bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Plan to Impact ‐ progress towards targets of the WHO Global action plan on dementia
Authors: Arthurton Lewis , Lynch Chris , Weidner Wendy S 
Published: December 2022

AbstractBackgroundThe WHO Global action plan on the public health response to dementia 2017‐2025 was universally adopted by Member States in 2017. Every year since, Alzheimer’s Disease International (ADI) has produced the report ‘From Plan to Impact’ reviewing progress and barriers towards the goals of the plan, including the development of national dementia plans worldwide and shining a light on the challenges, responses and innovation around the COVID‐19 pandemic.MethodADI will conduct desk‐based research, distributing a survey to its 120 member associations. For non‐ADI Member states, further desk‐based research will be conducted by contacting associations, officials and ministries in those countries. The survey will predominantly seek to determine the status of a national dementia plan, or dementia integrated into another health plan (global action area 1), with further questions seeking to illuminate the remaining six action areas, including diagnosis, treatment, care, support, research, risk reduction and support for carers, and continuing to discover the impact, disruption and response to COVID‐19.ResultHabitual monitoring of the global national dementia plan environment has shown that new plans have been approved in Iran and Czech Republic. Armenia and Brazil appear to be making advances towards the implementation of their own national dementia plans. Preliminary findings suggest that Member States are likely to miss the target of 75% of countries (146) having a national dementia plan by 2025, findings mirrored by the WHO Global status report on the public health response to dementia, unless a concerted effort is made to rectify this. COVID‐19 has exposed inadequacies in the preparedness of governments to care for and support those living with dementia and their carers. We expect further granularity of data to become available throughout the development of the report.ConclusionOnly with robust national dementia plans can governments prepare their health and care systems to meet the needs of their population. This research and report will focus attention on those governments and areas where an acceleration to progress is required, identifying gaps and shining a light on best practice in other countries and regions that can act as a stimulus and motivation for others.
The Clinical Features of Patients with Alzheimer’s Disease and a History of Traumatic Brain Injury
Authors: van Amerongen Suzan , Caton Dewi , Pijnenburg Yolande A.L. , Scheltens Philip , Vijverberg Everard G.B. 
Published: December 2022

AbstractBackgroundTraumatic brain injury (TBI) has been associated with a greater risk of developing Alzheimer’s disease (AD). Previous studies have argued that AD patients with TBI history have a differences in age of disease onset, cognitive features and neuropsychiatric symptoms (NPS), but current evidence is still limited and did not always take into account injury characteristics, such as age at injury, TBI frequency, and severity. The primary objective of this study is to examine whether a history of TBI and specific injury characteristics are associated with differences in age of disease onset, cognitive features and NPS in biomarker proven AD patients.MethodBiomarker proven AD patients (CSF or amyloid PET, stage MCI or dementia) were selected from the Amsterdam Dementia Cohort. TBI events were classified by severity, frequency and age at injury (TBI <25 or ≥25 years). Cognitive composite scores were calculated from results of a neuropsychological test battery. Neuropsychiatric symptoms (NPS) were assessed with the Neuropsychiatric Inventory Questionnaire (NPI‐Q). Linear regression analyses were utilized to examine the association between TBI, injury characteristics and clinical outcome measures.ResultAmong the 1755 selected AD patients (mean age 65.2), 166 patients (9.5%) reported ≥1 TBI in their history. Overall, a history of TBI was not related to differences in age at AD, but age at injury <25 years old was associated with a 2.3 years earlier age at diagnosis (β = ‐2.34 P = 0.031), which was independent of APOE e4 status. No significant associations were found between TBI history or age at injury and differences in cognitive functioning or NPS.ConclusionThe findings of our study indicate that TBI during childhood, adolescence or early adulthood may influence age of disease onset in AD patients. This underscores previous findings on vulnerability of the brain during critical development and maturation phases and suggest that an early TBI may contribute to lower resilience or higher vulnerability to neurodegenerative changes. TBI history does not seem to affect cognitive characteristics and NPS profiles in AD patients.
Real‐world sleep in Parkinson’s disease predicts cognitive dysfunction.
Authors: Chang Jun Ha , Bhatti Danish , Mieth Teagan , Tartaglia Adam , Rizzo Matthew , Bertoni John M , Merickel Jennifer 
Published: December 2022

