bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between low‐value care treatments and patient‐centered outcomes of people with dementia: A cross‐sectional analysis
Authors: Platen Moritz , Raedke Anika , Wucherer Diana , Thyrian Jochen René , Mohr Wiebke , Scharf Annelie , Mühlichen Franka , Hoffmann Wolfgang , Michalowsky Bernhard 
Published: December 2021

AbstractBackgroundRapidly increasing healthcare expenditures are a global healthcare challenge. Parts of these costs are caused by an overtreatment of patients or low‐value care (LvC), which is defined as care unlikely to provide a benefit to the patient or likely to provide harm. However, there is currently a lack of evidence about the prevalence of LvC and its association with patient‐reported outcomes in people living with dementia (PwD).MethodThe analysis was based on the baseline data of the DelpHi‐trial, including 516 community‐dwelling PwD. LvC were identified by a systematic review of dementia‐specific evidence‐based guidelines, "do not do" recommendations of initiatives, like “Choosing Wiseley”, and lists of inappropriate medication for the elderly. The association of LvC treatments with health‐related quality of life (HRQol), assessed by using the SF‐12 and the Quality of life in Alzheimer´s diseases, and hospitalization were analyzed using multiple regression models.ResultThe study revealed that 159 PwD (31 %) received at least one LvC treatment. They had, on average, less cognitive impairment and less functional impairment than those without LvC. PwD who received LvC had a lower quality of life (b=‐0.08; CI95% ‐0.14 – ‐0.02) and were more likely to be hospitalized (OR=2.11; CI95% 1.30 – 3.41). The lower HRQol was attributed to the measured sedatives and hypnotics (B=‐0.21; CI95% ‐0.34 – ‐0.08). The higher odds for hospitalization could be caused by antidepressants (OR=2.86; CI95% 1.10 – 7.46) and antihypertensive drugs (OR=4.09; CI95% 1.20 – 13.92).ConclusionLvC could reduce patients' HRQoL and increase the risk of hospitalization. More research is needed to evaluate if innovative approaches, like digital health applications, are useful to identify and reduce LvC within primary care and if this could improve PwD HRQoL and reduce hospitalizations.
Developing a consensus protocol for genetic testing in frontotemporal dementia
Authors: Greaves Caroline V , Lahiri Nayana , Rohrer Jonathan D ,   The Genetic Frontotemporal Dementia Initiative (GENFI) and UK Predictive Testing Consortium
Published: December 2021

AbstractBackgroundFrontotemporal dementia (FTD) is genetic in around 30% of people. The aim of the study was to develop a consensus protocol for genetic testing in FTD.MethodsA Delphi methodology was used to achieve consensus recommendations from an international consortium of FTD and neurogenetics specialists. Participants were presented with a number of scenarios involving an asymptomatic individual from a family with a history of FTD but no known genetic mutation, who is requesting predictive testing. Consensus was defined as a recommendation being selected by >80% of respondents.Results1) If an affected relative is alive and able to consent for diagnostic testing, a sample should be taken to ascertain whether there is a genetic form of FTD in the family before the asymptomatic individual can pursue predictive testing. 2) In the case where the affected relative is alive but unable to consent to diagnostic testing, experts decided that a blood or saliva sample could be taken if possible, and with the family’s agreement diagnostic testing could be performed to ascertain whether a mutation is present prior to predictive testing. 3) When there is no living affected relative but a sample of DNA or tissue has been stored, experts agreed that diagnostic testing should be performed on the sample, independent of family history, prior to offering predictive testing. 4) In the case where there is no living relative and no stored DNA or tissue but there is known pathology in a deceased family member that is pathognomonic for a specific genetic form of FTD, the consensus was to perform predictive testing based on that pathology. 5) Where there is no stored sample available, experts were in agreement that predictive testing should not be offered.ConclusionsThis revised protocol will provide guidance to clinicians for FTD‐specific genetic testing.
Pattern of progression in MAPT‐related frontotemporal dementia: Results from the GENFI study
Authors: Todd Emily G , Peakman Georgia , Cash David M , Convery Rhian S , Russell Lucy L , Thomas David L , van Swieten John C , Jiskoot Lize C. , Seelaar Harro , Borroni Barbara , Galimberti Daniela , Sanchez‐Valle Raquel , Laforce Robert , Moreno Fermin , Synofzik Matthis , Graff Caroline , Masellis Mario , Tartaglia Maria Carmela , Rowe James B , Vandenberghe Rik , Finger Elizabeth , Tagliavini Fabrizio , de Mendonca Alexandre , Santana Isabel , Butler Christopher , Ducharme Simon , Gerhard Alexander , Danek Adrian , Levin Johannes , Otto Markus , Sorbi Sandro , Le Ber Isabelle , Pasquier Florence , Rohrer Jonathan D , Bocchetta Martina ,   Genetic Frontotemporal Dementia Initiative (GENFI)
Published: December 2021

