bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Predictive Value of Structural OCT in Preclinical AD
Authors: Alber Jessica 
Published: January 2025

AbstractBackgroundResearch shows that structural retinal changes, measured via spectral‐domain optical coherence tomography (SD‐OCT), are sensitive diagnostic biomarkers in AD. Our recent work aims to validate retinal biomarkers as risk biomarkers in preclinical AD. We compared retinal layer thickness to plasma ptau217 (a valid measure of Aβ pathophysiology in preclinical AD) to determine the predictive value of structural retinal changes in preclinical AD.MethodA total of 120 cognitively unimpaired (CU; CDR=0, MoCA>26) older adults aged 55‐80 underwent SD‐OCT imaging. Plasma samples were analyzed with the Simoa ALZpath pTau 217 assay. Multinomial logistic regression models, with age, APOE E4 status and first degree family history as covariates, were used to assess the predictive value of each retinal layer on plasma ptau217 concentrations, with emphasis on layers that have shown thinning in clinical AD (macular retinal nerve fiber layer, mRNFL; ganglion cell layer, GCL; inner plexiform layer, IPL). Additional iterative models added mRNFL, then GCL and IPL, to assess the combined predictive value of the retinal layers. ROC analysis with assay‐specific plasma ptau217 cut‐off .495 was used to determine how well each retinal layer and/or the retinal layers combined predicted preclinical AD status. Partial correlations (controlling for age) were performed to determine the relationships between individual retinal layer thicknesses and plasma ptau217.ResultThere were significant positive correlations between the thickness of the inner inferior and superior GCL and IPL and plasma ptau217 (all p<.05). Inner inferior and superior mRNFL and GCL thickness were significant predictors of plasma ptau217. The model that had the best performance included age, APOE status, first degree family history, and the inner inferior and superior thickness of the mRNFL, GCL, and IPL, with AUC = .90, (95%CI = .86‐.93, p<.01).ConclusionRetinal thickness, measured by SD‐OCT, could be a useful screening tool to identify those at high risk for preclinical AD who may benefit from more invasive or expensive neuroimaging for confirmation. Longitudinal follow‐up is ongoing to determine the prognostic value of SD‐OCT in predicting conversion to symptomatic AD.
Plasma ptau181 levels at baseline and over time according to amyloid status and SCD in SILCODE cognitively unimpaired older adults
Authors: Shao Kai , Kuhn Elizabeth , Hu Xiaochen , Yan Shaozhen , Chen Zhigeng , He Beiqi , Jiang Xueyan , Li Ruixian , Wang Xuanqian , Wei Min , Wei Yongzhe , Yang Jie , Yu Xianfeng , Zhang Mingkai , Zhang Liang , Lu Jie , Wagner Michael , Han Ying ,   SILCODE study group
Published: January 2025

AbstractBackgroundCognitively unimpaired (CU) older adults with abnormal levels of β‐amyloid (Aβ) deposition are considered in the preclinical stage of Alzheimer’s disease (AD) and, when combined with the subjective cognitive decline (SCD), are proposed as the stage 2 AD in the NIA‐AA framework. Here, we aim to investigate whether neuropathologic deterioration increases in early stages, particularly in stage 2 AD.MethodWe included 341 CU participants over 50 years of age from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. SCD was defined based on baseline cognitive complaints with associated concern/worry, whereas normal control (NC) did not express any concern/worry. Aβ status was defined based on amyloid‐PET or, if not available, on plasma Aβ42/40 ratio. All selected participants had available plasma phospho‐tau181 (ptau181), and were divided into four groups according to SCD combined with baseline Aβ positivity. General linear models and linear mixed‐effect models were performed to determine whether ptau181 levels differed between groups (i.e., NC.Aβ‐, SCD.Aβ‐, NC.Aβ+, SCD.Aβ+) at baseline and over time.ResultAt baseline, the four groups were significantly different in terms of ptau181 levels (p=0.001), with the SCD.Aβ+ group having higher levels than NC.Aβ‐ (p=0.004) and SCD.Aβ‐ (p=0.003), but not different from NC.Aβ+ (p=0.63). In the smallest sample of 81 CU with available follow‐up for ptau181 (i.e., 15 NC.Aβ‐, 35 SCD.Aβ‐, 8 NC.Aβ+, 23 SCD.Aβ+), we replicated the baseline differences (p=0.037). Longitudinal analysis showed that ptau181 levels changed differently between groups over time (p=0.016), with SCD.Aβ+ showing a faster increase over time than SCD.Aβ‐ (p=0.011).ConclusionOur results showed that participants with stage 2 AD (SCD.Aβ+) have a higher ptau181 burden at baseline and increasing plasma ptau181 levels over time in a Chinese sample. This suggests that this group is at higher risk for neuropathologic changes, although no differences were found with stage 1 (NC.Aβ+). It should be noted that sample sizes for longitudinal analyses were small, especially for NC, which may partly explain this lack of differences between stages 1 and 2 AD. The SILCODE follow‐up is ongoing, and we plan to test this hypothesis at a later stage.