AbstractBackgroundSleep dysfunction is signature of Alzheimer’s disease and Parkinson’s disease (PD), and can signify incipient disease, disease risk, and worsen symptoms over time. How real‐world sleep dysfunction relates to patient self‐report of sleep and clinical cognitive dysfunction is poorly understood, partly because self ‐report is impaired in patients with cognitive decline. We monitored real‐world sleep with wearable actigraphy devices in patients with PD to test the hypothesis that objective patterns of sleep dysfunction are associated with worse cognitive performance.MethodTwenty‐nine participants with idiopathic PD (age = 67.44 ± 5.79, 20 males) completed the Montreal Cognitive Assessment (MoCA) and Epworth Sleepiness Scale (ESS) to capture clinical cognitive decline and self‐reported daytime sleepiness. Sleep was monitored for 4‐weeks using wrist‐worn ActiGraphs. Sub‐scores and total scores of MoCA were compared with Total Sleep Time (TST), Sleep Efficiency (SE), Wakefulness After Sleep Onset (WASO), and Sleep Fragmentation Index (SFI) measured by actigraphy, as well as ESS total using a Pearson correlation.ResultWorse sleep fragmentation (SFI), the percentage of awakenings and movements during sleep, predicted worse cognitive impairment overall (MoCA score: r = ‐0.38, p < .05) and delayed recall (r = ‐0.44, p < .05). Reduced sleep time (TST) and worse sleep quality (SE, WASO) did not worsen patient cognitive impairment. Patient self‐report of sleepiness (ESS) did not associate with worse cognitive outcomes.ConclusionThis pilot analysis identifies sleep fragmentation as a key risk factor for cognitive dysfunction in PD. Patient self‐report of sleep may not reliably reflect chronic sleep disruption and related cognitive dysfunction. Results underscore that objective measures of real‐world dysfunction can help inform clinical care and intervention for patients at risk for cognitive decline and dementia.
Metabolic and Cerebrovascular Perturbations in the 5xFAD Mouse Model of Alzheimer’s Disease
Authors: Jullienne Amandine , Szu Jenny , Quan Ryan , Silvola Rebecca , Bedwell Amanda A , Eldridge Kierra , Speedy Rachael , Persohn Scott C , Obenaus Andre , Territo Paul R ,   MODEL AD
Published: December 2022

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium seeks to develop the next generation of AD models based on human data. A popular model of familial AD is the 5xFAD mouse. It is characterized by early amyloid‐β deposition and cognitive decrements. Despite numerous studies, the 5xFAD mouse has not been comprehensively phenotyped for vascular and metabolic aspects over its lifespan.MethodMales and females 5xFAD and WT littermates underwent in vivo 18F‐FDG‐PET imaging at 4, 6, and 12 months to evaluate regional glucose metabolism. A separate cohort of mice (4, 8, 12 months) underwent “vessel painting” that labels all cerebral vessels with a fluorescent dye. Brains were analyzed for vascular characteristics such as vessel and junction density, vessel length, network complexity, number and diameter of collaterals.ResultOur analyses revealed that vessel length, vessel and junction densities increased from 4 to 12 months on the cortical surface in both 5xFAD and WT mice. The number of collateral vessels between the middle cerebral artery (MCA) and the anterior and posterior cerebral arteries decreased with age but interestingly their diameters were significantly increased only in 5xFAD mice. MCA average vessel length was significantly decreased at 8 and 12 months in 5xFAD mice compared to WT; primarily driven by males. Analysis of 18F‐FDG cortical uptake found significant interactions between WT and 5xFAD mice spanning 4‐12 months of age in retrosplenial somatosensory and visual cortices. Broadly, 5xFAD males had increased 18F‐FDG uptake at 12 months of age compared to WT mice. In most cortical regions, female 5xFAD mice had reduced FDG uptake compared to WT across the lifespan. In males these metabolic increases coincided with decreased vessel characteristics.ConclusionThe 5xFAD mouse exhibits AD‐like cognitive deficits with age that are associated with increasing amyloid‐β deposition. No significant differences were found in cortical vascular features although males and females exhibited opposite effects in 18F‐FDG uptake. The MCA supplies blood to large portions of the motor cortex and increased vessel lengths and decreased collaterals along with higher metabolic rates in 5xFAD mice may be related to increasing behavioral deficits via metabolic insufficiency or other mechanisms.
Feasibility and Satisfaction with Online, Livestreaming, Interactive, Group Movement Classes for People with Mild Cognitive Impairment or Mild Dementia and Care Partners
Authors: Nicosia Francesca M , Lee Amanda , Chesney Margaret A , Lee Jennifer Ann , Benjamin Cynthia , Mehling Wolf , Sudore Rebecca L , Barnes Deborah E 
Published: December 2022