AbstractBackgroundMutations in MAPT are associated with frontotemporal dementia (FTD), but little is known about the progression in its early stages. We aimed at identifying the presence of early brain changes in MAPT mutation carriers.MethodWe included 3T MRIs from 84 MAPT carriers [27 symptomatic: mean(SD) age 58(8) years; 57 presymptomatic: 40(11) years] from the Genetic FTD Initiative (GENFI) and from 77 age‐matched non‐carrier healthy controls (44(14) years). Based on their expected years to symptom onset (EYO), we divided the presymptomatic carriers into early (n=35, <‐10 years) and late (n=22, >‐10 years) groups.First, we performed voxel‐based morphometry (VBM) comparing 24 symptomatic carriers with 32 controls to identify the regions of interest (ROIs) which were atrophic in the symptomatic stage of MAPT. We then used automated and manual segmentations to extract these ROI volumes in all carriers. To remove the effect of age, gender, total intracranial volume and scanner type, we transformed the volumes into w‐scores, considering the controls as the reference group. A w‐score of <‐1.28 (corresponding to the 10th percentile) was considered abnormal.ResultFrom the VBM we identified seven structures significantly atrophic in symptomatic carriers: the nucleus accumbens, amygdala, hippocampus, orbitofrontal cortex, temporal pole, anterior insula and hypothalamus.The percentage of early presymptomatic carriers with abnormal w‐scores was 14% for nucleus accumbens and hippocampus, and 20% orbitofrontal cortex. In the late group, 36% showed abnormal amygdala and temporal pole, 27% abnormal hippocampus, 32% abnormal anterior insula and 9% abnormal hypothalamus. In the symptomatic group, the percentages were higher: nucleus accumbens (41%), amygdala, hippocampus and temporal pole (85%), orbitofrontal cortex (56%), anterior insula (93%) and hypothalamus (48%).ConclusionAbnormal limbic regions are a frequent feature in presymptomatic MAPT carriers, showing early structural changes before symptom onset. Further investigations on the associated cognitive and white matter changes are ongoing.
Active diagnostics of dementia in the inland region of Portugal
Authors: Marques Ermelinda Maria Bernardo G , Paiva Teresa , Paulino Manuel , Corte Agostinha ,   NEUROQUALYFAM Group
Published: December 2021

AbstractBackgroundAccording to Alzheimer Europe (2019), it is estimated that in 2018, there were 8,885,101 people with dementia in Europe (EU‐28), with a prevalence of 1.73%. In Portugal, it is estimated that this figure is 193,516, with a prevalence of 1.88%, surpassing the European trend, since it is expected to almost double the number of cases in 2050 (346,905), reflecting the significant increase of people over 70 years and, specifically over 85. The OECD's “Health at a Glance 2020” report indicates that Alzheimer's and other dementia accounted for 5% of all deaths in 2017.Thus, it becomes relevant to study the magnitude of this problem also at the local level.This study aims to identify and characterize people with dementia in a region of the inland region of Portugal. It is assumed as the first stage of a more comprehensive study on the quality of life of the person with dementia and his/her family, within the framework of the NEUROQUALYFAM Project (0541_NEURO_QUALYFAM_6_E).MethodThis is a cross‐sectional descriptive epidemiological study of people with dementia. The data, provided by health services, refer to the active diagnoses of the disease, according to the International Classification of Primary Health Care ‐ ICPC‐2 (P70 ‐ Dementia) and do not allow to trace any of the individuals.ResultThe total number of people with active diagnosis of Dementia (P70) was in 2019, around 1603 cases, with an increase of 363 cases between 2014 and 2019. The proportion of active diagnoses in the resident population was 1.13%, with higher values in women (0.80% versus 0.33% in men). Most active diagnoses (95.51%) are from people aged 65 years or older, also reflecting the results a higher proportion in the higher age groups, namely 25.02% in the 80–84‐year‐old group and 43.54% in the 85‐year‐old group.ConclusionThe identification and characterization of people with dementia, in the geographic area under study, will now allow the development of the study of the quality of life of these people and their families so that it is possible to implement more specific and targeted strategies for this target population.
Markers of periodontal disease and cognitive decline in a diverse, older cohort
Authors: Nikitin Benjamin , Bahorik Amber L , Mcevoy Claire T , Yaffe Kristine 
Published: December 2021

