bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aetiology and prognosis of the motoric cognitive risk syndrome: A population‐based comparison with mild cognitive impairment
Authors: Yaqub Amber , Darweesh Sirwan K.L. , Dommershuijsen Lisanne J. , Wolters Frank J. , Ikram M. Arfan 
Published: December 2021

AbstractBackgroundThe motoric cognitive risk syndrome (MCRS) has been proposed as a dementia prodrome that improves clinical risk stratification, by integrating slow gait and cognitive complaints. It remains undetermined to what extent pathophysiological substrates in terms of clinical risk factors, neuroimaging correlates and associations of MCRS with dementia are independent of the widely used concept of mild cognitive impairment (MCI).MethodsBetween 2009 and 2015, subjective cognitive complaints, objective cognitive impairment and gait speed were assessed in 3,025 dementia‐free participants of the population‐based Rotterdam Study (mean age 70.4 years, 54.7% women). In line with prior studies, MCI and MCRS were defined as subjective complaints along with a score of >1.5 and >1 standard deviations below the population mean of the neuropsychological test battery and gait speed, respectively. We used multinomial logistic regression models to determine cross‐sectional associations of clinical risk factors and neuroimaging markers with MCI and MCRS, and subsequently assessed risk of dementia or death, with follow‐up until 2016, in a competing risk framework.ResultsOf 3,025 individuals, 231 had MCRS (7.6%), 132 had MCI (4.4%), and 62 (2.0%) fulfilled criteria for both. Smoking, hypertension, diabetes and APOE‐ε4 carriership were shared risk factors between MCRS and MCI, but higher BMI predisposed predominantly to MCRS, whereas male sex and hypercholesterolemia were associated with MCI only. Lower total brain volume was more strongly related to MCI than to MCRS, driven by a difference in white matter volume. During a mean follow‐up of 3.9 years, 71 individuals developed dementia and 200 died. Compared to unaffected individuals, risk of dementia was higher with MCI and to a lesser extent with MRCS (subdistribution hazard ratio [95% confidence interval]: 6.95 [3.78‐12.75] and 3.55 [1.91‐6.60], respectively). Accounting for a higher mortality risk, 5‐year risk of dementia was 7.0% [2.5‐11.5%] for individuals with MCRS, versus 13.3% [5.8‐20.8%] with MCI and 2.3% [1.5‐3.1%] in unaffected individuals.ConclusionIn people with subjective cognitive complaints, both cognitive and motor function impairment are associated with dementia risk, with in part different pathophysiological substrates. While MCI has greater utility for dementia prediction, incorporation of motor function in clinical assessments may increase prognostic accuracy.
Healthy lifestyle and cognitive decline in people living with stroke in the community
Authors: Dhana Klodian , Aggarwal Neelum T , Beck Todd , Desai Pankaja , Liu Xiaoran , Barnes Lisa L , Evans Denis A , Rajan Kumar B 
Published: December 2021

