bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision Recommendations to Optimize Neurocognition [PREVENTION] Trial – Intervention Adherence Impacts Cerebral Blood Flow
Authors: Bramen Jennifer E. , Siddarth Prabha , Popa Emily S. , Hodes John F. , Rapozo Molly K. , Glatt Ryan M. , Ganapathi Aarthi S. , Wong Claudia L. , Porter Verna R. , Kim Mihae , Kress Gavin T , Sparks William , Tongson Ynez M. , Panos Stella E. , Hood Lee , Roach Jared C. , Merrill David A. 
Published: January 2025

AbstractBackgroundMedical management and lifestyle are potentially crucial interventions for Alzheimer’s disease (AD). In this study, we present the relationship between adherence of a personalized multi‐modal intervention for AD on change in cerebral blood flow (CBF) after 12‐months.MethodsThe PREVENTION study is an ongoing randomized clinical trial (McEwen, 2001). Thirty‐three participants with biomarker evidence of amyloidosis had completed the study at the time of the analysis (Table 1). While both arms received personalized multi‐modal lifestyle recommendations and four medical visits, the active arm also received dietary counseling, group physical and cognitive exercise, health coaching, and nutritional supplements free of charge. We examined the effects of the 1) the intervention and 2) adherence on CBF. We hypothesized that 1) the active arm and 2) higher intervention adherence would have improved CBF in regions related to level of physical activity (Kleinloog, 2019; Chapman, 2013) and those pertinent to AD. CBF was assessed using arterial spin labeling (ASL). Adherence was measured using the clinician rating scale (CRS), which uses a scale of 1‐7 (Kemp, 1998). Participants were divided into two groups based on a cutoff of 5 (passive acceptance). One participant was excluded from this analysis due to missing CRS data. Effects were assessed using a two‐tailed t‐test.ResultsTreatment arms did not differ in any demographic measures at baseline or CRS. Preliminary findings indicate that regional blood flow declined over one year across the whole sample (Table 2). However, individuals with higher adherence experienced increased blood flow in the fusiform gyrus and less blood flow reduction, compared to those with lower adherence, in the anterior cingulate and hippocampus. Findings were borderline significant in the fusiform and anterior cingulate, but not the hippocampus.ConclusionsIn this small sample, we found evidence that higher adherence increased or attenuated decline in CBF in regions impacted by physical activity, one modality of the PREVENTION intervention. We did not see an effect in the hippocampus, possibly due to small sample size. We did not find an effect of treatment arm, potentially because both receive recommendations and medical management, and did not differ in adherence.
The real‐world implementation strategies for plasma p‐tau217 in tertiary care memory clinics in Thailand
Authors: Thanapornsangsuth Poosanu , Booncharoen Kittithatch , Khieukhajee Jedsada , Luechaipanit Watayuth , Haethaisong Thanaporn , Chongsuksantikul Adipa , Supharatpariyakorn Thirawat , Chunharas Chaipat , Likitjaroen Yuttachai , Hemachudha Thiravat 
Published: January 2025

AbstractBackgroundPlasma tau phosphorylated at Thr217 (p‐tau217) has demonstrated excellent performance in identifying individuals with Alzheimer’s disease (AD) in both research and memory clinic settings. Nonetheless, implementing plasma p‐tau217 into clinical practice remains a challenge requiring careful clinical judgement and conservative interpretation near the cutpoint. The present study proposes a strategy that utilizes Bayes theorem in considering the clinical context, individualized (ie. non‐binary) likelihood ratios and validate it in a multicenter tertiary care memory clinic population in Bangkok, Thailand.MethodPatients from two memory clinics: King Chulalongkorn Memorial Hospital and the Prasat Neurological Institute who underwent CSF analysis for core AD biomarkers or amyloid PET (Florbetaben) were enrolled. Evaluation by neurologists specializing in neurocognitive disorders preceded biomarker testing, resulting in prespecified clinical diagnoses. Pretest odds of amyloid positivity in these subgroups were extrapolated from Jansen, 2022 and Ossenkoppele, 2015. Plasma p‐tau217 (MSD) and p‐tau181 (Simoa) were measured. Participants were randomly divided into training and testing sets. Two Gaussian distributions (Aβ+ and Aβ‐) were generated from plasma p‐tau values in the test set, enabling the calculation of individualized likelihood ratios which posttest odds for each participant were determined. This strategy was compared to multivariable logistic regression using p‐tau, age, and APOE4 as predictor variables. Cross‐validation (ratio= 50:50) was repeated for 5,000 iterations, and performance was assessed using ROC analysis.ResultAmong 132 participants enrolled, 67.4% were female, and 43.2% had dementia. The median age was 68 years (interquartile range: 61, 75). AD was present in 54.5%, as determined by PET (54.5%) or CSF (46%). The strategy incorporating plasma p‐tau217 and pretest odds demonstrated an AUC of 0.979 (95% CI 0.958‐0.998), significantly outperforming logistic regression (AUC 0.948, p=0.0192) and p‐tau217 alone (AUC = 0.939, p=0.003). For plasma p‐tau181, the strategy showed an AUC of 0.926 (95% CI 0.876‐0.968), which is superior to p‐tau181 alone (AUC = 0.864, p=0.006) but not logistic regression (AUC 0.885, p=0.068).ConclusionThe proposed strategy in this study offers a flexible approach to address the limitations of plasma p‐tau in clinical practice, significantly outperforming multivariable logistic regression. An online calculation tool demonstrating its use is available at https://trceid.org/diagALZ/.
Effects of Nigella Sativa oil on Tau Fluorescence in Cys‐variant dGAE and SH‐SY5Y‐derived neuronal cells
Authors: Folarin Royhaan , Imam Moyosoreoluwa 
Published: January 2025