AbstractBackgroundPrior studies have reported associations between periodontitis, as a proxy for inflammation, and increased risk of cognitive decline and dementia, but findings for specific markers of periodontal disease (PDD) have been inconsistent with the few longitudinal studies in diverse cohorts. The goal of this study was to assess whether measures of PDD were associated with subsequent cognitive decline in a cohort of older Black and white adults.MethodWe studied 967 Black and white adults, aged 70‐79 at baseline (51.8% female and 32.8% Black), enrolled in the Health, Aging and Body Composition study. Participants received a periodontal exam in year 2 which assessed indicators of PDD: gingival index (a rating of gingival inflammation), mean attachment loss, and mean pocket probing depth. Cognitive testing was repeated at baseline, years 3, 5, 8, 10, and 11, and included the Modified Mini‐Mental State (3MS) Examination and the Digit Symbol Substitution Test (DSST). We evaluated the association between PDD, categorized as tertiles, and cognitive decline over 11 years of follow‐up with linear mixed‐effects models.ResultIn unadjusted models, higher gingival index was associated with greater decline on 3MS (high vs. low gingival index β = ‐0.27, 95% CI ‐0.48 to ‐0.05) but not DSST. This relationship remained significant after adjusting for race, sex, education, and socioeconomic status (β = ‐0.26, 95% CI ‐0.48 to ‐0.04). Models stratified by race suggest that this association was stronger among older Black adults (Black: β = ‐0.44, 95% CI ‐0.81 to ‐0.06; white: β = ‐0.13, 95% CI ‐0.40 to ‐0.12). Mean attachment loss and mean pocket probing depth were not consistently associated with cognitive decline.ConclusionGingival index was associated with worse decline in global cognition among Black and white older adults. Further work is necessary to understand other measures of poor oral health as markers of cognitive aging in diverse populations.
Longitudinal hippocampal atrophy in hippocampal sclerosis of aging vs. Alzheimer’s disease
Authors: Li Janice X. , Nguyen Hannah L. , Woodworth Davis C. , Sajjadi S. Ahmad 
Published: December 2021

AbstractBackgroundHippocampal sclerosis of aging (HS) is a common degenerative neuropathology in older individuals and is strongly associated with dementia. HS is characterized by disproportionate hippocampal atrophy at autopsy but cannot be diagnosed during life. Therefore, little is known about the onset and progression of hippocampal atrophy and how it relates with stages of cognitive impairment in individuals with HS. We performed a longitudinal case‐series study of hippocampal atrophy and its progression in participants with HS at autopsy compared with matched participants with Alzheimer’s disease (AD) and those without HS or AD to better understand the longitudinal pattern of hippocampal atrophy in HS.MethodsWe used data from Alzheimer’s Disease Neuroimaging Initiative (ADNI‐1, http://adni.loni.usc.edu/) participants with both 3D‐T1w MRIs and autopsy data. Of 47 total participants, 6 had HS. 12 comparison cases were matched by age, sex, and education: 6 with AD, and 6 with neither HS nor AD (No‐HS/AD). We calculated total hippocampal volume using FreeSurfer v6.0 (https://surfer.nmr.mgh.harvard.edu/fswiki/LongitudinalHippocampalSubfields). We plotted hippocampal volumes with respect to age labeled by cognitive status, and compared average volumes and slopes using paired T‐tests.ResultsParticipant characteristics are shown in Table‐1. Three HS participants also had AD. All except one HS participants had lower hippocampal volumes compared to the matched AD and No‐HS/AD participants (Figure‐1). HS3 participant maintained a high hippocampal volume and normal cognition throughout follow‐up. When excluding participants with normal cognition at the time of imaging (HS3, N5), paired T‐tests for average hippocampal volume trended towards significance (HSvsAD P=0.060, HSvsNo‐HS/AD P=0.12), but there were no significant differences in slopes of volume change with age (Figure‐2).ConclusionThe results of this case‐series suggest that individuals with HS have MRI detectable smaller hippocampi than individuals with AD or other pathologies at corresponding stages of cognitive impairment. Our findings also suggest that hippocampal atrophy may begin several years before dementia onset in individuals with HS, supporting the potential utility of hippocampal atrophy as an early biomarker for HS.
Cognitive decline in possible vascular cognitive impairment (VCI): Does the form of vascular brain injury matter?
Authors: Boomsma Jooske , Exalto Lieza G. , Barkhof Frederik , Leeuwis Anna E. , Prins Niels D. , Scheltens Philip , Teunissen Charlotte E. , Weinstein Henry C. , Biessels Geert Jan , van der Flier Wiesje M ,   TRACE‐VCI study group
Published: December 2021