Chalcone derivate as a promising candidate for treating Alzheimer’s disease
Authors: Haas Murillo Orsatto , Ruaro Thaís C , Gosmann Grace , Zimmer Aline R. 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is a progressive and multifactorial neurodegenerative disease that still has no cure. Different pathological processes contribute to the disease’s development, such as the presence of amyloid beta (Aβ) plaques, neurofibrillary tangles (NFTs), glutamatergic excitotoxicity, oxidative stress, and neuroinflammation1. Chalcones are polyphenolic compounds of natural origin with a wide range of biological activities2, and emerging studies have reported neurotrophic activity, anti‐inflammatory and antioxidant effects, and the inhibition of Aβ aggregation. In this study, we developed a series of innovative molecules based on chalcones and evaluated their cytotoxicity and neuroprotective effects in silico and in vitro experimental platforms.MethodsThe MarvinSketch and SwissADME platforms were used to predict the drug‐like properties of the compounds and their ability to permeate the blood‐brain barrier (BBB). The in vitro assays of the 19 compounds were performed in C6 astroglial and VERO cell lines to assess their cytotoxicity. After that, their neuroprotective effects were evaluated against oxidative and glutamatergic insults in the C6 astroglial cell line. The 3 most promising compounds were tested in a primary culture of astrocytes from the cerebral cortex of a neonatal Wistar rat, and their ability to protect the cell from neuroinflammatory insult (LPS) was evaluated.ResultsThe in silico results indicated that all compounds presented satisfactory drug‐like properties and low or no cytotoxicity. Among tested compounds in in vitro assays, the most promising candidate was CHA 16. It showed a suitable oral bioavailability and a high potential to cross the BBB in silico assays, low cytotoxicity, and a neuroprotective effect against the oxidative and glutamatergic insults in C6 astroglial cells and against the inflammatory insult in primary astrocyte cells. In addition, CHA 16 displayed significant astro‐trophic effects in both cells tested.ConclusionThe compound CHA 16 protected the astrogial cells from oxidative, neuroinflammatory, and glutamatergic toxicity. Together with the high potential for oral use and passage through BBB, it is a promising candidate for clinical testing targeting AD treatment.References:1 Therriault, J. et al. Trends in Molecular Medicine. Volume 28,9:726‐741,2 GOMES, M.N. et al. Chalcone Derivatives: Promising Starting Points for Drug Design. Molecules, 22:1210, 2017
Exploring the correlation between dietary pattern and cognitive functioning in an aging rural Indian population
Authors:   Aishwarya B H , Sahadevan Pravin , Anilkumar Shobha , Rai Pooja , Sundarakumar Jonas S. 
Published: January 2025

AbstractBackgroundStudies on the relationship between diet and cognition have been predominantly from urban and Western populations. However, dietary patterns could vary considerably between populations and the rural Indian population has been grossly underrepresented in this research We aim to investigate the association between dietary pattern and cognitive functioning in an aging, rural Indian population.MethodThe current study utilized a cross sectional design, comprising cognitively healthy participants from the SANSCOG (Srinivaspura Aging Neuro Senescence and COGnition) cohort, an ongoing, aging, community‐based cohort study in a rural, southern part of India, recruited through an area sampling strategy. A total of 3,095 dementia‐free participants, aged 45 years and above, who had completed a dietary assessment questionnaire and underwent a detailed cognitive assessment were included in the study. Cognitive performance was evaluated using a culturally adapted computerized neurocognitive test battery, COGNITO (Computerized assessment of adult information processing), which assesses cognitive domains such as attention, memory, language, visuospatial ability and executive functioning. A composite z score was derived from the average of the individual cognitive domain scores. A linear regression model was employed to investigate the association between dietary pattern and cognitive functioning after adjusting for potential confounders.ResultOur findings showed that participants with lesser fluid intake (3 cups/day [β: ‐0.058, 95%CI: ‐0.106, ‐0.010] and 3‐5 cups/day [β: ‐0.063, 95%CI: ‐0.102, ‐0.025]) had poorer cognitive performance when compared with those with fluid intake of more than 5 cups/day. In addition, consumption of meat and fish was associated with poorer cognitive performance [β: ‐0.079, 95%CI: ‐0.153, ‐0.004] compared to participants who do not consume meat and fish. Further, we did not find any significant association of the other dietary variables that were studied, such as like number of meals per day, consumption of fruits and vegetables, eggs and legumes with cognitive performance.ConclusionOur study highlights the important influence of dietary pattern on cognition. Comprehensive dietary assessments and a longitudinal study design are necessary to make any robust conclusions regarding the precise relationship between dietary pattern and cognitive functioning.
