective effect of LED in an in vitro model of AD oxidative stress, approaching novel concepts and a preventive tool.ROSSATO, R. C. et al. Neuroprotective effects of taurine on SH‐SY5Y cells under hydrocortisone induced stress.
Research, Society and Development, v. 10, n. 9, p. e55510918426‐e55510918426, 2021
Review of assessment methods for dementia
Authors: Parsapoor Mahboobeh , Menard Pierre‐Andre , Boulianne Gilles 
Published: June 2023

AbstractBackgroundMore than 50 million people worldwide live with various types of dementia, which incorporates a progressive decline in patients' cognition. Early detection of dementia in older adults is crucial and helps them apply for intervention programs. Numerous assessment methods have been developed to be used in clinical practice and help clinicians accurately detect dementia and diagnose its types. The recent advancement in the artificial intelligence domain has revolutionized the early detection of dementia and allowed clinicians to use AI‐based assessment technologies for detecting dementia at its very mild decline stage. The AI community aims to develop valid, efficient, practical, reliable, and accurate AI‐based assessment technologies to detect dementia; thus, to help the community, this paper reviews clinical assessment methods and recently developed AI‐based assessment technologies, particularly AI‐based language and speech assessment techniques. Moreover, it collects information about available datasets, python libraries for developing AI assessment methodologies to detect dementia.MethodWe have extracted around 300 peer‐reviewed articles from PubMed and MEDLINE related to AI‐based assessment technologies (i.e., focusing on automated language and speech‐based assessment methods) and cognitive, behavioral, neurophysiological, functional assessment methods.ResultBy reviewing more than 50 various clinical and AI assessment methods, we listed the advantages and limitations of clinical and AI assessment methods and available machine learning datasets, python scripts, and libraries to develop AI assessment methods to detect dementia.ConclusionThe paper could provide valuable information for the AI community to have better progress in developing quick, accurate, multicultural, practical assessment technologies with high specificity and sensitivity. The paper can be beneficial for mental health clinicians to learn about known AI‐based assessment methods to detect dementia.
Autopsy‐confirmed minimally invasive biomarker identifies Alzheimer’s Disease even in the presence of co‐morbid pathologies
Authors: Chirila Florin , Xu Guang , Fontaine Daniel , MacTurk William , Khan Tapan , Alkon Daniel L 
Published: June 2023

AbstractBackgroundThere are currently no FDA‐approved tests that are highly sensitive and highly specific for Alzheimer’s disease (AD). Diagnostic Accuracy has been even more difficult due to recent findings that >50% of AD brains show co‐morbid pathologies such as multi‐infarct dementia and Frontal Lobe Dementia. Here, we describe an autopsy‐confirmed AD Biomarker that identifies AD pathology even with co‐morbid brain pathology.MethodA Morphometric Imaging (MI) assay was previously shown to correlate the dementia and presence of AD pathology in the brains of AD patients (Chirila et al., 2013) with abnormalities of skin fibroblasts isolated with routine punch biopsies (∼3mm). Cells were cultured on a thick layer of 3‐D Matrigel matrix and subjected to image analysis. AD cell lines formed large aggregates in contrast to non‐AD dementia (non‐ADD) or non‐demented control (NDC) cell samples. Typically skin fibroblasts formed “networks” analogous to networks formed by neurons isolated in cell culture and AD networks were slower and less connected Quantitative image analyses enabled the calculation of average unit aggregate area (A) in terms of ln(A/N). Samples were collected with a double‐blind protocol for demented patients > 55 years old who eventually reached blinded autopsy examination. NDC samples were collected for Biomarker assay only.ResultThe total fibroblast patient sample (N = 74) consisted of AD (N = 26) patients and non‐ADD (N = 21) patients (all were autopsy confirmed and had blinded biomarker data); and NDC, N = 27 that had biomarker data. The cut‐off value of ln(A/N) = 6.98 was determined from the biomarker values for NDC patient samples. For the Biomarker AD vs. Non‐ADD data, True Positive = 26, False Negative = 0, False Positive = 0, with Sensitivity and Specificity calculated as 100 and 100, respectively. (AD vs. Non‐ADD, p < .000001). The NDC MI assay values closely superimposed with the non‐ADD sample values.ConclusionIn these autopsy‐confirmed results, the MI Biomarker distinguished AD from Non‐ADD patients and correctly diagnosed AD even in the presence of other co‐morbid pathologies at autopsy. This highly, accurate, minimally invasive AD biomarker, therefore, was validated by rigorous reference to the NIH gold standard criteria for an AD Diagnosis, dementia in life and the presence of plaques and hyperphosphorylated tau at autopsy.
Implementing and evaluating the driving and dementia roadmap (DDR) during the COVID pandemic
Authors: Naglie Gary , Stasiulis Elaine , Sandhu Harvir , Gallucci Christina E. , Rapoport Mark J. 
Published: June 2023