AbstractBackgroundPatients presenting at a memory clinic with possible VCI include a heterogeneous population in terms of cognitive profile, vascular brain injury and prognosis. Little is known about the trajectories of cognitive decline on cognitive test performance in relation to the different forms of vascular brain injury.MethodWe included 474 memory clinic patients(age 68(±8.2) years, 44% female, mean MMSE 25.9(±2.9), 212(44.7%) patients with dementia) from the prospective TRACE‐VCI cohort study with possible VCI; cognitive complaints and vascular brain injury on MRI. We assessed cognitive functioning at baseline and follow‐up(mean follow‐up time 2.5(±1.4) years, total of 1176 neuropsychological tests) including the Rey Auditory Verbal Learning Test(RAVLT) immediate and delayed recall(memory), the Trail Making Test(TMT) A and B(attention and executive functioning, respectively), category fluency(language) and MMSE. Linear mixed models were used to evaluate the effect of different forms of vascular brain injury on cognitive decline. Models included(dichotomized) terms for vascular brain injury(infarct(s), lacune(s), white matter hyperintensities(WMH), microbleed(s)), time and vascular brain injury*time. All models were adjusted for sex, age, diagnosis (dementia versus no dementia), education and medial temporal lobe atrophy(MTA) score(dichotomized as ≥1.5). Also, the models were evaluated in patients with a positive(+CSF‐AD) and negative(‐CSF‐AD) biomarker CSF Alzheimer profile.ResultVascular brain injury(multiple forms in one patient possible) consisted of infarct(s) in 54(11.4%), lacune(s) in 108(22.8%), moderate/severe WMH in 212(44.7%) and microbleed(s) in 203(42.8%) patients. In 164(54.3%) patients the MTA score was ≥1.5. We found no association between any form of vascular brain injury and baseline cognition. Infarct(s) showed an association with worsening on the TMTB(β;30.19,p=.00), especially in patients with a –CSF‐AD(β;65.93,p=.00). This effect was not found in patients with a +CSF‐AD(β;‐25.24,p=.18). Lacune(s) were associated with a rate of decline in immediate memory(β;1.62), delayed recall(β;.33), category fluency(β;.44) and MMSE(β;.46;all p<0.05). Infarct(s) were associated with a slower rate of decline on category fluency(β;.96,p=.01). We found no association between WMH, microbleed(s) and rate of cognitive decline.ConclusionIn patients with possible VCI, infarct(s) were associated with steeper decline in executive functioning, especially in patients with a –CSF‐AD. Counterintuitively, the presence of lacune(s) and infarct(s) predisposed for a more favorable trajectory in memory.
Remote identification of MCI using self‐ and study partner‐report subjective cognitive decline in the Brain Health Registry
Authors: Nosheny Rachel L , Jin Chengshi , Banh Timothy , Ashford Miriam T. , Camacho Monica R , Mackin R Scott , Truran‐Sacrey Diana , Flenniken Derek , Neuhaus John 
Published: December 2021

