bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited cerebral microbleeds effect on regional magnetic susceptibility measured by MRI
Authors: Fazlollahi Amir , Raniga Parnesh , Bourgeat Pierrick , Yates Paul A , Bush Ashley I , Salvado Olivier , Ayton Scott 
Published: December 2020

AbstractBackgroundCortical iron accumulation has been reported as a pathological feature of Alzheimer’s disease (AD). The cause of cortical iron elevation in AD is unknown but may be contributed by hemosiderin deposits in cerebral microbleeds (CMBs) that frequently occur in this disease. In this study, we investigate the impact of CMBs (which are more frequent in AD) on the magnetic susceptibility of the surrounding brain tissue.MethodThirty‐two cross‐sectional MRI scans from the Australian Imaging, Biomarker and Lifestyle (AIBL, www.aibl.csiro.au) study were found to have 77 definite CMBs by manual assessment of susceptibility weighted images (SWI). The subjects were classified as cognitively normal (CN; N=17; Age:77.4 ± 6.1; CMB:48), mild cognitive impairment (MCI; N=10; 79.1±7.3; 18), or AD (N=5; 77.6±6.2; 11). Quantitative susceptibility mapping (QSM; an MRI technique that is sensitive to iron) was used to estimate iron content in the tissue surrounding the microbleed in four concentric spheres of increasing radius of 1 voxel (∼0.93x0.93x1.75 mm3; regions R1‐4) starting from the boundary of each microbleed. Furthermore, regions R1‐4 were compared to QSM measured in mirror regions of the opposing hemisphere.ResultThe results are presented in Figure 1. The ipsilateral side had significant elevation of QSM in the microbleed compared to the same region on the contralateral side (P<1 x 10‐10). The immediate region surrounding the microbleed, R1, also had elevated QSM signal in the ipsilateral side compared to the contralateral side (P=0.0083). However, there was no difference between ipsilateral and contralateral QSM values in regions R2‐4. These data indicate the QSM is elevated in the brain tissue in the immediate vicinity of the microbleed, but this does not extend beyond 1 voxel.ConclusionThe local changes in susceptibility due to CMBs could be caused by iron from the CMBs extruding into the surrounding tissue, or it could be caused by partial voluming effect. Regardless, the susceptibility change in this relatively small proportion of tissue suggests that increased iron deposition observed in more widespread cortical regions in AD may be due to a more generalized process or very small lesions below the threshold of detection of these imaging modalities.
Peripheral and total circulating extracellular vesicle levels of advanced glycation end‐products and RAGEs as possible biomarkers for mild cognitive impairment and Alzheimer's patients
Authors: Haddad Mohamed , Khedher Morgane , Khedher Mohamed Raâfet Ben , Fulop Tamas , Ramassamy Charles 
Published: December 2020

AbstractBackgroundAdvanced glycation end‐products (AGEs), their precursors methylglyoxal (MG), glyoxal (GO) and their receptors RAGEs are known to be involved in the pathophysiology of Alzheimer’s disease (AD). The aim of our study was to evidence the presence of RAGEs and glyoxalase‐1 (GLO‐1), the main enzyme involved in the degradation of MG, in the circulating extracellular vesicles (pEVs) from control subjects, mild cognitive impairment (MCI) and AD patients.MethodEVs were isolated from plasma of control, MCI and AD subjects at different stages of the disease (early , moderate and severe). Their size, shape and density were characterized. The presence of EVs specific proteins TSG101, CD63, GAPDH were confirmed by Western Blot. MG and GO levels in serum were determined by HPLC. In addition, serum Pentosidine and CML levels were determined by competitive ELISA.ResultOur data showed lower levels of RAGE in pEVs from MCI, early and moderate stage of AD patients as compared to the severe stage of AD patients. GLO‐1 levels in pEVs were significantly decreased in early AD as compared to controls and MCI. Interestingly, RAGEs and GLO‐1 levels in pEVs were correlated with the clinical cognitive scores. MG and GO levels in serum were higher in MCI and receiver‐operating characteristic curves analysis showed that serum MG levels have higher sensitivity to differentiate MCI from controls but not from AD. Meanwhile, serum GO levels differentiate MCI from control and AD groups. The levels of CML in albumin‐free serum proteins were higher in the early stage of AD while, the levels of pentosidine remained unchanged and were negatively correlated with the clinical cognitive scores MMSE and MoCA. In contrast, the levels of N‐(1‐carboxymethyl)‐L‐lysine in pEVs were lower in the moderate stage of AD.ConclusionLevels of some AGEs and RAGEs in serum and in total circulating EVs could be used as possible biomarkers for MCI and AD. This work was supported by the Chaire Louise & André on Alzheimer’s disease, Foundation Armand‐Frappier (CR) and CIHR grant (TF).
Mapping behavior symptoms in dementia using passive radio sensing
Authors: Vahia Ipsit V. , May Rose , Kabelac Zach , Owoyemi Praise , Hoti Kreshnik , Munir Usman , Katabi Dina 
Published: December 2020

