bluuebunny/crossref_metadata_2025_split huggingface dataset:
The validity and reliability of the digital Ruff Figural Fluency Test (RFFT) in the general adult population
Authors: Vrijsen Joyce , van Erpecum Carel‐Peter , Niebuur Jacobien , Smidt Nynke 
Published: December 2020

AbstractBackgroundThe Ruff Figural Fluency Test (RFFT) is a valid pencil‐and‐paper test for evaluating cognitive functioning in the general population. The assessment of the pencil‐and‐paper‐RFFT is time‐consuming and requires training of raters. We developed a digital‐RFFT which can be filled in by people independently on an Ipad, after which RFFT patterns are automatically processed and stored. We aimed to investigate the validity and reliability of the digital‐RFFT in the general population.MethodStratified randomization (based on age, gender, and education) was used to allocate participants either to the digital‐RFFT or the pencil‐and‐paper‐RFFT. After the first test, the other test was repeated (cross‐over). The number of unique designs and perseverative errors of the pencil‐and‐paper‐RFFT and digital‐RFFT were assessed by an computerized algorithm (automatic) and by two independent trained human raters (criterion standard). For the statistical analysis, we used Intraclass correlation coefficients(ICC), sensitivity, specificity, %agreement, weighted Kappa, and Bland Altman plots, including limits‐of‐agreement(LoA).ResultsThe study population comprised 96 participants (58% women; mean(SD) age 40(15)years). The mean(SD) number of unique designs was 84.2 (26.0) (automatic assessment) and 85.3 (26.2) (human assessment) for the digital‐RFFT and 91.3 (22.7) for the pencil‐and‐paper‐RFFT. The median number(IQR) of perseverative errors was 4(2‐7) (automatic assessment) and 4.5(2‐8) (human assessment) for the digital‐RFFT and 4.5(2‐7.5) for the pencil‐and‐paper‐RFFT. The percentage agreement (kappa) between the two human raters for the digital‐RFFT and pencil‐and‐paper‐RFFT was 0.94(0.90) and 0.94(0.81), respectively. ICC between human assessment and automatic assessment of the digital‐RFFT (unique designs) was 0.988(95%CI:0.981‐0.992); sensitivity and specificity was 0.98 and 0.96 respectively; mean difference(95%CI):‐1.12(‐1.92,‐0.33); 95%Limits‐of‐Agreement ‐8.75,6.51). The ICC between digital‐RFFT and pencil‐and‐paper‐RFFT was 0.53(95%CI 0.37,0.67). When starting with the paper‐and‐pencil‐RFFT, this ICC was 0.73 (95%CI:0.34,0.87). The mean difference (unique designs) between the digital‐RFFT and pencil‐and‐paper‐RFFT was ‐7.09 (95%CI ‐11.8 to ‐2.38 (95%limits‐of‐agreement: ‐52.12, 37.94). This was due to unclear instructions (i.e. complex examples) that were given on the Ipad (digital‐RFFT) and learning effect.ConclusionsAlthough small and systematic differences between human assessment and automatic assessment of the digital‐RFFT were found, we conclude that the digital‐RFFT is a valid test to assess cognitive functioning among the general population if instructions of the digital‐RFFT are improved.
Effects of bibliotherapy on improving caregiving appraisal and coping among informal caregivers of people with dementia: A pilot randomized controlled trial
Authors: Wang Shanshan , Cheung Daphne Sze Ki , Leung Angela 
Published: December 2020

