bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial Extent as a more sensitive amyloid biomarker for early stages of Alzheimer’s disease
Authors: Farrell Michelle E. , Thibault Emma G. , Becker Alex , Price Julie C , Schultz Aaron P. , Properzi Michael J , Buckley Rachel F. , Jacobs Heidi I.L. , Hanseeuw Bernard J , Sperling Reisa A. , Johnson Keith A. 
Published: December 2023

AbstractBackgroundDespite considerable advances in beta amyloid (Aβ)‐PET imaging over the last decade, the standard approach of estimating the average neocortical Aβ burden remains largely unchanged. However, as research and clinical trials increasingly shift earlier in the disease process, measures of how far Aβ has spread throughout the cortex (spatial extent) may prove more sensitive than average neocortical magnitude for detecting and quantifying early Aβ deposits and their association with future tau proliferation and cognitive decline.MethodClinically‐normal individuals (n = 214) were included from the Harvard Aging Brain Study with longitudinal PIB‐PET (2‐4 scans, median = 4.7±2.7 years) and annual cognitive data (median = 5.2±2 years), as well as a subset (n = 181) with flortaucipir (FTP)‐PET. Spatial extent (EXT) was computed as the number of cortical ROIs (n = 62, Desikan atlas) above their ROI‐specific threshold for Aβ positivity. EXT was compared to a traditional mean neocortical DVR using logistic growth modeling. Receiver Operator Characteristic (ROC) curve analyses evaluated EXT’s ability to identify baseline PIB‐ individuals (<1.19DVR/24CL) who progressed to PIB+ at 3‐year follow‐up. Linear Mixed Effects (LME) modeling assessed baseline EXT (or DVR) as a predictor of increasing inferior temporal tau (IT FTP SUVR) and cognitive decline on the Preclinical Alzheimer’s Cognitive Composite (PACC).ResultEXT begins rising below the neocortical DVR threshold (Figure1A), reaching a maximal growth rate of 14 ROIs per 0.1 DVR increase (∼10CL) and plateauing as full cortical EXT is achieved starting at ∼1.5DVR/68CL. A 3‐ROI EXT threshold predicts progression from PIB‐ to PIB+ in 3 years (AUC = .97, SE = .82,SP = .97), outperforming neocortical DVR (AUC = .92, SE = .65,SP = .94, Figure1B). EXT provides a stronger biomarker of Aβ change than DVR (lower coefficient of variation, Figure2) across the Aβ continuum due to its low variance, even after EXT has plateaued. Baseline EXT is also a stronger predictor of increases in IT FTP SUVR (Figure 3A, η2
EXT = .25, η2
DVR = .20) and PACC decline (Figure3B, η2
EXT = .28, η2
DVR = .22).ConclusionBy describing the spread of Aβ throughout the cortex rather than average neocortical Aβ burden, spatial extent provides a more sensitive measure of Aβ at early, preclinical stages of AD that may improve design of AD prevention trials and open new avenues for research into AD pathogenesis.
Glymphatic function maintains sleep‐sensitive cognitive performance and predicts overnight changes in plasma amyloid β in humans
Authors: Balkrishnan Shilpa , Giovangrandi Laurent , Vanderweerd Carla , Singh Tarandeep , Jaffe Michael , Lowenkron Jeffrey , Lim Miranda , Iliff Jeffrey J , Dagum Paul 
Published: December 2023

