bluuebunny/crossref_metadata_2025_split huggingface dataset:
Objective subtle cognitive decline is associated with a more rapid increase in plasma phosphorylated‐tau181 levels over time
Authors: Thomas Kelsey R. , Bangen Katherine J. , Edmonds Emily C. , Weigand Alexandra J. , Walker Kayla S. , Bondi Mark W. , Galasko Doug R. 
Published: December 2021

AbstractBackgroundEarly identification of Alzheimer’s disease (AD) is imperative for early intervention and planning. Objectively‐defined subtle cognitive decline (Obj‐SCD) criteria, based on sensitive neuropsychological scores, is associated with AD biofluid and neuroimaging markers as well as progression to mild cognitive impairment (MCI) and dementia. However, the relationship between Obj‐SCD and newer plasma markers, such as plasma phosphorylated‐tau181 (p‐tau181), is unknown. Therefore, we examined baseline and longitudinal plasma p‐tau181 across CN, Obj‐SCD, and MCI groups.Method953 Alzheimer’s Disease Neuroimaging Initiative participants without dementia had plasma p‐tau181 data, which were log‐transformed prior to analyses. Participants were classified as CN (n=403), Obj‐SCD (n=200), or MCI (n=350) based on actuarial neuropsychological criteria. Baseline analyses compared p‐tau181 across groups. Linear mixed effects models, adjusting for age, sex, APOE e4 allele frequency, and pulse pressure, examined 4‐year p‐tau181 rate of change in Obj‐SCD and MCI participants relative to CN. Follow‐up analyses examined whether the group p‐tau181 x time trajectories differed by Aβ‐PET positivity status.ResultCN and Obj‐SCD groups had lower baseline plasma p‐tau181 than the MCI group and did not differ from one another (Figure 1). However, longitudinally, the Obj‐SCD group had the steepest increase in plasma p‐tau181 over four years and was the only group to differ from CN participants (Figure 2; b=.016, 95% CI: .003‐.018, p=.016). When groups were split by Aβ status, only the Aβ‐negative Obj‐SCD group showed a slightly faster increase in p‐tau181 relative to the Aβ‐negative CN group (b=.019, 95% CI: .001‐.037, p=.044).ConclusionBaseline plasma p‐tau181 did not differ between CN and Obj‐SCD; however, consistent with prior findings, Obj‐SCD was associated with future pathologic changes, including those measured by plasma p‐tau181, prior to frank impairment associated with MCI. Importantly, these results do not appear to be driven by Aβ+ Obj‐SCD participants. Despite the long‐held assumption that cognitive changes invariably follow biomarker changes, these findings suggest that early neuropsychological difficulties may emerge before or in tandem with measurable changes in plasma markers. Future work will examine the prognostic impact of combining Obj‐SCD and plasma markers, which both have the potential to be accessible early markers of future AD‐related declines.
Early detection of neuropsychiatric, language and motor symptoms in genetic frontotemporal dementia (FTD): Defining prodromal FTD
Authors: Samra Kiran , Russell Lucy L , Greaves Caroline V , Convery Rhian S , Rohrer Jonathan D ,   Genetic Frontotemporal Dementia Initiative (GENFI)
Published: December 2021