AbstractBackgroundA healthy lifestyle is associated with a slower cognitive decline and reduced risk of Alzheimer’s dementia in the general population. Whether such a healthy lifestyle exerts cognitive benefits among people living with stroke in the community deserves examination.MethodThe analyses used 5,324 older individuals without dementia participating in the Chicago Health and Aging Project, a population‐based cohort study. Of 5,324 participants, 1,030 individuals had a stroke at the baseline or developed it over study period. We followed up 1,030 participants with stroke and 1,030 stroke‐free individuals matched by age, sex, race, and examination cycle, for changes in cognitive functioning. The primary exposure was healthy lifestyle score that included five factors, non‐smoking, moderate exercise, being cognitively active, having a high‐quality diet, and limiting alcohol use – giving an overall score ranging from 0 to 5. Global cognitive function was evaluated every 3‐years using a short‐battery tests consisting of two tests of episodic memory, one test of executive function, and the MMSE. Multivariable adjusted linear mixed effect models were used to estimate the role of a healthy lifestyle score on cognitive decline.ResultThe average age of participants with stroke was 76 years, 62% were women, and 64% were African Americans. These characteristics were similar to the overall study population (n=5,324). Compared to people without stroke, participants with stroke had 22.3% (beta ‐0.019 unit/year; 95%CI ‐0.03, ‐0.008) faster cognitive decline during follow‐up. The healthy lifestyle score was associated with a slower cognitive decline in participants with and without stroke. Each unit increase in healthy lifestyle was associated with 8.7% (beta 0.010 unit/year; 95% 0.001, 0.018) slower annual cognitive decline in people with stroke and 7.3% in people without stroke. The annual cognitive decline rate in individuals with 4‐5 healthy lifestyle factors compared with those with 0‐1 factor was 32.7% (beta 0.033 unit/year; 95%CI 0.002, 0.064) slower in participants with stroke and 34.0% (beta 0.030 unit/year; 95%CI 0.006, 0.053) slower in participants without stroke.ConclusionIn community‐dwelling stroke survivors, a higher healthy lifestyle score was associated with better cognitive functioning, suggesting that these lifestyle factors may exert cognitive benefits after stroke.
The influence of cognitive ability on older adults’ ability to take over driving control from an automated vehicle
Authors: Haghzare Shabnam , Campos Jennifer L. , Delfi Ghazaleh , Stasiulis Elaine , Rapoport Mark , Naglie Gary , Mihailidis Alex 
Published: December 2021

AbstractBackgroundAutomated vehicles (AVs) hold potential promise in sustaining the safe mobility of older adults whose driving is compromised due to cognitive impairments. However, current AVs have an operational limit and when this limit is reached, the driver is expected to promptly take over driving control. The timely performance of takeover task draws upon cognitive resources that can be compromised in people with dementia (PwD) and people with Mild Cognitive Impairments (PwMCI). Therefore, this study investigates the abilities of PwD and PwMCI to perform an AV driving takeover task.Method
Population. 20 participants per three groups of PwD, PwMCI, and older adult controls will be recruited. Currently, the data collection for the controls and recruitment for the PwD and PwMCI are on‐going. The present results are based on seven control participants who have completed the study to date. Study Design & Setting. Participants completed a battery of sensory and cognitive tests and performed takeover tasks in response to an audio‐visual alert in a simulated AV using a high‐fidelity driving simulator. Each participant performed takeovers in eight driving conditions varying in lighting level (day/night), road structure (straight/curved), and speed limit (60/120 km/h). Measures. To characterize participants’ takeover abilities, their response time was measured as the time interval between the audio‐visual alert and uptakes in speed (longitudinal takeover time), and changes in steering wheel angle (lateral takeover time).ResultA correlation analysis was conducted between each of takeover time measures and cognitive and visual tests. MoCA scores showed a significant, negative correlation with lateral takeover time (r
k = ‐0.85, p = .015, 95% CI [‐0.98, ‐0.27]). To investigate the effects of driving condition on takeover time, pairwise Kruskal‐Wallis tests were conducted on measures of takeover time as separated by driving condition. Significant differences were only observed in lateral takeover time in the curved, high‐speed condition compared to other conditions (χ2(3) = 29.46, p < .001).ConclusionThis study will help clarify the associations between older adults’ cognitive abilities and takeover abilities in AVs which can, in turn, inform the guidelines around the safe use of AVs by PwD and PwMCI.
Predictive factors for conversion to dementia in individuals with early‐onset mild cognitive impairment
Authors: Baird Kate , Baillon Sarah , Lau Lilian , Storey Mathew , Lindesay James , Velayudhan Latha 
Published: December 2021