AbstractBackgroundThe number of people with dementia is increasing worldwide, and the majority are cared for by informal caregivers in home settings. Both positive and negative caregiving outcomes have been found among informal caregivers, the essential determinant was caregiving appraisal. Improving their caregiving appraisal is important for both the caregiver and care‐recipient’s health. However, as professional support for informal caregivers are limited, self‐help approaches are needed. Bibliotherapy, a self‐help intervention requiring minimal professional support, has been proved to be effective on improving caregiving appraisal in other populations, the effect on dementia caregivers is yet to be explored. Objectives: To explore the efficacy of bibliotherapy on improving caregiving appraisal and coping among informal caregivers of people with dementia.MethodA two arm randomized controlled trial was conducted in Zhengzhou, China. Participants were randomized to either the intervention group, receiving 8 weekly bibliotherapy sessions at home without withdrawing from usual care; or the control group, receiving usual care from the community health centers. Assessors were blinded to group allocation. Generalized estimating equation was used for data analysis.ResultsSixty participants were recruited, and 24 out of 30 participants in the intervention group finished the intervention. Bibliotherapy had significant group (Wald χ2=4.98, p=0.026), time (Wald χ
2=15.27, p<0.001) and group‐by‐time interaction effects (Wald χ2=16.51, p<0.001) on the total score of caregiving appraisal. In terms of the subscales, there were significant time effects on subjective burden (Wald χ2=8.81, p=0.003), caregiving impact (Wald χ
2=11.31, p=0.001) and caregiving mastery (Wald χ
2=11.74, p=0.001), and significant group effects on caregiving satisfaction (Wald χ
2=7.39, p=0.007). The group‐by‐time interaction was significant on all the subscales (Wald χ2=5.38‐10.89, p=0.001‐0.020). Bibliotherapy also had significant group (Wald χ2=10.93‐15.24, p<0.001), time (Wald χ
2=10.99‐33.02, p<0.001) and group‐by‐time interaction (Wald χ
2=8.91‐17.80, p=0.001‐0.003) effects on the total score of coping and the positive coping subscale. However, the effects on negative coping were not significant (Wald χ
2=0.53‐3.17, p=0.075‐0.467). No adverse events were found.ConclusionBibliotherapy had significant preliminary effects on improving caregiving appraisal and positive coping. The effect on negative coping is still limited. Future randomized controlled trials with larger sample sizes and long‐term follow‐ups are encouraged.
Dual‐task gait and cognitive performance in midlife type 2 diabetes mellitus (T2DM): Baseline data from ENBIND
Authors: Dyer Adam H , McKenna Louise , Gamage Githmi , Killane Isabelle , Woods Conor , O'Neill Desmond , Gibney James , Bourke Nollaig , Reilly Richard , Kennelly Sean 
Published: December 2020

AbstractBackgroundMidlife Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk of dementia in later life. Despite this, few studies have examined the utility of midlife biomarkers to predict later cognitive decline in T2DM. We evaluated the association between dual‐task gait speed and cognitive performance in midlife T2DM as part of ENBIND Study.MethodParticipants with midlife T2DM and matched healthy controls were recruited. Participants with T2DM only included if they had no micro/macrovascular complications of T2DM. Cognition was assessed using the Montreal Cognitive Assessment (MoCA) and computerised neuropsychological assessment battery (CANTAB®). Gait was assessed using both stopwatch and accelerometry across four tasks: (i) self‐selected (usual) gait speed, (ii) maximal gait speed and (iii) dual‐task gait speed (reciting alternate letters of the alphabet). Appropriate univariate statistics in addition to Poisson and linear models were used to analyse results.Results102 cognitively‐intact middle‐aged (52 ± 7.9 years) adults with (N = 71) and without (N = 31) T2DM were recruited. T2DM was associated with a greater likelihood of error on the MoCA (IRR = 2.36, 1.53‐3.64, p<0.001) which persisted after covariate adjustment. T2DM was associated with poorer performance on reaction/movement time, executive function, attention and visuospatial memory tasks, however results were attenuated by covariate adjustment. T2DM was associated with slower gait speed on all three tasks (all p<0.001). Overall, self‐selected, maximal and dual‐task speed were associated with greater likelihood of error on the MoCA (all p<0.001). However, after robust adjustment for covariates, only the association for Dual Task Cost (DTC) persisted (p = 0.021). A DTC*T2DM interaction was not significant.ConclusionsThe current analysis showed diminished cognitive and gait performance in midlife T2DM vs. healthy controls. We observed significant associations between gait performance on the addition of a dual task and general cognitive function. This association, whilst greater in T2DM, was not T2DM specific and adds further evidence for the association between dual task‐gait and cognitive performance in midlife. Our findings support the ongoing exploration and use of gait as a physiological biomarker of overall cognitive function and warrants longitudinal investigation in this high risk group.
Reduction of anticholinergic cognitive burden (ACB) in primary care using a clinical decision‐support software (CDSS) platform
Authors: Zelek Mark C , Walker John Q , Sabbagh Marwan N 
Published: December 2020

