bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informant's perceptions and objective cognitive decline among Mexican older adults with a history of traumatic brain injury with and without loss of consciousness
Authors: Piña‐Escudero Stefanie Danielle , de Jesús García Aviles Roberto , Chodos Anna H. , Ritchie Christine S. , Avila Jose Alberto 
Published: December 2020

AbstractBackgroundTraumatic Brain Injury (TBI) is extremely common across the lifespan and is an established risk factor for dementia, including Alzheimer's disease. However, the effect of TBI with loss of consciousness (LOC) history on cognitive change with aging and how it is perceived by caregivers are poorly understood.MethodsCross‐sectional study analyzing 1681 community‐dwelling older adults from the MHAS‐Cognitive Aging Ancillary Study. TBI status (control, TBI without LOC and TBI with LOC) was defined by an affirmative answer to the questions: “Have you ever hurt your head or neck in an accident?” and “Did you lost consciousness as a result of the injury?”. Cognition was measured by a global cognitive score (GCS) that comprised the sum of six cognitive domains. Informants' cognitive perception scores were measured with the Community Screening Instrument for Dementia (CSID). For analysis, chi square and ANOVA were used to describe the sample. Linear regression models adjusting for age, sex, years education, number of comorbidities, functionality and depressive symptoms were built to test the association between TBI status and cognitive scores as well as TBI status and CSDI scores.ResultsThe mean age of the population was 68(+8.6) years, 68% were women, the mean of years of education was 5.5(+4.4), and 14.6% had history of LOC. Simple linear regression models showed a positive association between TBI status and GCS status (β=‐0.078, p=0.001). This association was also observed with the following cognitive domains: orientation (β=‐0.053, p=0.28), immediate recall (β=‐0.088, p=<0.001), delayed recall (β=‐0.073, p=0.003), attention (β=‐0.062, p=0.011) and executive function (β=‐0.06, p=0.010). A significant association with CSID scores was also revealed (β=0.131, p=<0.001) and it was the only association that remained significant after adjustment (β=0.073, p=<0.001).ConclusionFindings from this study suggest that TBI with LOC is not independently associated with cognitive scores in older adults. However, TBI with LOC is significantly associated with CSDI scores even after adjustment. Informant's perceptions reflect that LOC might have and influence in the cognitive skills that older adults use in their everyday life that testing could not accurately capture in a population with low education.
Medication‐related problems in older adults with and without preclinical Alzheimer’s disease: A baseline description from the INCREASE study
Authors: Martinez Ashley I. , Eckmann Lynne , Huffmyer Mark , Beech Brooke F. , George Rosmy , Hall Megan , Abner Erin L. , Jicha Gregory A. , Schmitt Frederick A. , El Khouli Riham H. , Moga Daniela C. 
Published: December 2020

AbstractBackgroundOlder adults are susceptible to negative cognitive effects induced by inappropriate medication use.1 Some individuals may accumulate amyloid‐β deposits before symptomatic expression, suggesting preclinical Alzheimer’s disease (pAD). Inappropriate medication use may interact with this neuropathology to hasten symptomatic AD onset. Thus, we designed INCREASE: a randomized controlled trial (RCT) to improve medication use through targeted medication therapy management (tMTM) and ultimately delay AD symptomatic expression.2
MethodsCommunity‐dwelling non‐demented adults ≥ 65 years old who regularly used ≥1 potentially inappropriate medication3 were recruited for the RCT. Board certified geriatric pharmacists reviewed medication lists and identified medication‐related problems (MRPs) at baseline for all participants before conducting the tMTM intervention. Here, we describe this initial medication review, stratified by pAD status. pAD was defined as total brain relative standardized uptake values > 1.4 for PET amyloid.3 Group differences were identified using Student’s t‐tests.Results79 participants were included in this analysis (mean age 73.9 years [SD 5.9]; 66% female). 12.9 (4.9) baseline medication were reported on average, which did not differ significantly between participants with (14.2 [4.8]) and without (12.3 [5.1]) pAD. The most commonly reported medication classes were proton pump inhibitors, antihistamines, non‐steroidal anti‐inflammatory drugs, and vitamins/supplements. On average, 4.9 (SD 2.3) MRPs were identified per participant (389 MRPs total). The most common causes of MRPs were: 1) a medication not appropriate given the participants’ age and/or medical conditions; 2) dose/frequency too high; and 3) untreated medical condition. The most common recommendation by the pharmacist was to deprescribe the problem medication. There were no differences in the number or causes of MRPs based on pAD status.ConclusionNon‐demented older adults enrolled in an MTM RCT used more than ten medications concurrently, with about 5 MRPs identified in each participant. INCREASE will test the hypothesis that deprescribing these inappropriate medications may delay symptomatic AD. Given that the pharmacokinetics and pharmacodynamics of this population puts them at high risk for adverse drug events including cognitive impairment, future work should continue to optimize medication use to prevent cognitive decline. References: 1. Moga DC, et al. Trials. 2019;20(1):806. 2. Jack CR, et al. Brain. 2015;138(12):3747‐3759. 3. American Geriatrics Society. J Am Geriatr Soc. 2015;63(11):2227‐2246.