AbstractBackgroundEarly‐onset Mild Cognitive Impairment (eoMCI) is defined as difficulties in cognition that are worse than in normal ageing for individuals below the age of 65. Some will go on to develop dementia, but there is currently limited research on which risk factors make someone more vulnerable to conversion. The present study aimed to examine whether sociodemographic and clinical factors at the initial presentation predict dementia progression in a cohort of eoMCI patients attending a memory service, at a university teaching hospital in the United Kingdom.MethodsA retrospective case note study utilising a database of individuals diagnosed with eoMCI between 2000‐2010 at a Younger Person’s Memory Service (YPMS) in Leicestershire, England. Data collected at assessment included social factors, demographic characteristics, medical and psychiatric history, as well as standardised cognitive assessment scores.ResultsOut of 531 subjects who attended YPMS between Jan 2000 to Dec 2010, 65 patients were diagnosed with eoMCI (47.7% female; age 56.4 years ±7.54). Of these, 21 individuals (32.3.%) converted to dementia during their course within the service. The mean period of conversion was 30.40 months (±23.08). A comparison between the subgroups revealed a significant association between dementia conversion and higher years of education, lower MMSE and CAMCOG (total and subscores) scores. A subsequent survival analysis found that higher education, lower CAMCOG score, impaired memory (remote, recent, learning) and impaired executive functions, at initial assessment were significant predictors for converting to dementia.ConclusionHigher education, impaired memory and impaired executive functions at initial assessment are associated with a progression to a dementia diagnosis. The present naturalistic study identifies potential characteristics that predict the likelihood of an individual with eoMCI converting to any type of dementia. This has vital clinical implications and additional research is needed to explore these risk factors further.
Acute cerebral blood flow response to lipid ingestion in older adults: A pilot study
Authors: Ashford Nathaniel K. , Rane Swati , Gandhi Tarun , Farris Kristen , Hanson Angela J. 
Published: December 2021

AbstractBackgroundHigh fat feeding (HFF) is a risk factor for Alzheimer’s disease (AD), and acute meal studies including lipid tolerance tests can be used to understand mechanisms by which diet affects disease processes. This study seeks to describe cerebral blood flow (CBF) response using arterial spin labeling (ASL) MRI, given the tight coupling of CBF to brain metabolism.MethodAfter fasting, 16 older adults (age 66.3±2.9) underwent baseline and 1, 2, 3‐hour ASL MRI after ingestion of 1/2 cup heavy cream with comparable total and saturated fat to a high fat breakfast. We used pCASL MRI with background suppression to measure CBF in ml/100g/min. Imaging parameters were in accordance with the recommendations of ISMRM: label duration = 1.8 s, post‐labeling delay = 2 s, labeling offset = 25‐30 mm, slices = 20, resolution = 3.5×3.5×5 mm3, SENSE‐factor = 2, TR/TE= 5000/18 ms. Finally, we acquired a reference scan (M0, 1 minute) identical to the above scan but with TR = 10,000 ms and no labeling or background suppression. Statistical analyses included paired t tests and ANOVA for group comparisons.ResultGlobal CBF decreased at 1, 2, and 3 hours post‐lipid drink, compared to time 0 (1h:‐2.12±4.1, 2h:‐1.9±3.2, 3h:‐2.9±3.1); only 2 and 3 hours were statistically lower. No group differences by sex or APOE status were noted in baseline or change CBF for this small pilot sample.ConclusionGlobal CBF decreased after lipid ingestion, similar to what has been reported with glucose and fructose ingestion. Sustained decreases in CBF were still detectable at 3 hours. Future studies include investigation of pre‐post CBF in various regions known to be affected by AD.
Spatiotemporal trends in dementia‐associated deaths, what do the data reveal?
Authors: Parkinson Luisa , Lindgren Finn , Russ Tom C 
Published: December 2021