AbstractBackgroundMany oral medications can induce a level of “brain fog,” known as Anticholinergic Cognitive Burden. This cognitive burden can be quantified; a consensus on the scoring, from 0 (best) to 3 (worst), has been developed. Drugs with non‐zero scores span pharmacological classes, including antidepressants, antipsychotics, and urological treatments. Higher ACB scores have been correlated with lower performance in cognitive assessments; every 3 points of ACB score may reduce MMSE results by one. This burden confounds cognitive status (i.e., are medications causing observed cognitive impairment?). Recently, some ACB drugs have also been correlated with future dementia incidence.MethodsuMETHOD Health has developed a CDSS platform to address dementia, MCI, and mild AD through the creation of personalized, multidomain treatment plans. The software sums the ACB score across all the medications in someone’s active medication list, showing their impact visually in the generated treatment plan. Drawing from multiple published sources, the platform evaluates 314 generic ACB drugs (including combination drugs). The treatment plans recommend alternatives for each drug with an ACB score of 2 or 3 (called definite anticholinergics). 2,566 individuals aged 65 to 102 comprise the population analyzed here.ResultsIndividuals were an average of 9.5 medications (stdev: 6.5). 75.1% were on anticholinergic medications (mean: 3.4, stdev: 2.7). Had the 350 patients with an ACB score of 5 or more followed the platform recommendations, their average ACB score may have been reduced from 6.94 to 3.3, potentially improving their cognitive assessment performance. Females were taking more anticholinergic drugs than males (2.7 vs. 2.2) and had a higher average ACB score (3.7 vs. 2.7).ConclusionsACB drugs are confounders of cognitive decline, and some are contributors to it. Managing medications is a complex task, the complexity of which increases when dealing with an older population who are not only on more medications, but also have existing comorbidities. The CDSS platform identifies many polypharmacy problems; taking the recommended alternative medications to treat the same comorbidities could lower their ACB score significantly. Clinical professionals should consider ACB analysis part of every visit with their older patients, especially those evincing cognitive decline.
Feasibility and efficacy of the indoor cognitive training combined physical activity (ICT‐PA) program using wearable sensor and mobile device in subjects with mild cognitive impairment
Authors: Han Ji Won , Kim Grace Eun , Moon Woori , Han Ji Hyun , Shin Jeonga , Suh Seung Wan , Shin Jeong Hun , Jeong Won Kyo , Kim Ki Woong 
Published: December 2020

AbstractBackgroundWe developed the Indoor Cognitive Training combined Physical Activity (ICT‐PA) program using wearable sensor for location information. ICT‐PA consists of 1) memory registration of some specific indoor locations using a tablet device, 2) navigating those locations in order and recognition by Bluetooth Low Energy (BLE) tags installed at each of the above words, and 3) recall images placed together at each of the above recognition tags. ICT‐PA aimed to enhance 1) cognitive function by combining verbal/visual memory training and visuospatial navigation training and 2) indoor physical activities by walking during this sequential training. The objective of this study was to evaluate the feasibility and efficacy of ICT‐PA in elderly subjects with mild cognitive impairment (MCI).MethodForty‐three participants aged over 60 years old and diagnosed with MCI participated in the intervention program of 6 weeks. Feasibility was evaluated by checking the satisfaction of the participants with a 5‐point Likert scale. The efficacy of the program on cognitive functions was evaluated by the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery total score (CERAD‐TS) and Mini‐Mental State Examination (MMSE) before and after ICT‐PA. (ClinicalTrials.gov ID: NCT03928613)ResultThirty‐six participants completed both pre‐ and post‐ICT‐PA assessment. The overall satisfaction score was 7.7±1.6 out of 10. The mean CERAD‐TS scores significantly increased after ICT‐PA training (pre, 57.3 ± 11.3; post, 60.3 ± 13.1; p=0.006, paired t‐test), but MMSE did not. Subgroup analysis by compliance (equal to greater than 360 minutes of total use of the ICT‐PA) showed that the compliance group (N=26) improved the CERAD‐TS score (pre, 58.5 ± 11.7; post, 62.7 ± 12.9; p=0.002, paired t‐test), but non‐compliance group did not.ConclusionICT‐PA was effective in improving cognition and was well tolerated by most participants with MCI. Further studies with large numbers of participants and randomized controlled trial are necessary, and the use of at least 60 minutes per week might be suggested. (This work was supported by Institute for Information & communications Technology Promotion (IITP) grant funded by the Korea government (MSIP) (No.2017‐0‐00662, Development of Smart Care system for Dementia Patients based on ICT)).
The burden of dementia and dementia due to Down syndrome, Parkinson’s disease, stroke, TBI, and HIV: An analysis for the Global Burden of Disease study 2019
Authors: Nichols Emma , Vos Theo 
Published: December 2020