AbstractBackgroundThe prodromal stage of genetic frontotemporal dementia (FTD) is currently poorly defined. Whilst the majority of people with genetic FTD develop behavioural symptoms, a number of people present with primary progressive aphasia (PPA), neuropsychiatric symptoms, parkinsonism, including corticobasal syndrome (CBS) or progressive supranuclear palsy (PSP), or amyotrophic lateral sclerosis (ALS). Such variable phenotypes pose a barrier to clearer definitions of prodromal FTD.Methods1139 people have been recruited to the Genetic FTD Initiative (GENFI), a deep phenotyping international multicentre cohort study of FTD. Clinical data on symptoms within the language, neuropsychiatric and motor domains have been collected on presymptomatic and symptomatic mutation carriers, as well as mutation‐negative controls using the GENFI Symptom Scales.Results
Language: In the symptomatic phase, 19 participants met Gorno‐Tempini diagnostic criteria for primary progressive aphasia (PPA), the majority (17) of whom had a progranulin (GRN) mutation. The phenotype in these cases was either nonfluent variant (8) or did not meet criteria for a specific variant (9). Additionally, 42 presymptomatic participants had subtle early language problems. Neuropsychiatric: Symptoms were reported most frequently in symptomatic C9orf72 mutation carriers (91.7% of all symptomatic C9orf72 carriers) and to a lesser extent in GRN and MAPT mutation carriers. Depression and anxiety were common in mutation‐negative controls (14%) as well as mutation carriers. Motor: ALS and FTD‐ALS were most frequent in C9orf72‐associated FTD (12.5% of all symptomatic C9orf72 carriers). Parkinsonism (including PSP and CBS) was present to a lesser extent in C9orf72, GRN, and MAPT mutation carriers.ConclusionsLanguage, neuropsychiatric and motor features are common in genetic FTD and will need to be included in any prodromal staging system. Improved, operationalised measurement of such symptoms will allow improved stratification of individuals, and aid clinical trials. Future work should unravel the temporal trajectory of such symptoms within each form of genetic FTD.
Assessing cognition in the era of COVID19: Do we need methods to assess cognitive function virtually?
Authors: Saxena Saket , Factora Ronan , Hashmi Ardeshir , Jones Robert , Baranek Laura , Sefcik Mary , Alexio Gabriel 
Published: December 2021

AbstractBackgroundWith an aging population, cognitive impairment has become increasingly prevalent. Early symptoms are often missed in primary care and may progress to clinical dementia before being noticed. Screening for dementia has been a challenge. No clear guideline describes how to assess for cognition in primary care despite the robust data suggesting that early identification of dementia allows for mobilization of resources to support patients and caregivers, and there is no harm in proactive assessing cognition in older patients. In addition, most of the cognitive assessment methods requires in‐person cognitive testing in primary care practices, this may be affected by situations where the in‐person visitations to the physician offices are limited such as in the COVID 19 pandemic. Our study aims to access performance of in‐person cognitive assessment in primary care during COVID 19 pandemic.MethodsCleveland Clinic implanted MiniCog as a cognitive screening tool in primary care at Cleveland Clinic Community Care (4C). Inclusion criteria are‐ Age 65+, Annual Wellness visit, no preexisting diagnosis of dementia, normal MiniCog in previous year. Data were registered from from January 2019 until November 2020.ResultsFigure 1 displays the number of MiniCog performed at 4C averaging 360 MiniCog every month. Total number of MiniCogs performed during the study period was 7126 out of which 6739 were normal (95%) and 387 were abnormal (5%). Figure 2 displays the impact of COVID 19 pandemic on in‐person visits in 4C, resulting an impressive decline in cognitive assessment process leading to no cognitive testing in April and only two tests in May.ConclusionMost of the cognitive assessment tools used in clinical practice requires in‐person office based and are often needed to diagnose dementia. Telephonic cognitive interviews such as TICS and MoCA 5 minute protocol are available, but are difficult to administer in primary care. The substantial drop in the performance of in‐person cognitive assessment during the COVID 19 pandemic raises the need of validated tools to virtually assess cognitive function and also highlights the negative impact of COVID 19 pandemic on already frail processes of assessing cognitive health of older adults in primary care.
Evaluating predictability in outdoor mobility: A potential pathway to personalized assistance for people with dementia
Authors: Bayat Sayeh , Naglie Gary , Rapoport Mark , Stasiulis Elaine , Ye Bing , Mihailidis Alex 
Published: December 2021