The effects of blood‐brain barrier permeability on Alzheimer’s disease plasma biomarkers and their impact on clinical performance
Authors: Pornteparak Nattanich , Thanapornsangsuth Poosanu , Pongpitakmetha Thanakit , Ongphichetmetha Tatchaporn , Rianaree Juthamas , Luechaipanit Watayuth , Haethaisong Thanaporn , Chongsuksantikul Adipa , Likitjaroen Yuttachai , Hemachudha Thiravat 
Published: January 2025

AbstractBackgroundThe validation of blood‐based biomarkers presents a promising role in Alzheimer's disease (AD) diagnosis owing to their accessibility and diminished invasiveness. However, despite awareness of confounding factors like kidney function, inaccuracies persist in AD diagnosis using plasma p‐tau. Notably, diverse conditions that modify blood‐brain barrier (BBB) permeability have been linked to high plasma p‐tau levels, irrespective of AD pathophysiology.MethodsData were sourced from pooling participants from preceding studies on individuals with encephalopathy and from patients attending a memory clinic, where both plasma and cerebrospinal fluid (CSF) were acquired. Stratifying participants based on binary plasma and CSF p‐tau181 results (using independently validated cut‐offs), the study compared the CSF/plasma albumin quotient (qAlb) between false positive and non‐false positive groups. Univariable linear regression predicting CSF p‐tau181 from plasma p‐tau181 was employed, facilitating the quantification of CSF p‐tau residuals for each participant. The correlations between residuals and qAlb as well as residuals and kidney were examined. A multivariable logistic regression model incorporating qAlb and plasma p‐tau181 to predict AD CSF profile was developed using encephalopathy participants and tested on the memory clinic patients.ResultsA total of 147 participants were included. The qAlb is significantly elevated in the plasma p‐tau false positive group (0.0066 vs. 0.0049, p=0.04658). A notable negative correlation exists between qAlb and CSF p‐tau residuals (Spearman rho = ‐0.0986, p = 0.0347), while no correlation was observed between kidney function and CSF p‐tau residuals (Spearman rho = ‐0.1806, p = 0.2515). Plasma p‐tau181 and qAlb predict AD in the memory clinic with the AUC of 0.78 (95% CI 0.64‐0.92), not different from using p‐tau alone (AUC 0.7778 vs 0.7759, p=0.8626).ConclusionBBB permeability influences the prediction of CSF p‐tau181 from plasma p‐tau181, notably leading to excessive level of plasma p‐tau (ie. false positives). Conversely, in evaluating the effectiveness of integrating qAlb with plasma p‐tau181 for the prediction of AD CSF profiles in clinical contexts, no difference from plasma p‐tau alone was observed. Future investigations should explore whether other biomarkers of BBB influence plasma biomarkers in a similar direction and are useful in identifying potential incorrectly classified patients.
Cavum Septum Pellucidum (CSP) as a Neuroimaging Signature of Head Impact Exposure compared to Non‐exposed Patients with Neurodegenerative Disease and Controls
Authors: Kamps Suzie , Hempel Hugo L. , van Amerongen Suzan , de Bruin Hannah , van der Linden Fleur H.C. , Barkhof Frederik , Scheltens Philip , Ossenkoppele Rik , Vijverberg Everard G.B. 
