bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toronto dementia research alliance (TDRA) dementia clinical‐research platform: An example of research embedded into clinical care
Authors: Tang‐Wai David F. , Strother Stephen C. , Pugh Bradley , Spring Robyn , Vica Carmina , Nourhaghighi Nima , Gee Tom , Pisterzi Luca , Greenberg Barry , Coahran Margaret , Apatsidou Areti , Ding Jane , Kumar Sanjeev , Black Sandra E. , Freedman Morris 
Published: December 2020

AbstractBackgroundDementia is arguably the greatest looming global public health challenge facing today’s society and represents an international crisis as the number of affected persons will triple by 2050. Contributing to morbidity of dementia is the presence of combined pathologies, such as Alzheimer’s disease (AD), cerebrovascular disease (CVD) and Parkinson’s disease (PD). To address this challenge, the TDRA ‐ a collaboration of the University of Toronto’s Faculty of Medicine with four University‐affiliated tertiary memory clinics ‐ created an electronic platform for research studies embedded in clinical care through development of a unified approach for diagnosis and charting of the natural history of pure and mixed dementias, along with the impact of co‐occurring disorders.MethodA detailed clinical intake form and cognitive testing (for mild‐to‐severe impairment) were created through a collaboration among behavioural neurologists, geriatricians and geriatric psychiatrists. These measures are captured electronically at point‐of‐care and, simultaneously, the deidentified information uploaded to a central research server (see Figure 1).ResultAfter approximately 1 year since collecting information, 1182 new patients (622 women; 560 men) have been evaluated – 119 AD; 76 concussion; 20 CBS; 8 delirium; 2 MBI, 278 MCI, 42 mixed AD and CVD; 16 PSP; 1 MSA‐P, 16 PD, 17 PD‐MCI, 21 PDD; 32 DLB; 24 bvFTD; 7 lvPPA, 13 nfPPA; 12 svPPA, 136 with primary and/or co‐morbid psychiatric disease; 165 subjective cognitive impairment; 93 VCI; 18 normal cognition; and 18 dementia NYD. Each of these patients have some demographic and clinical details, such as comorbid psychiatric and/or medical disorders, and cognitive testing obtained for research.ConclusionThe TDRA Dementia Clinical‐Research Platform is a practising example of research embedded into clinical care with over 1000 new patients with diverse diagnoses evaluated in 1 year and may represent the types of dementia seen in Toronto and surrounding areas. A letter, based on the clinical intake form, is being programmed to send back to the referring physician and will enhance clinical care, along with scores and graphic display of the cognitive testing results.
Serum adiponectin and methylation of adiponectin gene promoter in peripheral blood of the patients with Alzheimer’s disease and vascular dementia
Authors: Kaiyrlykyzy Aiym , Tsoy Andrey , Umbayev Bauyrzhan , Olzhayev Farkhad , Alzhanova Dinara , Zhussupova Alma , Zhumalin Aibek , Masoud Abdul‐Razak , Askarova Sholpan 
Published: December 2020

AbstractBackgroundThere is increasing body of evidence indicating that adiponectin (APN), a protein hormone produced mainly by white adipose tissue, may be an independent risk factor for all‐cause dementias and Alzheimer’s disease (AD). A number of studies demonstrated that concentration of APN was increased in plasma of patients with mild cognitive impairment (MCI) and AD compared to healthy individuals. In contrast, some studies did not find significant changes in plasma adiponectin in AD patients, or even demonstrated lower plasma level of APN in MCI and AD compared to controls. These controversial data indicate that more studies are needed to reveal an association between plasma adiponectin and dementia. In the present study we have evaluated APN level in blood and analyzed APN gene methylation in patients with AD and vascular dementia (VD).MethodBlood samples were obtained from the patients with AD (n =26), VD (n=31) and cognitively normal individuals (n =44). We measured serum adiponectin level using ELISA kit; APN gene methylation in blood was analyzed using bisulfite modification of DNA protocol followed by methylation specific PCR.ResultAnalysis of serum adiponectin levels showed a 3‐fold increase in participants with AD (p<0.001) and VD (p<0.001) compared to the control group. 15 out of 57 (26.3%) of the samples in dementia group vs 1 out of 44 (2.3%) of the control samples had a methylated adiponectin gene promoter (p=0.001). Methylation of the adiponectin gene promoter in peripheral blood occurred with relatively same frequency in individuals with AD and VD, 23% and 29%, respectively (p=0.765). In AD patients serum adiponectin level was almost twice as high in samples in which methylation was observed (p=0.0294).ConclusionOur data demonstrated that in people suffering from AD and VD there was an increase in the levels of serum adiponectin and amplified methylation of adiponectin gene promoter in peripheral blood. These findings may serve as a basis for the development of prognostic biomarkers of AD and VD. Nevertheless, more data collection is necessary for further analysis and interpretation.