AbstractBackgroundDuring sleep, the glymphatic system facilitates rapid exchange of fluid through brain tissues, clearing solutes, including amyloid β (Aβ), tau, and α synuclein that accumulate through the course of waking activity. Glymphatic clearance is widely believed to underlie the restorative effects of sleep on cognition, and its impairment is proposed to reflect the biological basis for the corrosive effects of sleep disruption. We sought to determine if glymphatic function or sleep EEG predicted changes in cognitive performance and overnight differences in Aβ biomarker levels using a new non‐invasive investigational medical device (IMD) to measure glymphatic function by dynamic impedance spectro‐tomography.MethodEighteen healthy 50‐65 y/o participants were enrolled in a cross‐over randomized control clinical trial encompassing one night of sleep and one night of sleep deprivation. Participants were instrumented with the IMD and overnight change in brain parenchymal resistance to flow, R, was measured. Sleep EEG powerbands, slow (0.4‐1Hz), delta (1‐4Hz), beta (15‐30Hz), and time spent in N2, N3 and REM sleep were derived from the device EEG. In both sleep and sleep deprivation interventions, cognitive tests (symbol digit modality test, SDMT; psychomotor vigilance test, PVT) were administered at 7am and blood Aβ biomarkers (Aβ40; Aβ42) were taken at 10pm and 7am.ResultOvernight parenchymal resistance R predicted intraindividual paired differences (sleep – sleep deprivation) in cognitive test scores (A SDMT ρ = ‐0.65, p = 0.003; B PVT STD RT, ρ = 0.41, p = 0.095) and Aβ42 blood amyloid biomarker changes (C Aβ42 ρ = ‐0.53, p = 0.03; D Aβ40 ρ = ‐0.33, p = 0.21). Sleep EEG powerbands and time spent in N2, N3, and REM sleep were not predictive of sleep‐related changes in cognition or plasma Aβ biomarker levels.ConclusionGlymphatic function, measured continuously by dynamic impedance spectro‐tomography, predicted changes in the restorative effect of sleep on cognition and plasma Ab biomarker levels as hypothesized, but not previously demonstrated. In contrast, sleep EEG powerbands and time spent in N2, N3 and REM were not predictive. Detection of glymphatic impairment in real‐world settings may permit (i) early identification of individuals at‐risk for developing sleep‐related Alzheimer’s disease pathology, and (ii) enable precision targeted enhancement of glymphatic function to enhance glymphatic function and pathological protein clearance.
Functional Connectivity and White Matter integrity of intercommunity hub nodes in Subjective Cognitive Decline
Authors: Nowling Duncan , Bustos Nicholas , Barlis Katie L , Crull Jory , Lawson Andrew , Benitez Andreana , Jensen Jens H. , Dean Brian , Mintzer Jacobo , Joseph Jane E 
Published: December 2023

AbstractBackgroundSubjective Cognitive Decline (SCD) is considered an early preclinical stage of Alzheimer’s Disease and related dementias (ADRD) which may show promise for targeted preventative treatments. Subtle changes in functional connectivity and white matter integrity (WMI) may occur in SCD. Few studies have applied both functional graph theory (GT) and diffusional kurtosis imaging (DKI) techniques in tandem to identify differences in vulnerable network hubs. We addressed these issues by applying GT and DKI to study differences in intercommunity brain hubs. The hypothesis was that in hubs identified in healthy controls, SCD subjects’ hubs would show decreased GT diversity coefficient (DC) and DKI mean kurtosis (MK).MethodImages were acquired on a Siemens PRISMA scanner. Matlab was used to calculate DC and identify 5 hubs in 107 healthy controls (HC) and DC in 30 SCD (93 females, mean age = 67.51). SCD classification was determined by a comprehensive clinician evaluation or Everyday Cognition average item score>1.6, with objectively healthy cognitive performance (Montreal Cognitive Assessment score>22). Hub DC was the target in GLMM analysis, with diagnosis as predictor. Mean Kurtosis (MK) was analyzed in DSI Studio’s cross‐sectional connectometry using the hubs as seeds. Only the covariate of gray matter volume approached significance (p = .059), and was included in analysis. Mean age, education, head motion, and sex balance did not significantly differ between groups.ResultAll hubs had lower DC in SCD compared to HC (p ≤ .006). Connectometry identified positive correlation between MK and diagnosis in Left hemisphere tracts associated with two hubs: Inferior Fronto‐Occipital, Extreme capsule, and Uncinate tracts from Insular cortex, and Superior Longitudinal, Superior Corticalstriatal, Arcuate, Frontal Aslant, and Corticalspinal tracts from Middle Frontal gyrus.Conclusion
Conclusion
Rs‐fMRI findings show that intercommunity functional hubs are weaker in SCD compared to healthy individuals. Furthermore, the study identified a relationship of higher MK values in SCD for hubs located in insular cortex and middle frontal gyrus, all left hemisphere biased. Higher MK in SCD also runs counter to our hypothesis but is supported by recent paradoxical increase theories of decline. WMI differences between groups may be subtler than functional changes, warranting examination of the 2 modalities’ relationship.
Peer group leadership for dementia health risk reduction
Authors: Hynes Mary T , Kastner Monika , Anderson Nicole D. , Astell Arlene J. 
Published: December 2023