AbstractBackgroundPreventing Loss of Independence through Exercise (PLIÉ) is a gentle, in‐person, mind‐body, group movement program for people with dementia (PWD) or mild cognitive impairment (MCI); Paired PLIÉ includes dyads of PWD and care partners (CPs). We previously found that PLIÉ and Paired PLIÉ improve physical, cognitive, social, and emotional well‐being. This study assessed feasibility and satisfaction with an online version called Moving Together.MethodStudy participants were recruited through previous in‐person PLIÉ/Paired PLIÉ classes, caregiver support groups, social media, and word‐of‐mouth. Inclusion criteria were: ≥18 years old, live in U.S., be a PWD (typically with a CP) or have MCI (with or without CP), and be willing and able to participate in online Moving Together classes for 1 hour, 2 days/week for 12 weeks during the study period. We assessed feasibility based on program completion and class attendance and satisfaction using a post‐program evaluation survey with quantitative and open‐ended questions.ResultA total of 39 people (18 PWD, 7 MCI, 14 CP) participated in 4 classes. PWD/MCI were 78 ± 16 years old, 56% female and 73% non‐Hispanic white. CPs were 66 ± 16 years old, 80% women, and 61% non‐Hispanic white. Nearly half (44%) had previously participated in‐person. Thirty participants (77%) completed the 12‐week program, of whom 24 (80%) completed the evaluation survey. Participants attended 75% ± 29% of classes. Ninety‐six percent (n = 23) rated the program as excellent (n = 19) or good (n = 4), and 88% (n = 21) were highly likely to recommend the program to others (scores of 8‐10 on 10‐point scale). Qualitative analyses revealed participant‐reported benefits for PWD, MCI and CPs in the domains of social connection (“camaraderie,” “like a family”), emotional well‐being (“happier,” “less stressed”), physical function/state (“balance has improved,” “more range‐of‐motion,” “stronger,” “energized,” “relaxed”), cognitive function (“more focus,” “learning new things”) and present‐centered body awareness (“more conscious of breathing patterns”). In addition, PWD/MCI experienced improvements in self‐concept/acceptance (“less immediate shame and more confidence”), and CPs reported improvements in caregiving efficacy (“greater purpose,” “more comfortable”).ConclusionThe online Moving Together program is feasible for people with dementia or mild cognitive impairment and care partners. Participants report high satisfaction and positive outcomes.
Validation of the ki:e SB‐C a Novel Digital Speech Biomarker for Cognition in a Dutch Memory Clinic Population
Authors: Linz Nicklas , Mallick Elisa , Mina Mario , Possemis Nina , König Alexandra , Huurne Daphne B.G. ter , Ramakers Inez H.G.B. , Tröger Johannes 
Published: December 2022