AbstractBackgroundAlzheimer’s disease is a neurodegenerative disease associated with the accumulation of amyloid beta proteins to form plaques and the aggregation of hyperphosphorylated tau to form neurofibrillary tangles. Human fibroblast (SH‐SY5Y) cells endogenously express Tau, and the expression is further amplified upon differentiation into neuronal cells, making it a cell model of Alzheimer’s disease. Nigella sativa oil (NSO) contains 50% thymoquinone and has been used in the treatment of various nervous system disorders. This study therefore aimed at investigating possible inhibitory effects of Nigella sativa oil on the endogenously expressed tau in the neuronal SH‐SY5Y cell model of Alzheimer’s disease and on the aggregation of Tau in the Cys variant dGAE protein.MethodAmyloid fibrilization shall also be induced in vitro in NSO‐treated dGAE by 3 days of thermoshaking at 720 rpm at 37°C. Pre‐ and post‐aggregation samples were then analyzed for amyloid fibril assembly using the Thioflavin S dye and compared for fluorescence using a microplate reader. Neuronal cells were differentiated from human SH‐SY5Y cells using retinoic acid and thereafter incubated with varying concentrations of NSO. Changes in tau phosphorylation was assessed by immunofluorescence using a T‐tau antibody viewed under a Zeiss LSM780 confocal microscope.ResultWhile the untreated post‐aggregation dGAE samples showed higher fibrillar fluorescence than the NSO‐treated post‐aggregation samples, Tau immunofluorescence was also significantly reduced in the NSO‐treated neuronal cells.ConclusionThe Tau‐limiting effect of NSO was observed in dGAE fibrilization and in Tau immunofluorescence in SH‐SY5Y‐derived neuronal cells
Night‐to‐Night Variation of Sleep and Heart Rate in People with Mild Alzheimer’s and Their Caregivers: Preliminary Findings from a Sleep Diary and Contactless Physiological Monitoring at Home
Authors: Ravindran Kiran K.G. , Monica Ciro della , Atzori Giuseppe , Hassanin Hana , Nilforooshan Ramin , Revell Victoria Louise , Dijk Derk‐Jan 
Published: January 2025