Left frontal white matter atrophy links to timing mechanisms relevant for apraxia of speech
Authors: Bruffaerts Rose , Schaeverbeke Jolien , Grube Manon , Griffiths Timothy , Sunaert Stefan , Vandenberghe Rik 
Published: December 2020

AbstractBackgroundIn patients with apraxia of speech (AOS), we observed impaired perceptual timing abilities, which lead us to propose a shared mechanism of impaired timing processing underlying both impaired perceptual processing and motor speech output [1]. Given that white matter damage is often observed in AOS, we here investigate whether white matter changes are related to impaired perceptual timing as one possible mechanism underlying AOS.MethodA psychoacoustic and multimodal neuroimaging analysis was performed in 12 patients with the nonfluent variant (NFV) of Primary Progressive Aphasia (PPA) with AOS, 11 patients with the semantic variant and 24 controls. During the four perceptual timing tasks (r1‐r4, [1]), participants had to detect the longer gap in pairs of tones (r1) or in a sequence of tones (r2) or discriminate between rhythmic sequences with a strongly (r3) or weakly (r4) metrical beat. Speech rhythm was quantified in connected speech by means of the normalized pairwise variability index (PVI). Deformation‐based morphometry (DBM) and diffusion tensor imaging (DTI) were acquired on a 3T MRI and processed using CAT12 and MRTRIX3, respectively. We determined Fractional Anisotropy (FA) and Mean Diffusivity (MD) values for the left Aslant tract, which is typically damaged in NFV.ResultSeventy‐five percent of NFV patients displayed impaired perceptual timing, specifically when discriminating between rhythmic sequences (r3‐r4, transformed to z‐scores, Figure 1). Impaired perceptual timing correlated with abnormal vowel lengthening (correlation of r3 and PVI of strong‐weak words: r = 0.65, P = 0.029). Moreover, left frontal white matter volume loss adjacent to the supplementary motor area (SMA) correlated with impaired perceptual timing (r3) in NFV (Figure 2, cluster‐level FWE‐corr. P<.05). MD in the left Aslant tract also correlated with perceptual timing in NFV (correlation with r3: r = 0.82, P = 0.026).ConclusionA shared white matter substrate adjacent to the SMA links impaired perceptual timing and motor speech impairment. Our data indicates that impaired timing may be one of the neurocomputational mechanisms underlying AOS. Moreover, regional variations in left frontal lobe atrophy explain part of phenotypical heterogeneity in NFV. Resource: (1) Grube, Bruffaerts, Schaeverbeke et al., Brain 2016.
Predictors of acceptability and emotional response to computerized neuropsychological assessments in older adults: The CogSCAN Study
Authors: Rossie Matilda , Croot Karen , Allison Karen C. , Brodaty Henry , Crawford John D. , Lee Teresa , Henry Julie D. , Draper Brian , Close Jacqueline , Ong Min Yee , Lam Ben C. P. , Sachdev Perminder S. , Kochan Nicole A. 