AbstractBackgroundProgressive cognitive decline is the cardinal behavioral symptom in most dementia‐causing diseases such as Alzheimer’s disease. Whereas classic neuropsychological tests often have excellent psychometric properties to measure cognitive decline in dementia, there are scenarios in which they are less suitable. Speech‐based digital biomarkers can be deployed remotely and extracted in a highly automated fashion allowing solutions to scale. We present the validation of a novel digital Speech Biomarker for Cognition (SB‐C) in a Dutch memory clinic population containing patients with Mild Cognitive Impairment (MCI) and age‐ as well as education‐matched participants with Subjective Cognitive Decline (SCD).MethodThe ki:e SB‐C is a novel speech‐based cognitive composite score. The presented validation results are based on a sample that was not used when developing the SB‐C. Validation data has been collected from two age‐ and education‐matched groups: Normal Cognition but subjective cognitive decline (SCD; n = 48, 15 F), MCI (n = 48, 18 F). We automatically extract the SB‐C from SVF and AVLT speech recordings using our proprietary speech analysis pipeline including automatic speech recognition and feature extraction. Recordings were collected from a Dutch memory clinic population containing MCI and SCD participants. We performed (1) analytical and (2) clinical validation. For (1) we performed Spearman rank correlation between SB‐C score and anchor score Mini Mental State Examination (MMSE) to show that the algorithm is correctly measuring the concept of interest cognition. For (2) we performed a non‐parametric Kruskal‐Wallis test to compare SB‐C scores of both NC and MCI groups.ResultThe biomarker score SB‐C and MMSE were strongly correlated (r = 0.61, p < 0.001), such that lower MMSE scores are reflected in lower biomarker scores (compare also figure 1). Additionally, there was a very significant group difference for the SB‐C biomarker score between the NC and MCI group (NC > MCI; χ2 = 26.461 (1), p < 0.001).ConclusionThe ki:e SB‐C is a reliable score for cognition, showing convergent validity with the MMSE and separating well between MCI and SCD populations. The availability of valid digital speech biomarkers for cognition has great potential for decentralized clinical trials in dementia aetiologies and beyond.
Amyloid‐associated increases in soluble tau is a key driver in accumulation of tau aggregates and cognitive decline in early Alzheimer
Authors: Binette Alexa Pichet , Franzmeier Nicolai , Spotorno Nicola , Ewers Michael , Brendel Matthias , Biel Davina , Strandberg Olof , Janelidze Shorena , Palmqvist Sebastian , Mattsson‐Carlgren Niklas , Smith Ruben , Stomrud Erik , Ossenkoppele Rik , Hansson Oskar 
Published: December 2022

AbstractBackgroundFor optimal design of anti‐amyloid‐β (Aβ) and anti‐tau clinical trials, it is important to understand how Aβ and soluble phosphorylated tau (p‐tau) relate to the accumulation of tau aggregates assessed with positron emission tomography (PET) and subsequent cognitive decline across the Alzheimer's disease (AD) continuum.MethodWe included 327 participants from the Swedish BioFINDER‐2 cohort with cerebrospinal fluid (CSF) p‐tau217, Aβ‐PET, longitudinal tau‐PET, and longitudinal cognition. The main groups of interest were Aβ‐positive non‐demented participants and AD dementia patients (Table 1 and Figure 1), and analyses were conducted separately in each group. First, we investigated how soluble p‐tau217 and regional Aβ‐PET were associated with tau‐PET rate of change across the 200 brain parcels from the Schaefer atlas. We also tested the mediating effect of p‐tau217 between Aβ‐PET and tau‐PET change. Second, we investigated how soluble p‐tau217 and tau‐PET change related to change in cognition, and mediation between these variables.ResultIn early AD stages (non‐demented participants), increased concentration of soluble p‐tau217 was the main driver of accumulation of insoluble tau aggregates across the brain (measured as tau‐PET rate of change), beyond the effect of regional Aβ‐PET and baseline tau‐PET (Figure 2A‐C). Further, averaged across all regions, soluble p‐tau217 mediated 54% of the association between Aβ and tau aggregation (Figure 2D). Higher soluble p‐tau217 concentrations were also associated with cognitive decline, which was mediated by faster increase of tau aggregates (Figure 3). Repeating the same analyses in the AD dementia group, results were different. In late stage of AD, when Aβ fibrils and soluble p‐tau levels have plateaued, soluble p‐tau217 was not associated with accumulation of tau aggregates beyond baseline tau‐PET (Figure 4A), and cognitive decline was driven by the accumulation rate of insoluble tau aggregates and not soluble p‐tau217 (Figure 4B‐C).ConclusionSoluble p‐tau is a main driver of tau aggregation and future cognitive decline in earlier stages of AD, whereas tau aggregation accumulation is more likely an important driver of disease in later stages. Overall, our data suggest that therapeutic approaches reducing soluble p‐tau levels might be most favorable in early AD.
Functional networks underlying the association between tau pathology and memory
Authors: Ziontz Jacob , Harrison Theresa M. , Adams Jenna N. , Chen Xi , Cassady Kaitlin , Zhuang Kailin , Jagust William J. 
Published: December 2022