AbstractBackgroundEfficient identification of older adults with Mild Cognitive Impairment (MCI), including MCI due to AD, is a pressing challenge. Remote methods to accurately identify older adults with MCI are a promising approach. Subjective cognitive decline (SCD), reported by individuals and their study partners, can be efficiently collected remotely.MethodsIn 1286 older adults in the Brain Health Registry (BHR, Table 1), using logistic regression, we determined the accuracy of online self‐report mood (Geriatric Depression Scale Short Form, GDS), family history of AD, Everyday Cognition Scale (ECog) as a measure of SCD, and Cogstate Brief Battery one card learning (OCL) accuray to distinguish (1) Cognitively‐unimpaired (CU) from MCI, and (2) CU from b‐amyloid (Ab)+ MCI. In a subset of 289 participants with enrolled study partners, we measured the contribution of study partner‐report SCD to predicting diagnostic category, and the correlation between self‐ and study partner‐report SCD. Models covaried for age, gender, and education level.ResultsSelf‐ and study partner‐report SCD scores were moderately correlated (r=0.44); associations between the two measures were significantly lower in participants with higher GDS scores, indicating more depressive symptoms (p=0.03). Models including self‐ and study partner‐report SCD and Cogstate OCL scores had the highest accuracy for distinguishing CU from all MCI, as well as CU from Ab+ MCI (AUC=0.90 for CU vs MCI; AUC=0.93 for CU vs Ab+ MCI). Models excluding study partner‐report SCD had moderate accuracy at diagnostic classification (AUC=0.81 for CU vs MCI; AUC=0.83 for CU vs Ab+ MCI). Models excluding all SCD measures, and instead relying on OCL accuracy scores, had lower accuracy (AUC=0.73 for CU vs MCI; AUC=0.76 for CU vs Ab+ MCI). Model outputs are summarized in Table 2.ConclusionsRemotely‐collected self‐ and study partner‐report SCD accurately distinguish CU from MCI, as well as CU from biomarker positive MCI. SCD measures perform well in identifying MCI, even in the absence of objective cognitive measures. Results support utilization of remote SCD measures to identify older adults for prodromal AD clinical trials, and who are suitable candidates to receive future anti‐amyloid therapeutics.
Associations between cerebrospinal fluid markers of neuroinflammation and longitudinal measurements of white matter lesions
Authors: Gertje Eske Christiane , Janelidze Shorena , van Westen Danielle , Cullen Nicholas , Palmqvist Sebastian , Hansson Oskar , Mattsson‐Carlgren Niklas 
Published: December 2021

AbstractBackgroundThe interplay between neuroinflammation and small vessel disease in the early stages of neurodegenerative disease is unclear. Here, we tested the association between cerebrospinal fluid (CSF) levels of biomarkers reflecting inflammatory processes and white matter lesion (WML) volume over time.MethodWe included 582 cognitively unimpaired (CU) elderly and 279 patients with mild cognitive impairment (MCI). CSF samples were analyzed for interleukin (IL)–6, IL‐7, IL‐8, IL‐15, IL‐16, interferon‐gamma induced protein‐10 (IP‐10), monocyte chemoattractant protein 1 (MCP‐1), intercellular adhesion molecule 1(ICAM‐1), vascular adhesion molecule 1 (VCAM‐1), placental growth factor (PlGF), and fms‐related tyrosine kinase 1 (sFlt‐1) as well as vascular endothelial growth factor (VEGF). WML volumes were measured at baseline, and at 2, 4 and 6 years. Analyses were adjusted for Aβ status, age and gender.ResultIn CU, lower levels of PlGF (β=‐0.02, p=0.027) were associated with increasing WML burden over time. However, in MCI lower levels of PlGF (β=‐0.05, p<0.001), IL‐16 (β=‐0.04, p=0.010), VEGF (β=‐0.03, p=0.012), IL‐6 (β=‐0.04, p=0.005), IL‐8 (β=‐0.03, p=0.016) and MCP‐1 (β=‐0.03, p=0.012), as well as higher levels of sFlt‐1 (β=‐0.03, p=0.034) were associated with longitudinal increase in WML.ConclusionCSF markers mediating angiogenesis, such as PlGF and VEGF, are associated with longitudinal WML volume changes, especially in individuals with MCI.