AbstractBackgroundChanges in sleep patterns are common in Alzheimer’s disease and impact the quality of life of both people living with Alzheimer’s (PLWA) and their caregivers. Longitudinal recordings and assessment of night‐to‐night variations in sleep and physiology can improve our understanding of how sleep influences clinical outcomes and caregiver wellbeing.MethodWe collected sleep diary and contactless sleep technology data (Withings sleep analyser, WSA) in community dwelling PLWA (N = 16, Age = 72.8 ± 5.7 years, SMMSE = 27.1 ± 1.4), caregivers (N = 8, Age = 74.4 ± 3.8 years, SMMSE = 28.6 ± 0.7) and healthy older adults (N = 23, Age = 70.7 ± 5.5 years, SMMSE = 29.0 ± 0.9) for a period of upto 14 days at home. Group differences were analysed using a mixed model with participants as random effect while coefficients of variation were used to quantify the intra‐individual variability.ResultSleep diary and contactless sleep and heart rate variables were successfully collected for 624 (sleep diary) and 647 (WSA) nights. Analyses of group means of the sleep diary measures revealed that the self‐reported sleep period was significantly longer (p<0.001) in PLWA compared to healthy older adults. The number of reported night awakenings was larger (p = 0.019) in caregivers compared to PLWA. The group mean of nightly minimum heart rate estimated by WSA was significantly lower (p = 0.015) in PLWA compared to healthy older adults (Figure 1).In addition to these differences in group averages, we also observed differences in the night‐to‐night variability of sleep and heart rate measures. The variability of wake after sleep onset and sleep efficiency as reported in the sleep diary were larger in caregivers compared to PLWA and healthy older adults (p<0.05) (Figure 2). The night‐to‐night variability of maximum heart rate was larger in caregivers while the variability of minimum heart rate was larger in PLWA, and caregivers compared to healthy older adults (p<0.05).ConclusionThese data indicated that longitudinal nocturnal recordings of sleep and physiology and analyses of night‐to‐night variability provide insights into the extent of disturbances of sleep and physiology in PLWA and their caregivers.
Assessment of fluid biomarker profiles across disease continuum in a non‐human primate model of sporadic CAA
Authors: Karimi Sohail , Patel Akash G , Nehete Pramod N , Nehete Bharti P , Debure Ludovic , Wang Fengzhu , Botello Raul Rocha , Chahine George , Zhang Qiao , Shao Yongzhao , Mulholland Michele Marie , Gray Stanton B , Hopkins William D , Wisniewski Thomas , Scholtzova Henrieta 
Published: January 2025

AbstractBackgroundVascular Contributions to Cognitive Impairment and Dementia (VCID) is the second most common cause of dementia. Cerebral amyloid angiopathy (CAA), as one of the vascular pathologies underlying VCID, often coexists with Alzheimer’s disease (AD). The New World non‐human primate species, squirrel monkey (SQM), is a preclinical model of AD pathology that naturally develops extensive age‐associated CAA, and therefore holds immense translational value to study biomarkers and novel therapeutic approaches for AD and CAA. We aimed to assess the validity of fluid biomarkers and an Automated Cognitive Testing System (ACTS) to monitor disease progression in SQMs.MethodPlasma and CSF biomarkers of AD pathogenesis and neurodegeneration, cerebrovascular dysfunction/BBB integrity, and inflammation were characterized cross‐sectionally using SIMOA, ELISA, and Luminex immunoassays. A touchscreen‐based ACTS was implemented within young and geriatric SQM cohorts to assess behavioral performance.ResultSimple linear regression models revealed increases in plasma GFAP, sTrem2, YKL‐40 (CHI3L1), and both CSF and plasma NfL concentrations across the SQM lifespan. Plasma concentrations of MMP1 and MMP2 decreased with age, while no simple linear trends in MMP3 or MMP9 were observed. By applying segmented regression analyses, we estimated changepoints in plasma NfL, GFAP, neurogranin, MMP1, MMP2, MMP3, kallikrein‐6 (neurosin), as well as CSF NfL concentrations, ranging from 13.7 to 19.4 years of SQM age. Furthermore, a preliminary analysis among select cohorts of geriatric and young animals demonstrated an age‐associated decrease in the calculated Aβ42/Aβ40 ratio and albumin index, among time‐matched CSF and plasma samples. Training on an ACTS match‐to‐sample (MTS) task revealed differences in cognitive performance, as young SQMs required significantly fewer trials than geriatric animals to achieve a passing criterion. Cognitive assessments continue on a series of more advanced behavioral tasks. Integration of all measures with neuroimaging correlates are underway.ConclusionThe present characterizations of biomarker trajectories may help identify pathology onset and disease progression in the SQM model. Further portrayal of this species will advance our understanding of CAA pathogenesis, promoting further discoveries of diagnostic biomarkers and novel drug targets.
The association between grey matter microstructural MRI biomarkers, mid‐life blood pressure, and late‐life Alzheimer’s disease pathology
Authors: Weston Philip SJ , Coath William , Brown Thomas M. , Scott Catherine J , Malone Ian B. , Arstad Erik , Awais Ramla , Sander Kerstin , Thomas David L , Dickson John C , Schöll Michael , Richards Marcus , Fox Nick C , Zhang Hui , Cash David M , Schott Jonathan M 
Published: January 2025