AbstractBackgroundTau pathology is associated with impaired episodic memory (EM) in both aging and Alzheimer’s disease (AD), but the mechanisms by which tau and memory are linked remain unclear. We hypothesized that strength of an EM‐defined functional brain network would mediate the relationship between tau and memory performance.MethodResting state fMRI was collected in 120 cognitively normal older adults from the Berkeley Aging Cohort Study (77.6 ± 6.4 years, 57.5% female), with a subset of 94 individuals receiving tau‐PET with 18F‐Flortaucipir and Aβ‐PET with 11C‐PiB. Functional connectivity (FC) for each ROI‐ROI pair of a 246‐region whole brain atlas was computed, yielding 30,000+ unique connections. LASSO regression of each of these values against an EM composite measure was used to select a sparse subset of connections related to greater EM performance. Overall strength of this network was computed as the sum of FC values for all selected ROI‐ROI pairs. Linear regression and causal mediation analyses were used to assess relationships between network strength and AD pathology.ResultThe EM‐defined network of 51 ROI‐ROI connections comprised limbic, temporal, and frontal regions (Figure 1). Adjusting for age and sex, reduced overall network strength was associated with an interaction between greater global Aβ and tau, both in an inferomedial temporal cortex meta‐ROI (b=‐26.97,p=.013; Figure 2a), and entorhinal cortex (b=‐14.01, p=.034; Figure 2b). For control analyses using an executive function‐defined network, overall network strength was not related to an Aβ‐tau interaction in the meta‐ROI (b=‐9.894, p=.415) or entorhinal cortex (b=‐6.206, p=.403; Figure 2c‐d). Causal mediation analysis revealed the effect of meta‐ROI tau on EM performance was mediated by the overall strength of the EM‐defined network (b=‐0.802, p=.017; Figure 3a), but not the executive function‐defined control network (b=‐0.098, p=.424; Figure 3b).ConclusionUsing LASSO regression to select a sparse subset of functional connections related to EM in older adults, we found that reduced strength of this network was associated with the coincidence of greater tau and Aβ pathology. Alterations in behaviorally‐defined networks thus are reflective of AD pathology and appear to be a key factor in understanding its link to cognitive function.
Neuropathological evidence that the association between APOE‐e4 genotype and higher medial temporal lobe tau burden is mediated by higher local amyloid‐β levels
Authors: Salvadó Gemma , Vogel Jacob W , Beach Thomas G , Serrano Geidy E , Schneider Julie A , Ossenkoppele Rik , Hansson Oskar 
Published: December 2022

AbstractBackgroundEvidence from previous PET imaging studies suggests that increased neocortical tau seen in APOE‐ε4 carriers can be explained by the higher levels of neocortical amyloid‐β (Aβ) pathology also seen in this group. However, these studies also suggest an amyloid‐independent association between APOE‐ε4 and medial temporal lobe (MTL) tau. Using neuropathological data, we investigated whether amyloid‐β in the MTL, which is difficult to accurately measure with PET, may fully mediate the association between APOE‐ε4 carriership and MTL tau burden.MethodAmyloid‐β and tau pathology in MTL and neocortical areas have been measured in a total of 2,704 individuals from two independent neuropathological datasets (Arizona Study of Aging and Neurodegenerative Disorders, Brain and Body Donation Program, n=1,117 and ROSMAP, n=1,587; Table 1). Regression models were used to investigate the associations between APOE‐ε4 carriership and neocortical and local (MTL) amyloid‐β on MTL tau, adjusting for age, sex and presence of co‐pathologies. Based on these results, we also tested whether local (MTL) amyloid‐β mediated the association between APOE‐ε4 carriership and MTL tau.ResultSupporting results from previous studies, APOE‐e4 carriers showed higher tau burden in the MTL (p<0.001) when amyloid‐β was not included in the model in both datasets. In independent models, both local and neocortical amyloid‐β were associated with MTL tau, with local amyloid‐β showing a stronger association with MTL tau in both datasets (Arizona: βMTL=0.93 vs. βneoc=0.76; ROSMAP: βMTL=0.42 vs. βneoc=0.40). When both measures were included in the model, local amyloid‐β also showed a stronger association with MTL tau in ROSMAP (βMTL=0.28 vs. βneoc=0.19). In the Arizona dataset, neocortical amyloid‐β effect became non‐significant (p=0.252) when local amyloid‐β was also included in the model. Finally, with mediation analyses we observed that MTL amyloid‐β fully mediated the APOE‐ε4 effect on MTL tau in both datasets (Figure 1). All statistics are reported in Table 2.ConclusionIn two large neuropathological datasets, we showed that the association between APOE‐ε4 genotype and higher medial temporal lobe tau burden is mediated by higher local amyloid‐β levels. This finding contradicts some previous imaging literature, where only global amyloid‐β burden was considered.