AbstractBackgroundData on dementia mortality are routinely collected by governments and used in health research. However, historical underrecording of dementia on death certificates has limited the utility of this widely available data source. Considerable effort has been invested in raising awareness of dementia, increasing diagnosis rates, and improving dementia recording on death certificates. Updated versions of the ICD‐10 rules for coding the underlying cause of death, implemented in Scotland in 2011 and 2017, have increasingly assigned deaths that mention both dementia and respiratory or urinary tract infections towards an underlying cause of dementia, if no other underlying medical condition is mentioned. Since previous cohort studies have shown geographical variation in dementia risk, this study utilises spatiotemporal modelling to investigate changes in dementia‐associated deaths in Scotland.MethodData on dementia and Alzheimer’s deaths and mid‐year population estimates available from the National Records of Scotland for the time period 2000‐2019 were used to build a Bayesian spatiotemporal disease mapping model. The data were grouped by the 32 Council areas and year, whilst stratification by age and gender were built into the model. The analyses were run in R using Integrated Nested Laplace Approximation methodology.ResultThe data show strong temporal and spatial trends in the relative risk of dementia‐associated death. The relative risk increases progressively over the time period studied, with a 2.3‐fold increase (95% Confidence Interval: 2.1‐2.5) between 2000 and 2019, reaching levels just below predicted dementia prevalence in recent years. The relative risk varies geographically and is highest in Scotland’s industrialised central belt region and lowest in the rural areas and islands, with a relative risk of 1.9 (95% CI: 1.6‐2.3) between the lowest and highest risk Council areas.ConclusionThere are factors, other than the step changes in underlying cause of death coding, driving the progressively increasing temporal trend in relative risk of dementia‐associated death. These factors could be a combination of increased dementia awareness, a larger proportion of people being diagnosed, greater recording on death certificates and, possibly, increasing prevalence. The strong spatial variation in relative risk in Scotland indicates that there are geographically‐varying factors affecting this risk.
Apathy across neurodegenerative disorders is associated with sex‐specific changes in sub‐cortical and cortical grey matter volumes
Authors: Tumati Shankar , Lanctôt Krista L. , Seitz Dallas , Herrmann Nathan 
Published: December 2021

AbstractBackgroundApathy is frequent in all neurodegenerative disorders (ND) but it is not known whether apathy across these diagnostic groups is associated with common brain changes. Here, we investigated if MRI‐derived grey matter volumes (GMV) predicted apathy across these disorders.MethodSubjects from the Canadian Consortium on Neurodegeneration in Aging’s COMPASS‐ND cohort were diagnosed with clinical and MRI assessments. Apathy was defined on the Neuropsychiatric Inventory questionnaire. GMV derived from cortical and sub‐cortical regions were used to predict apathy in subjects with ND, controlling for age, sex, years of education (YoE), and total GMV.ResultIncluded subjects (n=386, 72.5 ± 7.3y, 43.5% F, YoE: 15.6 ± 3.8y, Montreal Cognitive Assessment score (MoCA): 23 ± 4.4) were diagnosed with subjective cognitive impairment (n=55), mild cognitive impairment (MCI, n=144), Alzheimer’s disease (n=56), Parkinson’s disease (PD) without cognitive impairment (n=34), PD‐MCI (n=23), PD dementia (n=6), vascular MCI (n=15), mixed dementia (n=25), Lewy body dementia (n=14), and Frontotemporal dementia (n=12).Apathy was present in 114 (29.5%, 72.9 ± 7.2y, 23.7% F, YoE: 15.3 ± 4.1y, MoCA: 21.1 ± 4.2) subjects. After adjusting for covariates, apathy was predicted by lower left (B=‐2.37, z=‐2.84, pfdr=.044) and higher right GMV (B=2.34, z=2.92, pfdr=.044) of the caudate nucleus. Apathy was better predicted by men (B=1.36, z=3.89, pfdr=.003); hence the analysis was repeated separately in men and women. In men (n=218, apathy=87), in addition to caudate GMV (left: B=‐2.79, z=‐2.73, pfdr=.044; right: B=2.85, z=2.83, pfdr=.044), apathy was predicted by higher left (B=2.74, z=2.84, pfdr =.044) and lower right (B=‐3.42, z=‐3.32, pfdr=.025) GMV in the putamen; in women (n=168, apathy= 27), apathy was predicted by higher left (B=22.4, z=3.5, pfdr =.006) and lower right (B=‐21.85, z= ‐3.64, pfdr =.006) frontal lobe GMV but not caudate GMV.ConclusionIn a large cohort of ND patients, GMV changes in caudate nuclei were associated with apathy. Importantly, apathy in women was associated with frontal lobe GMV changes, suggesting that the neural correlates of apathy might differ in men and women.
Co‐designing toolkits to improve post‐diagnostic support for people living with dementia, care partners and health and social care professionals (COGNISANCE)
Authors: Wilcock Jane , Poole Marie , Brodaty Henry , Robinson Louise , Rait Greta ,   Cognisance Research Team
Published: December 2021