Cerebral hemodynamic responses of subjective cognitive decline evoked by loaded N‐back tasks
Authors: Du Wenying , Zhang Yaoyu , Gao Jiahong , Han Ying 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) is a high risk for Alzheimer’s disease. The physiological mechanisms of SCD is largely unknown. Most of the existing studies made their observations during the resting state of the brain. How the SCD group performs differently from the normal controls (NC) during functional tasks is less studied. This study compared the responses of SCD and NC evoked by loaded working memory tasks. The results of this study help clarify the underlying hemodynamic mechanisms of SCD.Methods15 NC (8 females) and 23 SCD subjects (14 females) participated in the study. Table 1 shows the biographical and behavioral data of the two groups. All subjects participated block‐designed 0‐back, 1‐back, 2‐back and 3‐back working memory tasks. Followed by the N‐back tasks, each subject underwent a hypercapnic challenge during which the subject breathed a gas mixture (5% CO2, 20% O2, 75%N2) through a non‐rebreather mask. A pulse sequence which simultaneously acquires cerebral blood volume (CBV), cerebral blood flow (CBF), blood oxygen‐level dependent (BOLD)‐weighted signals was implemented on a 3.0 T GE MR750 system. At the group level, holding sex, age and education as covariates, a general linear model was applied to compare the above parameters between the two groups, and a partial correlation test was performed to relate the imaging results with the behavior data. P < 0.05 was considered statistically significant.ResultsThe group averages of δCBV, δCBF, δBOLD and δCMRO2 evoked by 1‐, 2‐ and 3‐back, with respect to 0‐back, in the frontal cortex were displayed in Figure 1. In general, all parameters show a load‐dependent effect, where 1‐back caused minimum signal changes. Among all parameters, δCBF evoked by 3‐back, with respect to 0‐back, was significantly lower (p = 0.04) in the SCD group compared to the NC group. None of the other parameters showed statistical differences between the two groups. In addition, δCBF at 3‐back was found to be significantly correlated with the MoCA (p = 0.04) and AFT (p 0.03) scores of the subjects.ConclusionThis study may help understand the physiological mechanisms and develop early diagnostic strategies of SCD.
Plasma amyloid‐β dynamics are regulated by the sleep‐wake cycle
Authors: Zhao Beiyu , Liu Chenyu , Wang Liang , Wei Meng , Dang Jingxia , Qu Qiumin 
Published: December 2020

AbstractBackgroundIt has been reported that sleep is an important physiological process and conducive to the elimination of brain metabolites and the recovery of brain function. Growing evidence suggested that sleep disorders were related to increased risk of AD and Aβ accumulation in the brain. Although peripheral Aβ clearance is associated with brain Aβ deposition, but the relationship between sleep‐wake cycle and plasma Aβ levels is unclear.MethodThirty cognitively normal healthy adults (aged 29.07 ± 8.12), sixteen males (53.33%), were recruited. Participants underwent normal sleep and peripheral blood samples were collected every three hours between 20:00 and 8:00 the next day. Plasma Aβ40, Aβ42, total tau, phosphorylated tau 181 (P‐tau), soluble low‐density lipoprotein receptor‐related protein (sLRP1) and soluble receptors for advanced glycation end products (sRAGE) levels were measured using ELISA kits.ResultPlasma Aβ40 concentration at 5:00 decreased significantly compared with plasma level at 23:00 (p=0.041), and there is a dynamic tendency of decreasing after sleep onset and increasing after awake, which is in accordance with the sleep‐wake cycle. Furthermore, Aβ40 and Aβ42 levels were positively correlated with plasma sLRP1 (Aβ40: r=0.1791, p=0.0283; Aβ42: r=0.1780, p=0.0293). However, there was no significant dynamic change in Aβ42, Tau, P‐tau, Tau, sLRP1 and sRAGE levels in twelve hours.ConclusionPlasma Aβ40 dynamics are regulated by the sleep‐wake cycle, and it may play a positive feedback regulating role in sLRP1 level.