AbstractBackgroundPeople with dementia (PwD) often become lost, which is commonly attributed to spatial disorientation, one of the earliest symptoms of dementia, particularly of the Alzheimer’s disease type. Spatial disorientation can limit a person's ability to navigate in an outdoor environment. As a result, PwD experience outdoor mobility decline, which, in turn, can have a negative impact on their cognitive functions. Thus, enabling safe outdoor mobility is important for dementia research. Artificial Intelligence (AI) methods in conjunction with Global Positioning System (GPS) data show great potential for supporting the outdoor mobility needs of PwD. The objective of this work is to evaluate the extent to which we can predict future destinations of PwD by learning from their past mobility habits.MethodEight cognitively‐intact older adults (CTL) and seven older adults with dementia completed four weeks of GPS recording. Each participant’s stops and trips were extracted from their trajectories. We determined the predictability of each participant’s mobility patterns using three approaches. First, we assumed each stop is visited with equal probability, thus, disregarding temporal aspects of travel. Next, we built on the previous approach by including stop visitation probability, thus, capturing the heterogeneity of visitations. Finally, to capture the full spatiotemporal characteristics of mobility, we added in‐depth temporal characteristics including the visitation frequency, the order in which the stops were visited, and the time spent at each stop.ResultRelying solely on the spatial dimension of mobility yielded no predictive power across the two groups. Adding the heterogeneity of visitation patterns, we observed an increase in the predictability power; PwD displayed a trend toward higher predictability compared to the CTLs, but the student’s t‐test did not reach statistical significance (0.833±0.085vs.0.768±0.029, t(13)=‐2.06, p=0.06; d=‐1.07). Finally, relying on full spatiotemporal characteristics, a 4‐week record of mobility patterns displayed 95% (SD=2%) and 92% (SD=1%) predictability among PwD and CTLs, respectively. This value was significantly higher among PwD, t(13) = ‐3.39, p<.01; d=‐1.75.ConclusionOur findings offer new perspectives on the predictive mobility models based on GPS data and AI that can be used to provide personalized assistance for outdoor navigation of people with dementia.
Lessons from SPRINT‐MIND on interventions to prevent dementia
Authors: Williamson Jeff D. 
Published: December 2021

AbstractBackgroundThe Systolic Blood Pressure Intervention Trial (SPRINT) and the Systolic Blood Pressure Intervention Trial: Memory and cognition IN Decreased hypertension (SPRINT‐MIND) have contributed substantially to recent advances in the fields of hypertension, cardiovascular disease prevention, and prevention of cognitive decline.MethodRandomized clinical trial of 9,361 adults (mean age, 67.9 years) with hypertension and increased risk for cardiovascular disease with a mean follow‐up of 5.5 years. Participants were from diverse communities in the United States and were 27.8% black and 10.5% Hispanic.ResultSPRINT‐MIND has already demonstrated in this randomized trial that intensive blood pressure control significantly reduces the risk of incident overall mild cognitive impairment (HR, 0.81; 95% CI, 0.69‐0.95). However results related to subtype of MCI have not been released. This presentation will expand on findings related to intensive blood pressure control and the incidence of mild cognitive impairment (MCI) and Probable Dementia. The beneficial effect on MCI largely reflected in amnestic subtypes (HR, 0.78 [95% CI, 0.66‐0.92]) and multi‐domain MCI subtypes (HR, 0.78 [95% CI, 0.65‐0.93]), with no significant differences for non‐amnestic and single domain MCI subtypes. Data on the the mean scores each component of the cognitive battery according to adjudicated participant classification of 1) No impairment, 2) MCI or 3)Probable dementia will also be presented.ConclusionFindings from the SPRINT‐MIND trial continue to enhance understanding of the importance of cardiovascular disease prevention approaches as a pathway for also reducing the burden of cognitive impairment and dementia.
Can we re‐purpose drugs from the cardiology medicine cabinet? Should we look in the rheumatology, metabolic and hematology cabinets as well?
Authors: Quinn Terence J ,   Dementias Platform UK Vascular Experimental Medicine Group
Published: December 2021