AbstractBackgroundWith the worldwide number of persons with dementia predicted to triple by 2050 and a current lack of curative treatment [1], reduction of modifiable risks is increasingly important. In 2020 the Lancet Commission on Dementia, Prevention, and Care reported on twelve health risk management factors that could potentially reduce the risk of dementia [2]. Peer support groups have a history in supporting self‐management of health risk behaviour [3,4]. We wanted to learn if older adults have successfully provided peer leadership in group interventions for older adult health management.MethodUsing the Joanna Briggs Institute methodology for scoping reviews we searched three databases (Medline, Embase, and AgeLine) for articles describing older adult leadership for older adult health improvement in older adult health promotion or improvement groups. From the initial 16,000+ results, 19 studies met the criteria for full text screening and analysis.ResultOf the 19 studies, 12 used peer leaders and seven had a reciprocal support model. For those using peer leaders, training varied from none to 30 weeks. Older adult leadership or reciprocal support occurred in a range of settings. There were studies examining an older adult run seniors centre and a supportive community engagement program. Six studies focused on diabetes or hypertension, conditions linked with dementia risks. Interventions lasted from four weeks to 24 years. No quantifiable patterns of health management were observed. The only pattern that emerges is that positive physical and behaviour changes occurred more often when peer leaders or co‐facilitators were expected to motivate or encourage participant engagement or mutual support and where expectations included participant goal setting behaviour. Most of the studies of 12 weeks or less did not see lasting changes.ConclusionsWhen asked participants preferred and appreciated peer leadership; however, peer leadership itself was not sufficient for positive health changes. Research with a sharing and empowerment focus within groups often led to improved self‐efficacy and self‐management behaviours. Research with longer participant engagement may result in longer lasting health habits.
Economic burden of transitions to later stages of Alzheimer’s disease in Europe: elevating the sense of urgency to treat
Authors: Razavi Moaven , Herring William L , Gillis Cai , Pemberton‐Ross Peter , Maserejian Nancy Nairi , Nejati Mina 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) significantly impacts individuals, families, and society worldwide. In Europe, it affects approximately 10 million people, leading to considerable healthcare costs, caregiver burden, and reduced productivity.1 It is crucial to slow down AD progression in order to alleviate the rising burden of the disease.MethodTwo targeted reviews were conducted, one on the prevalence of individuals with biomarker‐confirmed AD pathology and the other on the costs associated with AD by disease stage and care setting. The most recent prevalence1,2,3,4,5,6,7,8 and cost9,10,11,12,13,14,15,16,17,18 data were identified for selected countries, including the UK, France, Germany, Italy, Spain, Sweden, Netherlands, Finland, Switzerland, Estonia, and the Czech Republic. Regression‐based or linear extrapolation methods were applied to fill the existing data gaps where appropriate. All costs were converted to USD and adjusted for inflation to reflect 2022 values.ResultThe national costs associated with annual transitions across all AD stages were estimated to be ($11.4bn) in Germany, followed by France ($6.2bn), UK ($5.2bn), Spain ($3.7bn), Italy ($3.2bn), Switzerland ($1.9bn), Sweden ($1.4bn), Netherlands ($1.07bn), Finland ($0.8bn), Czech Republic ($0.7bn), and Estonia ($0.03bn). Early‐stage progression, with the largest number of individuals transitioning from mild cognitive impairment (MCI) to mild AD, accounted for more than half of the total transitioning costs in the UK, Spain, Finland, Netherlands, Czech Republic, and Estonia. However, the highest cost burden varied across the countries. In Germany, Italy, and Switzerland, similar to previous estimates for the US,19 the highest burden was associated with late‐stage progression from moderate to severe dementia, despite the relatively lower number of such transitions. This is likely due to the more expensive institutional care in these countries. Our findings further suggest that including the economic value of uncompensated caregiving substantially increases the total costs while leading to greater variability in estimates. The interpretation of these results should take into account data limitations and the assumptions made in the analysis.ConclusionThe economic burden of AD increases as disease progresses. Total costs and the underlying components vary across health systems and regions. Nevertheless, universally, any treatment that slows down the disease progression could result in substantial costs savings.
Treating microRNA dysregulation in AD mice models: A systematic review
Authors: Salcido‐Montenegro Alejandro , Quintanilla‐Sanchez Carolina , Leroy Karelle 
Published: December 2023