Published: December 2020

AbstractBackgroundComputers and related technologies are increasingly used for cognitive assessment. However, few studies have considered older adults’ experience using computerized neuropsychological assessment (CNA), or individual characteristics that may influence acceptability and emotional responses to computerized tests.Method205 community‐dwelling native English speakers aged 60‐95 were randomly assigned to complete two of four CNA batteries: Cogstate, CANTAB, CBS, and NIH Toolbox, on an iPad. After test completion, participants rated their emotions during testing on a Mood Adjective Checklist (MAC) with four subscales ‐ high stress (worried), low stress (relaxed), high arousal (energised), low arousal (tired), and provided ratings of test acceptability. Multiple regression analyses investigated associations of demographics (age, sex, education), cognitive level (MoCA, premorbid ability), subjective memory, mood over the past week (depression, anxiety, stress), computer/technology attitudes and experience, with the four MAC subscales and test acceptability score. Parallel analyses were performed in a subsample of participants also completing a pen‐and‐paper neuropsychological battery (PnP). Potential differences in predictors for CNA and PNP and the influence of potential confounders (PnP yes/no, CNA test pair) were examined.ResultOver half of the participants had considerable experience with computers or tablets (Table 1). Demographics were not significantly related to emotion ratings or test acceptability and were excluded from further analyses. Higher stress over the past week was associated with feeling more worried and tired during test‐taking. Higher premorbid ability was associated with feeling less relaxed (Table 2). Greater computer anxiety, higher premorbid ability and more computer experience were associated with lower CNA acceptability. Although some predictors of PnP acceptability and emotional response differed (Table 3), interactions between predictors and testing mode were non‐significant for all outcome variables (p’s> .05). Inclusion of potentially confounding variables did not alter the overall findings.ConclusionRecent mood, cognitive level, computer attitudes and experience influenced emotions during testing and test acceptability. These relationships and their potential association with CNA and PnP performance will be investigated in future work. Data on emotional response to testing and test acceptability will need to be triangulated with psychometric information about CNA and PnP measures to determine the most suitable test options for individuals.
Decreased cortical thickness in individuals with subjective cognitive decline with and without CSF‐AD‐pathology: Data from the DELCODE Study
Authors: Meiberth Dix U. , Hu Xiaochen , Schild Ann‐Katrin , Spottke Annika , Brosseron Frederic , Buerger Katharina , Fließbach Klaus , Heneka Michael T. , Kilimann Ingo , Laske Christoph , Peters Oliver , Priller Josef , Schneider Anja , Teipel Stefan J. , Wiltfang Jens , Wagner Michael , Düzel Emrah , Jessen Frank ,   DELCODE Study Group
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) without objective performance deficits reflects in some individuals the earliest symptomatic manifestation of Alzheimer’s Disease (AD) at the late preclinical stage1,2. It is crucial to delineate the relationship between SCD, AD‐specific biomarkers and the localization of early neurodegeneration.MethodWe included the baseline‐dataset of the DELCODE‐study3 (n=943), from which 404 subjects (57 AD, 89 mild cognitive impairment (MCI), 171 SCD, and 87 healthy controls (CO)) received both CSF‐biomarker‐assessment (Aβ‐42, total‐tau, phosphorylated‐tau) and structural MRI. Cortical thickness was estimated with the FreeSurfer‐Software‐package version 6.0. ANCOVAs with one between‐subject factor of diagnosis, and age, sex, and scanner‐sites as covariates were calculated for the bilateral entorhinal cortices (EC) and bilateral parahippocampi (PH), respectively. Two‐way ANCOVAs with between‐subject factors of diagnosis (SCD/CO) and CSF‐biomarkers (positive/negative) and the same covariates were calculated for each of the regions of interests (ROIs) and CSF‐biomarkers.ResultSignificant main effects for diagnosis were found for the one‐way‐ANCOVAs for all ROIs (p<0.001; bilateral EC and left PH: HC=SCD>MCI>AD; right PH: HC>SCD>MCI>AD). Two way‐ANCOVA showed significant main effects for diagnosis for the bilateral PH‐thickness (left: p=0.031; right: p=0.013), and an interaction between diagnosis and CSF‐Aß42 for the left PH‐thickness (p=0.022). Post‐hoc analyses showed the interactions were driven by decreased bilateral PH and left EC thickness in SCD subjects compared to CO in the Aβ42 positive subgroups only (p<0.05), not between the Aß42 negative subgroups. Two‐way‐ANCOVA showed also significant interaction effects between the diagnosis and total‐tau, and between the diagnosis and phosphorylated‐tau in the right EC (t‐tau: p=0.011; p‐tau: p=0.004), where SCD subjects had lower right entorhinal thickness than controls in the tau positive subgroups.ConclusionWe found decreased bilateral parahippocampal and left entorhinal thickness in persons with SCD compared to controls in all amyloid‐positive cases. In addition, the right entorhinal cortex seems to be affected in SCD compared to controls in all tau positive cases. These data suggest that, in addition to positive AD pathology indicated by CSF biomarkers, the first clinical symptoms such as cognitive complaints may also indicate early degenerative processes in the course of the disease.