The effect of digital reminiscence therapy on the verbal communication of people with dementia
Authors: Park Kyongok , Moon SeolHwa 
Published: December 2020

AbstractBackgroundVerbal communication is the basic function for social interaction. People with dementia (PWDs) experience a deterioration in verbal communication function, and this restricts social engagement, and could lead to social isolation. Reminiscence therapy is known to affect emotion, cognition, and behavioral disturbance for PWDs. The effect of digital reminiscence using digital material or equipment for PWDs has also been reported recently. However, it is not clear whether there is an effect of digital reminiscence therapy on verbal communication function for PWDs. Therefore, this study aims to test the effectiveness of digital reminiscence therapy on verbal communication for PWDs.MethodThis study was a randomized, controlled trial that was conducted at nine daycare centers from January to June 2019 (registration number: KCT0003446). The Android application was developed for digital reminiscence therapy. Digital reminiscence or storytelling therapy was performed in each group for eight sessions for four weeks. Out of the 49 female participants, 25 were randomly assigned to the digital reminiscence therapy group, and 24 were randomly assigned to the storytelling (control) group, without using digital materials. The video files of the sessions were analyzed with Noldus Observer XT 14.0 software. The Holden communication scale, verbal engagement, and the number of words used during the therapy session were measured to evaluate the verbal communication function of PWDs at the first session (T1), and the last session (T2). A paired T test analyzed differences in outcomes between the sessions and groups.ResultThe mean value of the Holden communication scale was significantly decreased in the digital therapy group at the last session (t = 2.663, p = .015). However, there was not a significant decreasing of the variable in the control group at the last session (t= ‐ .042, p = .967).ConclusionThe results of this study showed that digital reminiscence therapy had an effect on the verbal communication function of PWDs. Therefore, the verbal communication function maintained or increased by the digital reminiscence therapy will assist PWDs in interacting with others and help to decrease social isolation. Eventually, digital reminiscence therapy will contribute to increasing the quality of life of PWDs.
Longitudinal flortaucipir accumulation is spatially distinct across baseline tau burden stages: Summary from three phase 2/3 interventional trials in Alzheimer’s disease
Authors: Shcherbinin Sergey , Higgins Ixavier A. , Lu Ming , Pontecorvo Michael J. , Lo Albert C. , Sims John R. 
Published: December 2020

AbstractBackgroundTo date, regional patterns of the longitudinal tau accumulation in Alzheimer’s Disease (AD) have been examined in very few studies with limited sample sizes. We combined data from three phase 2 or 3 interventional trials to illustrate regional patterns of longitudinal flortaucipir accumulation.MethodEXPEDITION3 (NCT01900665), NAVIGATE‐AD (NCT02791191) and AMARANTH (NCT02245737) were double‐blind, placebo‐controlled multi‐center trials that enrolled amyloid‐positive patients with early or mild AD dementia. Longitudinal changes for flortaucipir were examined for N=208 placebo participants who underwent 8‐16 month follow‐up (scheduled or early discontinuation) flortaucipir scans. Flortaucipir scans were pooled across the three trials and divided into four stages corresponding to very low, low, medium, and high baseline global neocortical tau SUVR using pre‐determined cut‐points (Pontecorvo et al, 2019). A stage‐wise annualized percent change (APC) and mean‐standard deviation (SD) ratio (MSDR) of longitudinal tau accumulation were examined for 17 Automated Anatomical Labeling (AAL) atlas‐based bilateral cortical regions and a composite neocortical region of interest (ROI).ResultOur analysis suggested a dependence of the regional longitudinal tau accumulation profile on the global baseline tau burden at a group level. In the lowest baseline SUVR group (N=36), minimal accumulation was observed in the composite ROI (APC=0.04%, MSDR=0.01) and the inferior temporal region (APC=1.00%, MSDR=0.41) showed the strongest tau signal increase. At low (N=42) and medium (N=63) baseline levels, we found a relatively wide‐spread and spatially uniform accumulation with an APC of 2‐3% in the majority of the cortical regions and composite ROI. For patients with a high global baseline burden (N=67), tau increased in all considered frontal regions (APC ≥ 3.95%, MSDR>0.42) which exceeded accumulations in the composite ROI (APC=2.82%, MSDR=0.32).ConclusionFor the amyloid positive early‐to‐mild AD population, we found different cross‐sectional tau deposition and different regional longitudinal profiles across four baseline tau stages. Performing tau‐based screening might enroll more pathologically homogeneous populations in interventional trials and permit utilization of optimal measures of tau change as outcomes.