AbstractBackgroundIn light of the increasing trends in the global number of individuals affected by dementia and the lack of any available disease‐modifying therapies, it is necessary to fully understand and quantify the global burden of dementia. Previous efforts to quantify the relationships between dementia and stroke, Parkinson’s disease, Down syndrome, traumatic brain injury and HIV, but these analyses have remained isolated and results have not been summarized across disease topics. We estimated the proportion of dementia due to Down syndrome, Parkinson’s disease, clinical stroke, TBI and HIV using consistent and comparable methods, in order to better understand their contribution to the prevalence of dementia.MethodThrough systematic review, we obtained data on the relative risk of dementia with each condition and found sufficient evidence to estimate relative risks for all clinical conditions except HIV. We then estimated relative risks by age using a Bayesian meta‐regression tool and calculated population attributable fractions (PAFs) using the estimates of relative risk and prevalence estimates for each condition from the Global Burden of Disease Study 2019. Finally, we multiplied these estimates by dementia prevalence to calculate the number of dementia cases attributable to each condition.ResultThe relative risk of dementia for all four conditions decreased with age. Relative risks were highest for Down syndrome, followed by Parkinson’s disease, stroke and TBI. However, due to the high prevalence of stroke, the PAF for dementia due to stroke was highest. Overall, Down syndrome, Parkinson’s disease, stroke and TBI explained 9.9% (5.9 to 16.4) of the global prevalence of dementia.ConclusionLess than 10% of dementia prevalence could be explained by Down syndrome, Parkinson’s disease, stroke and TBI. This result emphasizes the large fraction of dementia prevalence unexplained by the four diseases examined in this analysis, and highlights the need for additional epidemiologic research exploring lifestyle risk factors and further research in the basic sciences focused on elucidating intervention approaches to prevent or delay the neuropathological changes that characterize dementia.
Time to invest in nonpharmacological interventions for behaviours and psychological symptoms associated with dementia
Authors: Burley Claire V , Livingston Gill , Knapp Martin Richard John , Wimo Anders , Norman Richard , Brodaty Henry 
Published: December 2020