AbstractBackgroundDespite substantial investment, the dementia drug development pipeline has failed to produce a convincing new pharmacological treatment. This situation is in stark contrast to drug development in oncology, metabolic and cardiovascular medicine, where many novel agents are entering phase III trials or clinical practice. Some of the commonly prescribed medications for brain disorders were originally developed for another therapeutic indication (memantine and tPA are examples). In this session we will consider whether re‐purposing existing or novel drugs from other disease areas could offer a treatment for dementia?MethodThe ultimate test of a new medication is the randomised controlled trial. Contemporary trials are costly. For drug repurposing we can exploit available data from trials and registries to inform the choice of candidate drugs and ‘de‐risk’ the development process. There are various approaches, and we will consider: expert consensus; systematic review and meta‐analysis; individual participant level evidence synthesis; genome wide association studies; drug wide association studies. Secondary analysis of existing trial and healthcare data can also inform the design, sample size and conduct of a repurposing study. As part of the Dementias Platform UK (DPUK) portfolio, we are utilising all these methods with the anticipation of selecting the most promising candidates to take forward to clinical trials.ResultThere are already good examples where existing data have informed or are informing drug repurposing studies. These include non‐steroidal and other anti‐inflammatory drugs (e.g. cilostazol); antithrombotic agents (e.g. dabigatran); antihypertensive or vasodilator medications (e.g. losartan, tadalafil); novel drugs developed for heart failure and diabetes mellitus (e.g. GLP1 agonists, such as liraglutide). Emerging data are already suggesting plausible candidates, while also giving new insights into the pathogenesis that underlies cognitive decline. We will share progress made within the DPUK Vascular group and offer a roadmap for future repurposing research.ConclusionThe search for an effective dementia intervention continues. It is possible that we already have useful medications that we can ‘borrow’ from other clinical fields. The increasing number of medications coupled with access to large volume, robust data‐sets creates an ideal landscape for selecting candidate drugs for repurposing.
The association between diabetes and Alzheimer’s disease pathophysiology
Authors: van Gils Veerle , Vos Stephanie JB , Jansen Willemijn J , Martinez‐Lage Pablo , Hort Jakub , Ramakers Inez HGB , Soininen Hilkka , Laakso Markku , Zetterberg Henrik , Dalsgaard Søren , Verhey Frans RJ , Visser Pieter Jelle ,   EMIF‐AD MBD Consortium
Published: December 2021

AbstractBackgroundDiabetes is common in persons with dementia and associated with cognitive decline. However, the relation between diabetes and AD pathophysiology is still unclear. Our aim is to assess the association of diabetes diagnosis and blood glucose regulation with CSF AD biomarkers across the AD clinical spectrum, and the potential moderating effects of vascular factors in this relationship.MethodAs part of the PRIME project, we included individuals from five European memory clinic cohorts with normal cognition (NC, n=419) mild cognitive impairment (MCI, n=363) and dementia (n=151). Inclusion criteria were availability of diabetes diagnosis, fasting blood glucose or HbA1c levels and cerebrospinal fluid (CSF) biomarkers amyloid‐beta42, p‐tau and t‐tau. Center‐specific cut‐offs were used to define biomarker positivity. We performed logistic and linear regression models adjusted for age, education years, gender, cohort, to assess the relation between diabetes and AD biomarkers, as well as the potential influence of hypertension, hypercholesterolemia and BMI on this relationship.ResultWe included 933 participants in our analysis with an average age of 66.1 years (Table 1). Diabetes was associated with lower odds of being amyloid positive in the total group and in individuals with NC and dementia (Table 2). Diabetes was associated with a lower risk for p‐tau and t‐tau positivity in the total group and in the MCI subgroup. Similar trends were found with HbA1c and blood glucose as predictors. A higher BMI was associated with less t‐tau pathology in persons with diabetes only. Presence of hypertension and hypercholesterolemia did not influence the association between diabetes and AD biomarkers. Additionally, post‐hoc analyses with diagnostic group stratified for amyloid positivity were performed. These analyses indicated that amyloid‐negative demented individuals more often had diabetes than amyloid‐negative NC and MCI individuals (Figure 1). Relative to amyloid‐negative NC, amyloid‐negative demented individuals had higher HbA1c and glucose levels (Figure 2). Amyloid‐positive demented individuals had higher HbA1c levels than amyloid‐positive NC and MCI patients.ConclusionDiabetes and impaired glucose regulation are associated with non‐AD dementia but not with AD‐related cognitive impairments. Surprisingly, amyloid positive individuals with normal cognition less often had diabetes.
CSF apolipoprotein B levels predict future visuospatial cognitive decline and synaptic pathology in cognitively unimpaired healthy elderly with a parental history of Alzheimer’s disease
Authors: Poirier Judes , Nilsson Nathalie I.V. , Labonté Anne , Rosa‐Neto Pedro , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Breitner John , Villeneuve Sylvia , Picard Cynthia , Group Prevent‐AD Research 
Published: December 2021