Longitudinal aortic stiffness is associated with brain microstructure and cognition: A voxel‐wise magnetic resonance imaging study
Authors: Suri Sana , Chiesa Scott T , Zsoldos Enikő , Filippini Nicola , Mackay Clare , Griffanti Ludovica , Mahmood Abda , Singh‐Manoux Archana , Shipley Martin J , Brunner Eric , Kivimaki Mika , Deanfield John , Ebmeier Klaus P 
Published: December 2020

AbstractBackgroundAortic stiffness, assessed by carotid‐femoral pulse wave velocity (PWV), is closely linked with hypertension, heart disease and stroke. Recent research has suggested that rapid aortic stiffening may also be a risk factor for cognitive decline and dementia. However, the age of onset of this risk and its underlying brain physiology is unknown. We examined whether aortic stiffening over a 5‐year period in mid‐life affects later‐life brain structure and cognition in community‐dwelling adults.MethodData from 544 participants from the Whitehall II Imaging Sub‐study were analysed. Aortic PWV was measured at baseline in 2007‐09 (mean age 63.92±5.23) and at a 5‐year follow‐up visit in 2012‐13 (mean age 67.99±5.25) using applanation tonometry (SphygmoCor, AtCor Medical, Australia). After the latter visit, they also received cognitive tests and a 3T brain MRI scan (2012‐2016, mean age 69.82±5.23). Voxel‐based morphometry and tract‐based spatial statistics were used to extract grey matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and white matter hyperintensity (WMH) volumes. Baseline and follow‐up arterial stiffness were entered as predictors of MRI and cognitive outcomes in two separate general linear models, each adjusting for age, sex, education, mean arterial pressure, body mass index, socio‐economic status, scanner model, and follow‐up time interval.ResultHigher aortic stiffness at baseline was associated with significantly poor performance in semantic fluency (category ‘animals’, B(SE)=‐0.42(0.15), Bonferroni‐corrected p<0.008) and short‐term verbal memory (immediate recall on the Hopkins Verbal Learning Test‐R, B(SE)=‐0.36, (0.12), Bonferroni‐corrected p<0.008) at the time of the scan. Follow‐up aortic stiffness was associated with significantly lower FA and higher MD in widespread brain areas including the corpus callosum, corona radiata, cingulum, and superior longitudinal fasciculus (p<0.05, corrected for voxel‐wise comparisons). No significant associations with GM or WMH were observed.ConclusionElevated aortic stiffness after age 60 is associated with poor WM microstructural integrity and cognitive performance in older age independently of standard vascular risk factors, likely due to increased transmission of pulsatile energy to the delicate cerebral microvasculature. To offer cognitive benefit in older age, strategies to prevent arterial stiffening may be more effective in midlife than in later‐life.