Published: January 2025

AbstractBackgroundCavum Septum Pellucidum [CSP] is commonly observed on neuroimaging in individuals exposed to repetitive head impacts [RHI] and in post‐mortem examination in Chronic Traumatic Encephalopathy [CTE]. A CSP is proposed as a potential biomarker for CTE, yet prevalence across neurodegenerative diseases and its clinical implications are largely unknown. We assessed CSP prevalence and clinical associations in RHI‐exposed individuals in comparison to veterans with a history of traumatic brain injury [TBI], individuals with a neurodegenerative disease (i.e. Alzheimer’s Disease [AD] or Frontotemporal dementia [FTD]) and Cognitively Unimpaired individuals [CU].MethodThe group‐of‐interest, i.e., individuals exposed to RHI in contact sports or military service (n=66), was compared against age‐ and sex‐matched ADNI‐DOD participants with TBI (n=62) and non‐exposed participants of the Amsterdam Dementia Cohort (AD, n=30; FTD, n=25; CU, n=25). Structural 3D brain MRI scans were visually rated on CSP grade (ranging 0‐4, Figure 1) according to established criteria by two independent raters without access to clinical information. A CSP scored at least grade 2 was considered abnormal. If scores between raters differed, scans were discussed to reach consensus. Inter‐rater reliability was assessed with Cohens’ weighted Kappa (κ). We investigated group differences in CSP grade as well as associations between CSP grade and neuropsychiatric symptoms (using the Neuropsychiatric Inventory [NPI]) and CTE probability (using the Traumatic Encephalopathy Syndrome [TES] criteria).ResultInter‐rater reliability was substantial (κ=0.712). Prevalence of an abnormal CSP differed between groups (χ2=11.72, p=.020). An abnormal CSP was observed most often in the RHI group (43%), followed by TBI (31%, OR=0.589, p=.158), and significantly less in AD (16%, OR=0.255, p=.014), FTD (17%, OR=0.267, p=.029), and SCD (14%, OR=0.222, p=.012) compared to RHI (Figure 2). Across groups, CSP grade was not associated with severity of neuropsychiatric symptoms (F=1.7, p=0.151). An abnormal CSP was observed more in RHI‐exposed individuals with probable (57%) or possible (55%) CTE compared to suggestive of CTE (36%) or no TES (36%).ConclusionA CSP was more prevalent in RHI‐exposed individuals and veterans with TBI compared to patients with a neurodegenerative disease or CU individuals. Presence of a CSP on MRI may be indicative of head impact exposure, especially repetitive impacts.
Effect of Moringa oleifera‐supplemented diets on cognition, neurochemicals, and inflammation makers in the Brain diabetic‐encephalopathic rats treated with Acarbose
Authors: Oyeleye Idowu Sunday , Oboh Ganiyu , Ijomone Omamuyovwi 
Published: January 2025

AbstractBackgroundThe progression of diabetes mellitus (DM) has been associated with changes in brain structure and function, often referred to as “diabetic encephalopathy,” which is characterized by cognitive and neurochemical dysfunction, and identifiable structural changes in brain imaging. This study investigated the effect of Moringa leaf‐supplemented diets (MLSD) on cognition, acetylcholinesterase (AChE), adenosine deaminase (ADA) and arginase activities, reactive oxygen species (ROS), total‐thiol (T‐SH), inflammatory cytokines (TNF‐α, NF‐κB, IL‐6, and IL‐10) levels, caspase‐3 expression, and nuclear factor erythroid 2–related factor‐2 (Nrf2) levels in the brain of DM rats treated with 25 mg/kg bwt acarbose (ACA).MethodThe normal control (NC) rats and diabetic rats were grouped as follows: NC rats, untreated DM rats, DM rats plus ACA, DM rats plus ACA and 2% MLSD, and DM rats plus ACA and 4% MLSD. The NC, DM, and DM plus ACA rats were fed basal diets (i.e., without test samples), while other groups received the corresponding test samples for 28 days. On the last day, cognitive function was assessed using the Morris water Maze and Y‐maze tests. AChE, ADA, ROS, T‐SH levels, TNF‐α, NF‐κB, IL‐6, IL‐10, caspase‐3 expression, and nuclear factor erythroid 2–related factor 2 (Nrf2) levels were measured in the brain.ResultThe untreated DM rats had altered cognition, increased ROS, TNF‐, NF‐B, and IL‐6, caspase‐3 expression and NrF2 levels, and AChE, ADA, and arginase activities, but decreased T‐SH and IL‐10 levels when compared to the NC group. These, however, were reversed in DM rats fed MLSD but were highly significant in DM rats co‐treated with MLSD plus ACA.ConclusionThe findings suggested that a combination of MLSD plus ACA could be explored to combat DM‐induced cognitive dysfunction
“They are perceived to be witches, and some are killed”: Community perceptions of elderly people living with Dementia in Kilifi, A Costal County in Kenya
Authors: Aballa Andrew Okoth , Khakali Linda N , Njoroge Willie , Kamau Lucy Wambui , Shah Jasmit N , Blackmon Karen , Udeh‐Momoh Chi , Nesic‐Taylor Olivera , Merali Zul , Bosire Edna N 
Published: January 2025