AbstractBackgroundCOGNISANCE is an international research programme (Australia, UK, Canada, Netherlands, and Poland). In partnership with people living with dementia, informal care partners, health and social care professionals and key national and international dementia organisations and researchers, we have co‐designed online toolkits aiming to improve post‐diagnostic support for dementia.MethodsWe have worked closely with local working groups representing members from key audiences and a design and marketing agency to run a series of workshops in five countries. The workshops to date have focussed on the key messages, motivators for information seeking, experiences of dementia diagnosis and post diagnostic support, the purpose for toolkits and the tone and branding appropriate for the key audiences for a resource that focusses on the first twelve months post‐diagnosis.ResultsCo‐design workshops were successfully run concurrently in five partner countries. Each country’s research team and local working groups remained highly engaged throughout the process. Key motivators for the toolkits led to a focus on a practical and empathetic resource that was tailored to the individual. The toolkits will be a website that has three separate pathways, one for people recently diagnosed with dementia, one for care partners and one for health and social care professionals. These will function to support communicating the diagnosis, post‐diagnostic support and planning for the first year post diagnosis. The design and marketing agency have worked closely with research teams and local working groups throughout the co‐design process to interpret and build iteratively on each workshop outcome. From this we have successfully produced a generic website that can be tailored in different locations to the three key audiences.ConclusionIn the co‐design process, representative users identified the need for a practical, empathetic and individually‐tailored resource. The toolkit will be a website that has an individual planning tool for the first twelve months following a dementia diagnosis. We are continuing the co‐design process to develop a campaign. This will promote the key messages and toolkit, to plan for a life with dementia, ahead of user testing, implementation and evaluation.
Differences in white matter integrity and hippocampal volumetrics across APOE genotype mice: A blinded preliminary study
Authors: Bhattrai Avnish , Raikes Adam C. , Mishra Aarti , Brinton Roberta Diaz 
Published: December 2021

AbstractBackgroundGenome‐wide association studies have identified Apolipoprotein (APOE) as one of the strongest risk factors associated with Late‐Onset Alzheimer’s disease (LOAD) with females exhibiting a two‐fold higher incidence as compared to males. MRI studies of patients with LOAD link APOE‐e4 gene load with increased hippocampal volume loss as well as reduction in white matter integrity (WMI) in the limbic and medial temporal regions (Bagepally, 2012). However, there are few translational LOAD mouse model studies utilizing imaging. We hypothesized that hippocampal volume and WMI would be reduced in females and APOE e4 carriers in our humanized APOE (hAPOE) LOAD mouse model.MethodSix cohorts of APOE e3 and e4 genotype (M/F; N=53; mean age = 17.95 month) skull‐extracted ex‐vivo mouse brains were imaged (7T Bruker Biospec MRI scanner). Imaging included structural and diffusion weighted imaging. Bilateral hippocampal volumes, as well as total brain volume (TBV), were extracted using a well‐validated mouse brain atlas (Dorr, 2008). Fractional anisotropy (FA) was used to quantify WMI and between‐group comparisons were made using a groupwise connectometry approach (Yeh, 2013; Yeh, 2016).ResultMRI image analysis indicated genotypic differences in white matter FA where APOE‐e4 carriers exhibited lower FA values (mean tractography FA = 0.263 ± 0.043) compared to APOE‐e3/3 (mean tractography FA = 0.311 ± 0.067) in a total of 10657 tracts (FDR corrected p < 0.003; Figure 1). No statistically significant differences were identified across genotypes for left or right hippocampal volumes. However, right hippocampal volume was significantly greater in males as compared to females (p = 0.007) whereas no effect was observed between sexes for left hippocampus.ConclusionOutcomes of MRI analyses indicate a significant reduction in FA values and reduced white matter integrity across the brain in APOE e4 carriers, irrespective of sex. Contrary to human literature, no significant volumetric differences between genotypes were found in this mouse sample. Consistent with sex‐dependent literature, males exhibited greater total brain volume and additionally greater right hippocampal volume compared to females, irrespective of genotype. These findings may provide evidence of deficits in cholesterol or lipid transport manifest in decreased white matter integrity in this hAPOE mouse model.