AbstractBackgroundEfficient treatments for Alzheimer’s disease are still not available. As miRNAs are becoming therapeutic targets, a critical review of the evidence in AD mice models is required.MethodThis is an ongoing review, following the recommendations of PRISMA guidelines. The search was conducted in in MEDLINE, Scopus and ProQuest. Only peer reviewed interventional studies of in vivo AD mice models are eligible. Information about model, intervention, targeting miR and efficacy measures is being extracted.ResultFrom the 5239 retrieved studies, 10 have been completely reviewed. The most common targeting miRNA is miR‐146a, followed by miR‐124, miR‐30b and miR‐138. Cognitive impairment was rescued by intracerebral injections of miR‐146a antagomir (Islam et al., 2021; G. Wang et al., 2016), inhalation of a chemically modified 146a mimic (Mai et al., 2019), by environmental enrichment (Nakano, Kubota, Hashizume, et al., 2020) and by the intracerebral injection of bone‐marrow derived mesenchymal cells (Nakano, Kubota, Kobayashi, et al., 2020). Molecular mechanisms involved are decrease in neuroinflammation and tau phosphorylation and an increase in the synaptic density. Antagomirs of miR‐124 in the Tg2576 and P301S models, improve memory deficits, while improving synaptic density and function and decreasing tau‐phosphorylation and aggregation, respectively (Hafez et al., 2021; X. Wang et al., 2018). However, mice injected with oA42i, reported a downregulation of miR‐124 and intervention with 3,4‐dihydroxyphenylethanol produced a behavioral improvement as well (ArunSundar, Shanmugarajan, & Ravichandiran, 2018). miR‐138 and miR‐30b antagomirs decreased memory deficits by means of synaptic morphology and function improvement in the 5XFAD and APPswe/PSEN1dE mice (Lu, Tan, & Wang, 2019; Song, Hu, Zhang, Teng, & Chen, 2019). Nevertheless, the longest incubation time was 1 month and in any of the studies the intervention was repeated. No side effects were reported.ConclusionSeveral interventions targeting miRNAs are emerging and although positive effects are seen in the short run, longer observation times are needed. The molecular mechanisms under the effect of miRNAs are complex, as shown by the beneficial effects of both agonists and antagonists of miRNA‐146a. More studies are needed to elucidate the main mechanisms and the most adequate therapeutic approach.
In what ways can digitally mediated epistemic practice enable organisational learning in dementia care practice?
Authors: Bartle Caroline B 
Published: December 2023

AbstractDementia Care is highly skilled work. Delivering person centred care requires an understanding of multiple bodies of knowledge combined with situated knowledge of the person in their environment. However traditional training methods often fall short, with limited learning transfer to practice. Training is often developed to meet mandatory requirements, but often lacks local contextual knowledge essential for learning transfer. ‘Standard’ programmes often provide limited opportunity to develop skills to meet the diverse range of needs typically found within a dementia care service. Ineffective learning systems are common and can lead to systemic problems where skills deficits and poor practice become embedding, escalating costs for care organisations.New approaches that utilise data to level technologically driven solutions for more effective workforce planning are required. Education technologies that enable learning in the flow or work alongside data derived from digital care planning systems can be used in intelligent ways to design and enable rapid, responsive learning in practice. Workforce development data delivered in real time enables practitioners to adapt their approach. For example, that enable reflective practice can counteract the impacts of emotional labour and tackle unconscious bias. However, how can this work effectively and what are the risks? What opportunities does technology provide to support staff wellbeing? What are the opportunities and limits of utilising data? For example, data driven feedback loops may minimise, or indeed eradicate opportunities for deep learning.The presentation will summarise the initial literature review exploring how epistemic practices evolve in dementia care services to enable organisational learning considering:
In what ways do different data practices impact organisational learning?

How do blended approaches impact epistemic practices?