AbstractBackgroundPopulation growth and an increase in the number of Africans who survive to old age puts them at a higher risk of developing neurodegenerative diseases such as dementia and Alzheimer’s. Little research has been conducted on community knowledge and perceptions of dementia in rural settings in Kenya.MethodCommunity health volunteers, healthcare workers (HCWs), chiefs and assistant chiefs (n = 35) participated in five focus group discussions, each comprising seven‐ eight people. Key informant interviews (n = 25) were conducted with HCWs, County managers, community leaders and gatekeepers such as chiefs, traditional healers, and faith healers. Audio recordings were transcribed verbatim and thematic analysis used to extract themes.ResultFour main themes identified included: (a) understanding of dementia (b) perceived causes of dementia (c) community perceptions of dementia (d) threats exposed to elderly people suspected of having dementia. Community members did not understand the word “Dementia”. They used a local word “Kusahau sahau” meaning forgetfulness to describe dementia. People with dementia were labelled using stigmatizing words such as “Uendawazimu‐ (madness”, “craziness”), or elderly with “child‐like behavior.” Dementia was perceived as a natural process of aging not requiring intervention. Witchcraftcurses, depression, trauma, substance abuse and HIV/AIDS were other factors attributed to dementia. Limited understanding of dementia led to isolation, neglect, sometimes killing of those suspected to have dementia with the assumptions they were witches.ConclusionThere is poor community understanding of dementia in rural areas of Kenya increasing stigma and discrimination for people with dementia. Retrogressive beliefs and myths predispose people with dementia to neglect, social exclusion, and violent attacks. Social and medical support programs for people with dementia and culturally acceptable tools for quickly diagnosing dementia are lacking. There is need for more research on dementia and Alzheimer’s disease, community awareness creation and policy development aimed to protect elderly populations living with Dementia.
Loneliness as a Predictor of Cognitive Decline in Older Adults: Insights from a Measurement Burst Design Using the Einstein Aging Study
Authors: Kang Jee Eun , Sliwinski Martin J. , Oravecz Zita , Engeland Christopher G. , Katz Mindy J. , Graham‐Engeland Jennifer E. 
Published: January 2025

AbstractBackgroundLoneliness is linked with risk for cognitive decline and dementia among older adults, but the degree to which it predicts future risk is unclear. To investigate if loneliness acts as a predictor of cognitive decline, this study employed a measurement burst design using data from the Einstein Aging Study, where loneliness and cognition were repeatedly assessed daily, for several days, across several years. In this type of data, a major challenge to detecting subtle cognitive changes is the presence of retest/practice effects. We employed a novel process modeling approach (Bayesian Double Exponential Model; BDEM) to distinguish retest learning effects from genuine longitudinal cognitive changes.MethodParticipants (n = 313; English‐speaking, community‐residing adults aged ≥70) underwent up to six waves of annual assessments. Each wave included a 16‐day ambulatory ecological momentary assessment (EMA) burst on mobile phones. Ambulatory assessments consisted of self‐report (including a question about feeling lonely now) and cognitive tests, conducted multiple times daily. This study analyzed the spatial working memory task.Cognitive parameters capturing retest learning rate, peak performance (disentangled from retest learning) and long‐term changes in peak performance were estimated simultaneously using the BDEM. Regression analyses examined associations between mean and standard deviation (SD) of EMA loneliness at baseline and cognitive markers, controlling for demographics and mild cognitive impairment (MCI) status at baseline.ResultA higher mean and a higher variability (SD) of EMA loneliness at baseline predicted higher baseline asymptotic (peak) performance, suggesting worse peak cognitive performance at baseline. However, neither mean level nor variability of EMA loneliness at baseline predicted changes in peak performance after baseline. Notably, a higher variability of EMA loneliness was also associated with slower learning rates from repeated testing across bursts.ConclusionThis study reveals that the level and variability of loneliness in daily life, measured in near‐real time, predict concurrent peak performance and long‐term learning rates in working memory among older adults. Results, particularly regarding loneliness variability, suggest that the experience of loneliness has implications for long‐term learning rates. Not only the mean level of loneliness, but also variations in loneliness, have separate predictive value for cognitive performance over time.