Awareness of cognitive decline and CSF‐biomarkers in memory clinic patients: Results from the DELCODE‐study
Authors: Miebach Lisa , Kleineidam Luca , Peters Oliver , Priller Josef , Buerger Katharina , Teipel Stefan J. , Perneczky Robert , Laske Christoph , Schneider Anja , Heneka Michael T. , Spottke Annika , Wiltfang Jens , Düzel Emrah , Jessen Frank , Wagner Michael 
Published: December 2020

AbstractBackgroundDecreased awareness of cognitive deficits is a common symptom of dementia. Less is known about the evolution of decreased awareness in earlier stages of Alzheimer’s Disease (AD). Recent studies using the discrepancy between self‐ and informant report found reduced awareness in many patients with mild cognitive impairment (MCI), but generally heightened awareness in cognitively normal individuals with Amyloid pathology. In memory clinic samples, patient and caregiver ratings of cognitive decline were associated with AD‐biomarkers. We investigated in the relationship between CSF‐biomarkers, informant ratings and reduced self‐awareness in a large memory‐clinic sample.MethodsWe analyzed data from n=323 patients with available CSF‐biomarkers (age=71.17; SD=5.71) from the DELCODE‐study (n=211 SCD‐patients; n=112 MCI‐patients). Cognitive complaints in five different domains were assessed using a self‐ and informant rated interview form (Miebach et al. 2019). Reduced self‐awareness was calculated using a self‐/informant discrepancy score. The relationship with CSF‐biomarker was examined using linear regression, controlling for demographic variables and objective memory performance. Participants were classified using the ATN‐system for the diagnosis of preclinical AD.ResultsAll patients reported a cognitive decline in at least 3 domains. On average, SCD participants had positive self‐awareness scores (M=1.20; SD=1.87), indicating more self‐ than informant reported decline, while this significantly reversed in MCI (M=‐.514; SD=1.67). In the total sample, the discrepancy was associated with CSF‐Aß‐42 (ß=.213; p<.000), CSF‐t‐Tau (ß=‐.163; p<.005) and CSF‐Aß/tau‐ratio (ß=.232; p<.001). This association was similar in SCD and MCI. Regarding Biomarker profiles, n=66 participants were classified as A+/T+, n=38 as A+/T‐; n=139 participants were classified as A‐T‐N‐ and n=80 as non‐AD‐pathologic change. Participants with an AD‐typical Biomarker profile (A+/T+) had significantly higher informant than self‐ratings of cognitive decline (p<.001) and reduced awareness (p<.003).ConclusionIn memory clinic patients, lower awareness (i.e. relatively less self‐ than informant rated complaints) was associated with CSF‐Aß‐42, t‐Tau and the Aß/tau‐ratio. The relationship with CSF‐Aß42 and Aß/tau ratio was independent from objective memory impairment, showing that in the absence of objective impairment (i.e. SCD stage) informant ratings of cognitive decline are particularly informative. Results support the use of informant ratings in memory clinic samples, and the inclusion of an informant confirmation in the SCD‐plus criteria, specifying which features increase the likelihood of AD‐pathology in SCD.
Diabetes mellitus, HBA1C, and in vivo Alzheimer’s disease pathologies
Authors: Han Dongkyun , Byun Min Soo , Yi Dahyun , Lee Jun Ho , Byeon Gihwan , Joung Haejung , Moon Seok Woo , Sohn Bo Kyung , Lee Jun‐Young , Kim Yu Kyeong , Lee Yun‐Sang , Sohn Chul‐Ho , Lee Dong Young ,   KBASE Research Group
Published: December 2020

AbstractBackgroundAlthough previous studies have reported associations of diabetes mellitus (DM) with cognitive impairment or dementia, the exact pathophysiological links underlying the associations remain incompletely understood. In this context, we aimed to investigate the associations of DM or glycated hemoglobin (HbA1c) with in vivo Alzheimer’s disease (AD) pathologies such as cerebral beta‐amyloid protein (Aβ) deposition and tau deposition.MethodTotal 136 participants (71 cognitively normal, 31 mild cognitive impairment, and 34 AD dementia) from the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study, were included for this analysis. All participants underwent comprehensive clinical and neuropsychological assessment, 11C labelled Pittsburgh Compound B (PiB) positron emission tomography (PET), 11F AV‐1451 PET, magnetic resonance imaging, apolipoprotein E genotyping, and HbA1c measurement.ResultNeither the presence of DM nor HbA1c level was associated with global Aβ deposition after controlling for age, sex, education, vascular risk score (except DM), apolipoprotein e4 positivity, and clinical diagnosis. In contrast, higher HbA1c was significantly associated with lower AD‐signature region tau deposition and the presence of DM showed a trend level association with decreased tau deposition. Additionally, we found significant Aβ deposition x HbA1c (or the presence of DM) interaction effect on tau deposition. While higher Aβ deposition was significantly related to increased tau deposition in lower HbA1c (or DM negative) subgroup, there was no such relationship between Aβ and tau deposition in higher HbA1c (or DM positive) one. Sensitivity analyses including only cognitively normal individuals also showed similar results.ConclusionOur results indicate that DM or higher blood glucose may not contribute to cognitive impairment or dementia via AD‐specific pathologies, especially amyloid deposition. Therefore, other non‐AD pathophysiological contributions including vascular pathologies should be considered. Although being very cautious, high blood glucose may relate to delayed brain tau deposition.