AbstractBackgroundWe examine the role of brain apolipoprotein B (apoB) as a putative CSF indicator of early tau pathology in pre‐symptomatic Alzheimer’s disease (AD).MethodAmong 129 cognitively unimpaired elderly at increased risk of AD (PREVENT‐AD cohort), we assessed blood and cerebrospinal fluid apoB, apoC3 and apoE protein levels with those of amyloid β42, total tau and phosphorylated tau. We compared results with amyloid‐b (NAV4694) and tau (flortaucipir) positron emission tomography uptake and cognitive assessment alterations over 6‐8 years. Tangle and plaque pathologies were contrasted with cortical APOB, APOC3 and APOE mRNA levels in 240 autopsied subjects enrolled in the Religious Orders Study and Memory and Aging Project (ROSMAP) studies with diagnoses of cognitively unimpaired, mild cognitive impairment, or AD.ResultAmong cognitively unimpaired participants, we observed significant correlations between baseline CSF, but not blood, apoB levels and both CSF t‐tau (R2 = 0.23, P < 0.0001) and P‐tau (R2 = 0.28, P < 0.0001). Similar associations were observed when using PET flortaucipir‐binding in entorhinal, parahippocampal and fusiform regions. No association was detected between CSF apoB and CSF Aβ42 levels or cerebral Ab deposition. Baseline CSF apoB levels were associated with visuospatial cognitive decline over the course of 6‐8 years (R2 = 0.13, P < 0.02) and alterations in several synaptic proteins in the CSF. Contribution from peripheral apoB was found to be negligible. In ROSMAP, APOB gene expression failed to correlate with either tangle pathology or amyloid plaque deposition.ConclusionCSF apoB markedly associates with early tau dysregulation in asymptomatic subjects and identifies at‐risk individuals predisposed to develop visuospatial cognitive decline over time.
Tools for harmonization of data in World‐Wide FINGERS
Authors: Talton Jennifer W , Fernandez Shane , Garcia Katelyn R , Crivelli Lucia , Snyder Heather M , Lovato Laura , Martins Ralph N , Kivipelto Miia , Mangialasche Francesca , Pérez Kristal Morales , Espeland Mark A 
Published: December 2021

AbstractBackgroundWorld‐Wide FINGERS (WW‐FINGERS) is a global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention (Kivipelto et al., 2020). With over 30 countries conducting studies within the network, harmonizing interventions and data collection wherever possible is a priority. However, study‐specific adaptations are inevitable to accommodate differences in language, culture, and environment. Thus, a single data collection system is not feasible across WW‐FINGERS and opportunities for synergies between study‐specific systems should be explored.MethodREDCap (Research Electronic Data Capture) is a secure, web‐based software platform which supports validated data capture for research studies (Harris et al., 2009). The underlying blueprint for each REDCap project is a ‘data dictionary’ – a .csv file containing all metadata required to recreate case report forms (CRF) for each point of data collection, including variable names and response options. Data dictionaries can be easily exported, shared, and imported into other REDCap instances. This enables utilization of the same overall structure where possible and preserves response options and variable names while making needed adaptations. Within the WW‐FINGERS network, the study to Protect Brain Health through a Lifestyle Intervention to Reduce Risk (U.S. POINTER) developed a REDCap system based on its protocol and shared its data dictionary with two other WW‐FINGERS studies – AUstralian‐Multidomain Approach to Reduce Dementia Risk by PrOtecting Brain Health with Lifestyle Intervention (AU‐ARROW) and LatAm FINGERS (Latin American initiative for lifestyle Intervention to Prevent Cognitive Decline and reduce risk study).ResultAU‐ARROW and LatAm FINGERS are in the process of incorporating relevant pieces of the U.S. POINTER REDCap project into REDCap systems developed for their studies. While the systems are not identical given the different intervention structures, we aim to standardize 50‐75% of the common variables used across the studies.ConclusionUsing REDCap allows each WW‐FINGERS study to develop its own customized system for data capture, while easily standardizing common variable names, response options, and CRFs; along with exporting de‐identified data. As a result, data sharing and analysis across the WW‐FINGERS network can be streamlined. Furthermore, this process may serve as a roadmap for other global consortia’s similar efforts.