AbstractBackgroundWith an aging population, it is essential to identify subtle features of brain pathology – both neurodegenerative and vascular – at an early stage, which may predict risk of future decline. We used diffusion MRI (dMRI) to assess grey matter cortical microstructure and investigate associations with 1) Alzheimer’s disease (AD) pathology and 2) mid/late‐life vascular risk (as measured by blood pressure (BP)).Method151 asymptomatic individuals from the British 1946 birth cohort underwent combined PET/MR with [18F]florbetapir Aβ‐PET at ∼73yrs, and [18F]MK‐6240 tau‐PET at ∼76yrs. Multi‐shell diffusion MRI was acquired; neurite orientation dispersion and density imaging (NODDI) quantified orientation dispersion index (ODI), a proxy measure of dendritic morphology/complexity, with DTI measuring mean diffusivity (MD), a less specific measure of degenerative change. Cortical volume was estimated using GIF. PET SUVRs were calculated. Amyloid load was assessed in a cortical composite region, with tau PET and MRI measures assessed in 1) a temporal meta‐ROI (analogous to early Braak stages), and 2) a larger neocortical meta‐ROI, analogous to later Braak stages. BP measurements were taken throughout mid and late life, at ages 43, 53, 63, and 73.ResultSeventy participants were amyloid positive (A+), of whom 27 were tau positive (T+). Global cortical ODI was significantly lower in A+/T+ than A+T‐ (p=0.005) and in A+/T+ than A‐/T‐ (p=0.001), but with no significant difference between A+/T‐ and A‐/T‐. The same pattern was found for ODI in the temporal ROI. No consistent differences were found across A/T groupings for MD or volume. MD (both global and temporal) at aged 76 showed significant associations (p<0.05) with BP at ages 43, 53 and 63, but not at 73. These association remained after adjusting for A/T pathology and cortical volume. For ODI, associations with mid‐life BP were less consistent.ConclusionMid‐life BP is associated with late life cortical microstructural breakdown, as measured by MD, in the absence of detectable volume changes and independent of Alzheimer’s disease (AD) pathology. ODI appears to be more sensitive and specific to dendritic tau‐related changes. Cortical dMRI offers promise in the presymptomatic identification, staging and risk stratification of both AD and vascular dementia.
The impact of mid‐life cardiovascular health on cognitive change in a bi‐ethnic cohort
Authors: Vazquez Janette , Bernal Rebecca , Trevino Hector A , Velarde Angel G , Goss Monica , van Lent Debora Melo , Hazuda Helen , Wang Chen‐Pin , Satizabal Claudia L 
Published: January 2025

AbstractBackgroundVascular risk factors are known contributors to cognitive decline and dementia; however, their impact on cognitive change in diverse samples is understudied. In this study, we investigated the effect of the AHA Life’s Simple 7 (LS7) on cognitive decline in the bi‐ethnic San Antonio Longitudinal Study of Aging (SALSA) cohort.MethodWe included 403 participants (mean age 57.9±3.8, 58.5% female, 52% Mexican Americans (MA), Table 1) from SALSA who were part of the San Antonio Heart Study (SAHS) launched in 1979. LS7 scores (score range 1‐13) integrated mid‐life data on diet, physical activity, body mass index (BMI), smoking, total cholesterol, blood pressure, and fasting blood glucose. We combined intermediate and ideal LS7 categories, using poor LS7 as the reference. The Mini Mental State Examination (MMSE) assessed global cognition at SALSA baseline (1992‐1996) and three follow‐up examinations. The study included individuals with complete data for computing LS7 scores, a baseline MMSE score, and at least one follow‐up MMSE exam. We used generalized estimating equations to explore the relationship between total LS7 score and single LS7 components with cognitive decline, both in the total sample and by ethnicity. The statistical model was adjusted for age, sex, education, income, and ethnicity (total sample only).ResultNo relationships were observed between LS7 total score and cognitive decline. In the overall sample and among MA, meeting intermediate or ideal physical activity goals demonstrated a mitigating effect on cognitive decline (β±SE, 0.065±0.032, p = 0.041; 0.147±0.048, p = 0.002, respectively, see Table 2 and Figure 1). Additionally, maintaining blood glucose below 125 mg/dL was associated with slower cognitive decline (0.182±0.074, p = 0.014, Table 2) among non‐Hispanic White (NHW) but not among MA (0.035±0.098, p = 0.725, Table 2). In contrast, BMI under 30 was associated with accelerated cognitive decline (‐0.012±0.050, p = 0.025, Table 2) among MA but not among NHW (‐0.012±0.056, p = 0.836, Table 2).ConclusionWhile the LS7 total score showed no significant association with cognitive decline in our bi‐ethnic cohort, notable associations were found for physical activity and blood glucose, highlighting their potential as effective preventative measures. Nonetheless, future multi‐ethnic studies are encouraged to replicate our findings, especially in larger sample sizes.
Impact of type 2 diabetes mellitus on Alzheimer’s disease ‐related pathology preceding cognitive impairment
Authors: Yu Yang Yang , Nowell Joseph , Edison Paul 
Published: January 2025