What opportunities might there be for digitally mediated practices to improve dementia care?
Precision Recommendations to Optimize Neurocognition [PREVENTION] Trial: Preliminary Results
Authors: Merrill David A. , Bramen Jennifer E. , Hodes John F. , Rapozo Molly K. , Glatt Ryan M. , Ganapathi Aarthi S. , Wong Claudia L. , Porter Verna R. , Kim Mihae , Tongson Ynez M. , Bookheimer Tess Helen , Popa Emily S. , Meysami Somayeh , Nomura Natsuko , Choden Pema , Dye Richelin V. , Togashi Tori , Loong Spencer , Panos Stella E. , Miller Karen J. , Siddarth Prabha , Roach Jared C. 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a complex neurodegenerative condition that requires a comprehensive treatment approach. In addition to pharmacologic treatment, managing existing medical conditions and incorporating lifestyle modifications, such as diet, cognitive training, and exercise, are potentially crucial components of an effective intervention. In this study, we present preliminary results of a personalized multi‐modal intervention for AD.MethodsThe Precision Recommendations to Optimize Neurocognition (PREVENTION) study is an ongoing 12‐month randomized clinical trial. Fifty participants (mean age 71.9(SD = 7.2); 24 Female) with biomarker evidence of AD amyloidosis have been recruited. While both arms receive personalized data‐driven, lifestyle recommendations designed to target multiple systemic pathways implicated in AD, the active arm also receives health coaching, dietary counseling, exercise training, cognitive stimulation, and nutritional supplements. Comprehensive clinical, cognitive, neuroimaging, and genetic data are collected at baseline, and post‐intervention. Herein, we examined the effects of the intervention on global cognition (MoCA) and regional brain volumes using general linear mixed models and compare to literature values (or historical controls).ResultsParticipants in the two groups (23 active; 27 control) did not differ significantly in demographic, cognitive, or brain imaging measures at baseline. Thirty‐one participants (16 active; 15 control) have completed the study. Within‐group 12‐month changes in MoCA (active:‐1.4(3.5); control:‐1.7(3.6)) were not significant, did not differ significantly between groups and were borderline (p = .08) less than expected rate of decline. While both groups declined significantly in hippocampal volumes, percent changes in total gray matter, entorhinal cortex, and precuneus volumes were significantly less in the active arm (Table).ConclusionIn this preliminary analysis of an active multimodal lifestyle intervention paired with personalized health optimization, regional volume loss in certain key areas of interest in AD was significantly lower in the active arm compared to control; further, the decline in global cognition was not statistically significant and was attenuated for the entire cohort compared to literature values. These preliminary results in a relatively small cohort suggest the intervention may beneficially impact cognition, memory, and brain structure. Future analyses will focus on elucidating changes in the biological systems being targeted by the intervention to help uncover the underlying mechanisms.
Peripheral and Central Nervous System Immune Effects of Bacillus Calmette‐Guérin (BCG) Vaccination in older adults with and without cognitive impairment
Authors: Kodali Mahesh Chandra , Young Katie , Kivisäkk Pia , McManus Alison J. , Gerber Jessica A. , Faustman Denise L. , Weinberg Marc S. , Arnold Steven E. ,   Massachusetts General Hospital Alzheimer’s Clinical and Translational Unit
Published: December 2023

AbstractBackgroundThe live‐attenuated vaccine Bacillus Calmette‐Guérin (BCG), is widely used for the prevention of tuberculosis, and has myriad non‐specific beneficial effects in T1DM, multiple sclerosis, decreasing all‐cause childhood mortality, etc. Alzheimer’s Disease (AD) is a complex neurological disease. The innate immune system, intimately involved in the early and late phases of AD, may prove an ideal target for mono‐ or multi‐pronged therapy against AD. Data from multiple population health studies find that BCG treatment for bladder cancer is linked with decreased incidence of AD. Preclinical data also supports an AD‐beneficial effect of the vaccine. While mechanisms of some of these non‐specific vaccine effects have been elucidated, the mechanism behind BCG’s putative central nervous system (CNS) benefits is unclear. Here, we conducted a pilot open‐label study of the BCG (Tokyo strain) in the older adults to study CNS beneficial effects, particularly as they pertain to AD.MethodsBaseline measures of participants (N = 16) with or without mild cognitive impairment (MCI) included cognitive and neuropsychological testing, phlebotomy, and lumbar puncture (LP), followed by an initial intradermal BCG, with a booster given 1mo later. Neuropsychological testing, phlebotomy and LP were repeated at 3mo, 6mo (no LP), and 12mo. The primary endpoints include 1) the safety of the vaccine in older adults and 2) target engagement. Secondary and exploratory endpoints include 1) functional, immunological, and AD‐related biomarker measures and 2) cognitive and neuropsychological effects.ResultsOur interim analysis demonstrated an overall improvement in repeatable battery for neuropsychological status (RBANS) total score index (TSI), notably in subsections of delayed recall, and visuospatial and constructional indices. Our results also show robust peripheral target engagement and the induction of trained immunity in the peripheral blood cells. We will further show the effects on various AD‐related biomarkers in plasma and cerebrospinal fluid.ConclusionThese findings support that the BCG vaccine is safe in older adults and may improve cognition (enrollment of a placebo control group is underway). A further study including subjects with MCI and AD is ongoing. Our interventional studies with BCG begin to explore whether this strategy of retraining the neuroimmune axis can prevent and/or treat AD.