Transcutaneous vagal nerve stimulation effects on the salience network in patients with amnestic mild cognitive impairment
Authors: Williamson John B. , Lamb Damon G. , Porges Eric , Murphy Aidan J. , Cohen Ronald , DeKosky Steve 
Published: December 2020

AbstractBackgroundBetter treatments are needed to improve cognition and reduce the disability associated with MCI and Alzheimer’s disease (AD). Transcutaneous vagal nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms: the vagus projects to the nucleus tractus solitarius (NTS) which in turn projects to the locus coeruleus (LC), the brain’s primary source of norepinephrine (NE). The NTS also projects directly to the hippocampus, as does the LC. Neuropathological data suggest that the LC may be an early site of AD pathology. Thus, tVNS may modify the activity of several networks that are impaired and that progressively deteriorate in patients with MCI and AD.Method24 patients with mild cognitive impairment (MCI) confirmed via diagnostic consensus conference (sources of info: Montreal Cognitive Assessment Test [MOCA], Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ) , Hopkins Verbal Learning Test – Revised [HVLT‐R] and medical record review) were assessed during rest using functional magnetic resonance imaging (fMRI) on a Siemens 3T scanner during tVNS (left tragus, n = 12) or under sham control conditions (ear lobe, n = 12).ResultDuring unilateral left tVNS, patients with MCI showed increased functional connectivity between nodes of the salience network, the anterior cingulate, and the supramarginal gyrus from both the right and left temporal poles.ConclusionIn patients with MCI, tVNS modified cognitively relevant brain networks whose degeneration predicts deterioration in AD. These findings demonstrate afferent target engagement of tVNS which carries implications for noninvasive therapeutic intervention in this population.
Noradrenergic contributions to cognitive decline and treatment potential in progressive supranuclear palsy and Parkinson’s disease
Authors: Rowe James B. 
Published: December 2020

AbstractBackgroundThe Locus coeruleus is the principal source of Noradrenaline to the cerebrum, modulating diverse functions from attentional and behavioural control, learning and perception, arousal and autonomic control. The locus coeruleus is vulnerable to many neurodegenerative disorders, with post‐mortem evidence of early and substantial cell loss in Alzheimer’s disease, Parkinson’s disease (PD) and Progressive Supranuclear Palsy (PSP). The relevance of locus coeruleus pathology and noradrenergic denervation in vivo has come largely from psychopharmacological studies, and PET imaging of the noradrenergic transporter.MethodWe exploited advances in ultra‐high field magnetic resonance imaging at 7T that now provide excellent sensitivity to the loss of neuromelanin containing neurons in the locus coeruleus, enabling quantification of the spatial extent and signal intensity (cf. cell density) in patients. We developed an optimised atlas of locus coeruleus in older adults (>50), and applied this to independent cohorts of patients with idiopathic Parkinson’s disease and PSP (Richardson’s syndrome) with a magnetisation transfer weighted sequence to scan the brain stem at 7T.ResultPatients in both groups showed a marked reduction in locus coeruleus signal intensity, relative to a mid‐pontine reference regions, especially in the caudal locus coeruleus. In Parkinson’s disease, the contrast‐to‐noise of the locus coeruleus correlated with apathy and motor disease severity. A corresponding reduction of noradrenergic cells was confirmed at post‐mortem in a parallel group of patients with PSP, in whom cell loss was proportional to disease severity.Conclusion7T MRI is well tolerated and sensitive to pathology of the locus coeruleus in PSP and PD. We propose the use of 7T‐MRI to quantify the integrity of the locus coeruleus in stratified trials of therapeutic strategies for cognitive and motor control in neurodegenerative disease.