AbstractBackgroundAlzheimer’s disease and type 2 diabetes mellitus rank among the top ten leading global causes of death. The association between diabetes and Alzheimer’s is linked to chronic low‐grade inflammation, hyperinsulinemia, and the interplay between peripheral and central insulin resistance, influencing insulin signalling. We evaluated the association between diabetes and Alzheimer’s‐related neuropathology in cognitively unimpaired older adults with diabetes.MethodsWe compared tau, cerebral glucose metabolism and amyloid in 147 cognitively normal participants, comprising 32 clinically diagnosed with diabetes and 115 without diabetes, from the Alzheimer’s Disease Neuroimaging Initiative dataset. We processed 329 available PET scans for 18F‐AV‐45, 18F‐flortaucipir and 18F‐fludeoxyglucose (FDG). Independent t‐tests and multivariate analysis were conducted for regions of interest (ROI) values, encompassing the global cortex and subsequent brain cortices, the medial temporal lobes, striatum, thalamus, and the anterior and posterior cingulate. Voxel‐wise analysis using SPM was also performed for these groups. Amyloid positive and negative subjects were evaluated separately.ResultsCognitively unimpaired diabetic subjects exhibited higher tau uptake compared to the non‐diabetic group in the whole brain (global brain value) and individual brain cortices, including the frontal, temporal, parietal, and occipital lobes. In diabetic subjects with negative amyloid status, significance was observed in the whole brain, as well as the parietal, temporal, medial temporal lobes, and the striatum. Reduced FDG uptake was only evident in diabetic subjects with positive amyloid status in the striatum. Increased amyloid deposition was noted in the medial temporal lobe and hippocampus in subjects with diabetes compared to those without.ConclusionsNeuropathological changes in the diabetic brain precede the manifestation of cognitive decline. Specifically, there is an increase in the presence of tau in the diabetic brain even in the absence of amyloid, indicating that tau may be the predominant driver of cognitive decline in diabetes.
Using community health workers to assess the prevalence of dementia in a community based sample of older Zambians
Authors: Mataa Mataa M , Kalungwana Lisa , Bwalya Chiti , Simushi Faith , Hachaambwa Lottie , Mwango Linah , Namangala Coolwe , Yankae Leroy , Daniel David , Tanner Jeremy A. , Elafros Melissa A 
Published: January 2025

AbstractBackgroundIn Zambia, dementia prevalence is unknown due to limited community awareness and a lack of providers skilled in recognizing and diagnosing this disease. Community healthcare workers (CHWs) are widely utilized across sub‐Saharan Africa to improve health care access, particularly HIV services. CHWs may be an untapped resource to raise awareness, screen for dementia, and support dementia care in the community. This study is piloting a community‐based model using CHWs to screen for dementia and associated risk factors in a population‐based sample of older Zambians.MethodsTen Zambian CHWs underwent a five‐day training led by a neuropsychologist and neurologist on symptoms of dementia, myths, and administration of the 10/66 dementia screening protocol. CHWs were then deployed in two high‐density Lusaka communities to enroll adults age >55 and a caregiver from randomly selected households. Demographics, medical history, diet, anthropomorphic measurements, HIV, and glucose testing were collected. Dementia was defined using the CSI‐D with a neuropsychologist regularly assessing community administration to assure standardizationResultsTo date, 185 Zambians (mean age 67; 66% female, mean education 5.7yrs) have been enrolled. Mean household income was ZMW 1339 ($52/month). Fifty percent endorsed food insecurity in the past 30 days, whereas 25% drank alcohol. Twenty‐four (13%) participants were HIV‐positive. One hundred and two (55%) participants regularly attended community social activities. Caregivers reported that 13 (7%) participants regularly forgot family member’s names, 7 (4%) got lost in the community, and 5 (3%) got lost at home. On dementia screening, 63 (34%) screened negative for dementia (dfscore <0.12), 23 (12%) screened in the intermediate range (dfscore 0.12 to <0.184) and 99 (54%) participants screened positive for possible dementia (dfscore ≥0.184).ConclusionsCHWs can be trained to reliably administer dementia screening measures and may serve as a resource for dementia care. High rates of positive dementia screening raise concern that these measures may be overly sensitive in this population. We are conducting additional neurological evaluation and neurocognitive testing with participants to assess CSI‐D sensitivity and specificity and to determine the prevalence of dementia and dementia risk factors in Zambia.