Cerebrospinal fluid tau biomarkers in the prediction and concordance of neurofibrillary tangle and amyloid pathology
Authors: Ashton Nicholas J , Benedet Andréa Lessa , Pascoal Tharick A , Kvartsberg Hlin , Karikari Thomas K , Schöll Michael , Stoops Erik , Francois Cindy , Vanmechelen Eugeen , Mathotaarachchi Sulantha , Savard Melissa , Therriault Joseph , Chamoun Mira , Zetterberg Henrik , Rosa‐Neto Pedro , Blennow Kaj 
Published: December 2020

AbstractBackgroundCerebrospinal fluid (CSF) measures of tau (p‐tau181 and t‐tau) are central to the research diagnostic criteria for Alzheimer’s disease (AD). Nevertheless, alternative tau phosphorylation sites or tau fragments merit further evaluation to better index neurofibrillary tangle (NFT) and amyloid‐β (Aβ) pathology.MethodWe evaluated 168 participants from the TRIAD cohort (young controls, cognitively normal controls (CN), mild cognitive impairment, frontotemporal dementia and AD patients). LUMIPULSE® G1200 (Fujirebio) was used to measure CSF p‐tau181 and t‐tau. CSF p‐tau231 was quantified using a prototype ELISA assay (ADx NeuroSciences). CSF p‐tau217 and tau368 was measured using an in‐house Simoa assay (University of Gothenburg). For PET ([18F]MK6240 and [18F]AZD4694), standard uptake value ratios (SUVR) were determined using the cerebellar and cerebellar cortex as reference tissue, respectively. Finally, ROC curves were generated to investigate the predictive power of the CSF biomarkers.ResultAll CSF p‐tau biomarkers equally associated with [18F]MK6240 (r>0.51), while CSF p‐tau231 correlated more to [18F]AZD4694 (r=0.815) than other tau biomarkers. ROC curves revealed p‐tau biomarkers accurately detected Braak I‐II (AUC>0.905) and III‐IV positivity (AUC>0.940), with p‐tau217 significantly out performing p‐tau231 and p‐tau181 at both stages. Tau368/t‐tau ratio was the superior biomarker in the prediction of Braak V‐VI positivity. P‐tau217 and p‐tau231 demonstrated high accuracy in predicting Aβ positivity (ROC>0.950). This was significantly better than p‐tau181 (p‐tau217, P<0.01; p‐tau231, P<0.001). Prediction of Aβ positivity was also high at the pre‐symptomatic stage for p‐tau231 (ROC>0.9) and again was significantly superior to p‐tau181 (P<0.01). All p‐tau biomarkers demonstrated full concordance (CSF‐/PET‐) with [18F]MK6240 and [18F]AZD4694 for young controls and FTD subjects. P‐tau217 and p‐tau231 demonstrated high concordance with [18F]MK6240 and discordant cases were restricted to the CSF+/PET‐ quadrant (Figure 1). In the same manner, CSF p‐tau217 and p‐tau231 demonstrated the highest concordance with [18F]AZD4694, although subjects were observed in both discordant quadrants (Figure 2).ConclusionAll CSF p‐tau biomarkers relate to NFT pathology to the same degree, however, tau368/t‐tau seemingly characterises NFT pathology at an advanced stage. CSF p‐tau217 and p‐tau231 are better predictors of Aβ pathology, with p‐tau231 a stronger predictor of Aβ pathology at the pre‐symptomatic stage.
A video feedback intervention for cognitively impaired older drivers
Authors: Ott Brian R , Papandonatos George D , Burke Erin M , Erdman Donna , Carr David B , Davis Jennifer D 
Published: December 2020

AbstractBackgroundThe goals of this study were to demonstrate that in‐car video technology can effectively detect unsafe driving events in cognitively impaired older adults, and that providing feedback about these events to the drivers and their family members can lead to a reduction in the frequency and severity of unsafe driving behaviors.MethodsUnsafe driving events (UDE) were triggered by g‐forces leading to capture of a video record that was then transmitted wirelessly to a remote office where each event was analyzed, categorized, and scored for safety demerit points. During the baseline phase (3 months), all participants were monitored with no feedback. During the intervention phase (4‐6 months), half of the participants and their family members were randomly assigned to receive a weekly progress report in the mail along with a DVD of recorded unsafe driving events with recommendations. They also had continuous access to the videos and scores on a web site. The other half of the participants continued with monitoring only. During the post‐intervention monitoring phase (7‐12 months), there was continued monitoring of all participants, but no further feedback.ResultsOf 51 drivers enrolled at baseline (34 with CDR 0.5 and 17 with CDR 1; mean MMSE = 24.35±3.03), 50 drivers completed baseline monitoring and were randomized to monitoring or intervention. During the intervention, UDE frequency per 1,000 miles was reduced by 21% from baseline in the feedback group (Rate Ratio= 0.79, 95% CI=.53‐1.17), while remaining approximately constant in the monitoring group (Rate Ratio=1.02, 95% CI=.69‐1.52). UDE severity score per 1,000 miles was reduced by 48% from baseline in the feedback group (Rate Ratio=0.52, 95% CI=.21‐1.27), but increased by 37% in the monitoring group (Rate Ratio=1.37, 95% CI=.67‐2.83). No major accidents or injuries occurred throughout the course of the study.ConclusionsThese results suggest the potential to improve driving safety among older drivers with cognitive impairment using a behavior modification approach aimed directly at problem behaviors detected in their natural driving environment using g‐force triggered video technology.