AbstractBackgroundBehaviours and psychological symptoms associated with dementia (BPSD) affect up to 90% of people living with dementia and strongly correlate with functional and cognitive impairment (Cerejeira et al. 2012). BPSD cause high levels of distress for people living with dementia, families, carer partners and staff, and impose significant service‐related and other costs. Nonpharmacological person‐centred interventions can reduce agitation and other BPSD though uptake is limited. This is possibly due to concerns about cost and staff time, driven by insufficient awareness of studies that have focused specifically on economic analysis and demonstrated potential savings that can be made. We aimed to evaluate the cost‐effectiveness of non‐pharmacological interventions to reduce BPSD.MethodWe reviewed studies that calculated overall cost of BPSD symptoms, costs of individual BPSD (e.g. agitation), and costs of nonpharmacological interventions for reducing BPSD (i.e. cost per unit reduction on the Neuro‐Psychiatric Inventory (NPI) or Cohen‐Mansfield Agitation Inventory (CMAI)). Papers included cross‐sectional, prospective and longitudinal studies, intervention studies and one systematic review.ResultApproximately 30% of total annual cost of a community‐dwelling person living with dementia is invested in the direct management of BPSD (Beeri et al. 2002). Agitation was reported to increase dementia costs by 17% per month in family care costs in a community home care setting (Costa et al. 2018) and 44% in total annual costs in a residential care home setting (Sköldunger et al. 2019). Linear regression approaches show several nonpharmacological interventions were effective in reducing agitation where the incremental cost per unit reduction in CMAI score ranged from £3 to £62 for person‐centred care training, £4 for music therapy, £24 to £143 for sensory interventions and £162 to £3480 for activities (Chenoweth et al. 2008; Livingston et al. 2014). Cost‐effectiveness was also demonstrated for physical activity reducing BPSD (D'Amico et al. 2016).ConclusionPotential savings and cost‐effectiveness gains can be made by investing in treatments for BPSD that are symptom‐targeted and person‐centred, providing strong incentives for service providers to adopt such interventions. Effective partnerships between care providers, researchers and government bodies, and targeted investments are required to support the initiation of these changes.
Global cognitive performance is not influenced by diurnal rhythm
Authors: De Jager Celine H , Burns Eleanna , Stern Yaakov 
Published: December 2020

AbstractBackgroundThere are conflicting reports on the extent to which cognitive performance varies over the course of the day and whether such effects change with advancing age.MethodWe used data collected in two longitudinal studies of cognitive reserve: Cognitive Reserve & Reference Ability Neural Network. We reviewed study documents and extracted the time of the day during which an individual’s cognitive battery. Of 543 subjects with available cross‐sectional data, 281 were tested in the AM and 242 in the PM. Mean age was 55 yo. 178 subjects were <50 yo. Multivariate models were used to evaluate the data.ResultWe found expected effects of age on cognitive performance, but we found no evidence supporting a difference in either global cognitive performance or of performance in one of the four tested domains in relation to time of day. Further, we saw no evidence for an interaction by age: age did not influence performance differences relative to time of day.ConclusionWe have analyzed a large dataset of prospectively collected data in which we see no evidence that time of day influences results of cognitive testing. This analysis settles an important issue that could have implications on study design when subjects select study visits that are convenient for their schedule.
Discovery and development of multi‐target potential of flavonoids as potent acetylcholinesterase inhibitors and anti‐amnestic agents
Authors: Singh Manjinder , Arora Sandeep , Silakari Om 
Published: December 2020

AbstractBackgroundMulti‐target compounds comprise a novel class of therapeutic agents for the treatment of multi‐factorial diseases like Alzheimer’s disease (AD). Following this approach, a new series of flavones were designed, synthesized and biologically evaluated against acetylcholinesterase (AChE), advanced glycation end products formation (AGEs) with additional free radical scavenging activity.MethodOn the basis of proposed hypothesis, 33 flavone derivatives were designed and subsequently synthesized and were primarily evaluated for in vitro AChE inhibitory, AGEs inhibitory and anti‐oxidative activity and prominent compounds further evaluated by in vivo anti‐amnestic activity. After that, molecular docking and Molecular dynamic simulations (MD) were carried out for the most potent compounds to study protein‐ligand interactions.ResultThe in vitro studies showed that the majority of synthesized derivatives inhibited acetylcholinesterase (AChE) with IC50 values in the nanomolar range. Additionally, these compounds also exhibited greater ability to inhibit advanced glycation end products formation in micromolar range with additional radical scavenging property in nanomolar range. The most active compounds were also ameliorated scopolamine‐induced amnesia in mice in terms of restoration of time spent in target quadrant (TSTQ) and escape latency time (ELT). Moreover, the molecular docking study displayed that most potent compounds simultaneously bind to catalytic active site (CAS) and peripheral anionic site (PAS) of AChE.ConclusionIn conclusions, the results support the proposed hypothesis that newly designed multi‐target flavones have the ability to act on different targets or exhibit multiple pharmacological activities related to Alzheimer’s disease. Thus, flavones might be the promising lead compound as potential multi‐target anti‐Alzheimer’s agents.