AbstractBackgroundTo address the gap in evidence‐based interventions and resources to support people living with dementia (PWD) and family/friend carers (FCs) through the challenging process of driving cessation, we developed a web‐based educational resource called the Driving and Dementia Roadmap (DDR). An implementation evaluation, which took place during the COVID pandemic, was conducted to explore the delivery, acceptability, adaptability, preliminary benefits and limitations of the DDR.MethodThe DDR was delivered to Alzheimer Society (AS) clients by staff from six organizations in four Canadian provinces from December 2020 to September 2021. Semi‐structured interviews were conducted with 19 AS staff, eight PWD and 13 FCs. In addition to questions about their experiences of delivering and using the DDR, participants were asked about the impact of COVID on using the DDR. Data were examined using a thematic analysis approach.ResultAS staff reported that client concerns about driving cessation and the need for the DDR were less than anticipated due to COVID. They attributed this to other pressing issues such as the need to stay safe from COVID, a lack of access to services and activities, caregiver burnout and PWD’s isolation. FCs and PWD also indicated that driving was not an immediate concern because they were driving less in the pandemic. However, AS staff expressed apprehensions about increased driving risk in the aftermath of COVID due to reports of PWD’s profound cognitive decline and lack of driving experience during the pandemic.ConclusionAlthough COVID’s impact on driving cessation initially lessened PWD’s and FCs’ urgency in attending to this issue, the longer‐term implications of neglecting this issue may be considerable for PWD and FC. The need for resources, such as the DDR, to support PWD and FCs in the decision‐making and transition to non‐driving will be particularly critical post‐COVID.
Association of HbA1c trajectory and variability with cognitive function
Authors: Mongraw‐Chaffin Morgana , Evans Joni K , Bancks Michael P. , Schaich Christopher L. , Shappell Heather M , Espeland Mark A. , Hayden Kathleen M. 
Published: June 2023

AbstractBackgroundType 2 diabetes (T2D) is an important modifiable risk factor for cognitive decline, and increasing evidence suggests that worse glucose control, in addition to a diagnosis of T2D, may play a role in cognitive function in later life. Despite this increasing concern, evidence regarding the relative contributions of poor glucose control and higher glucose variability to cognitive dysfunction among individuals with overweight or obesity is limited, mostly due to lack of repeated measures in many studies.MethodLook AHEAD MIND Study participants, aged 45‐76 years at baseline (2001‐04) with T2D and overweight or obesity, were randomized to an intensive lifestyle intervention focused on weight loss or a diabetes support and education condition, which were discontinued after ∼10 years. HbA1c levels were evaluated at years 1‐4, 6, 8, and 10. Cognitive function was evaluated up to four times between years 8‐18 with a cognitive battery that assessed memory, attention, and executive function domains. Cognitive scores were binned into four groups based on relative timing of cognitive assessments (8‐9; 10‐11; 12‐14; and 15‐18 years). We classified HbA1c variability according to: Variability Independent of the Mean (VIM), Average Real Variability (ARV), and data‐driven latent trajectories. Mixed linear regression models for standardized composite cognitive scores were adjusted for: repeated measures, order of cognitive test, years from randomization, randomization arm, age, sex, race/ethnicity, years of education, CVD history, and APOE ε4.ResultFour HbA1c trajectories were identified: increasing, decreasing, stable‐high, and stable‐low. Composite cognitive scores were significantly lower for increasing, decreasing, and stable‐high HbA1c trajectories ‐compared to stable‐low HbA1c (Table). In multivariable analysis, higher baseline HbA1c, ARV, and VIM were associated with lower composite cognitive scores, and differences between groups were similar by years since randomization. Estimates for ARV and VIM were attenuated when adjusted for baseline HbA1c (not shown). Estimates were similar for tests from all cognitive domains, with little heterogeneity by randomization arm.ConclusionAmong individuals with T2D, higher HbA1c at baseline and greater HbA1c variability over 10 years were significantly associated with lower cognitive scores, suggesting that maintaining glucose control may be useful for the prevention of cognitive decline.