AbstractBackgroundBehavioral and Psychotic Symptoms in dementia (BPSD) are associated with negative outcomes including increased mortality and morbidity, increased cost of care and caregiver burnout. Newer technologies are leading to a greatly enhanced ability to monitor and predict these symptoms using passive sensing and sophisticated analytics that rely on signal processing and potentially machine learning. In this study we utilized a novel passive sensing approach supported by AI to demonstrate how highly specific behavioral phenomena can be detected in real time with a need for limited in‐person supervision and monitoring.MethodsEmerald is a device developed at MIT for in‐home, non‐intrusive patient monitoring. The device transmits low‐power radio signals (100x lower power than WiFi) and monitors the reflection of these signals from people/their environment to map behavioral information. Signal data are uploaded to the cloud where customized machine learning algorithms process the data to extract gait speed, sleep patterns, spatial location, respiration Subject: We installed the device in the rooms of 13 adults with Dementia in an assisted living facility outside Boston. We measured the subjects’ behavior continuously for 3 months. Sensor data findings were compared to staff observations around specific behavior phenomena. Our goal was to demonstrate Emerald’s ability to accurately capture a range of BPSDResultsOver the course of the study, we identified a range of behavioral phenomena using the sensor, that were verified by staff and validated by standardized behavioral measures. These represent positive and negative states of activation. The sensor also captured the impact of pharmacotherapy.ConclusionThis study demonstrating the feasibility of an AI‐backed passive sensor‐based device to accurately phenotype a range of behavioral phenomena. Our initial findings demonstrate that this technology can identify movement‐based behavior symptoms in a manner comparable to the current standard for measuring behaviors.
Cognitive and imaging impacts of left ventricular hypertrophy in people with type 2 diabetes
Authors: Restrepo Carolina , Patel Sheila , Werden Emilio , Khlif Mohamed Salah , Singleton Rebecca , Bird Laura J. , Ekinci Elif , MacIsaac Richard , Srivastava Piyush , Burrell Louise , Brodtmann Amy 
Published: December 2020

AbstractBackgroundOlder adults with type 2 diabetes mellitus (T2DM) are at an increased risk of cognitive decline and dementia. Left ventricular hypertrophy (LVH) is prevalent in T2DM and is independently associated with cognitive decline. We conducted a study to establish whether T2DM patients with LVH have increased rates of brain atrophy and cognitive impairment.MethodsThirty‐seven cognitively healthy adults (50 years and older) with T2DM were divided into those with (n=13) and without (n=24) LVH. All participants completed neuropsychological assessments, health‐and‐lifestyle questionnaires, 24‐hour ambulatory blood pressure monitoring, an echocardiogram and a 3T‐MRI scan. FreeSurfer (version 6.0) was used to estimate total brain volume (TBV), mean cortical thickness and subcortical volumes, including the thalami and caudate nuclei. TBV was expressed as a percentage of intracranial volume. Averages between left and right volumes were calculated for subcortical structures. Left ventricular mass was indexed to height2.7 using the American Society of Echocardiography criteria. LVH was defined as >49g/m2.7 for males and >45g/m2.7 for females. Three cognitive domains (visuospatial skills, verbal memory and executive functions) were derived through factor analysis. These variables were used to compare cognitive performance between individuals with and without LVH.ResultsThere was a higher percentage of women (x2=11.01, df=1, p<0.01) in the LVH group. No differences in cortical thickness and TBV were found between groups. The LVH group showed significantly lower volume in the cerebellar cortex (F(1, 32)=5.25 p=0.029) and in the amygdala (F(1, 32)=6.24 p=0.018) after correcting for sex, age, blood pressure and BMI when compared to the no LVH group. Significant differences were found in the visuospatial skills factor (F(1, 43)=4.09; p = 0.049), with the LVH group performing worse than the no LVH group.ConclusionsThe presence of LVH in individuals with T2DM was associated with atrophy in the cerebellar cortex and in the amygdala, as well as with poorer visuospatial function.
Modulation of amyloid deposition and neuroinflammation by the microbiome
Authors: Sisodia Sangram S. 
Published: December 2020

AbstractBackgroundAnimal models of Alzheimer’s disease (AD) recapitulate the severe amyloidosis and neuroinflammation that is evident in the human disease. It is now well established that inflammation associated with amyloid deposition reflects the activation of astrocytes and microglia in response to injury, but the role of peripheral tissues and more importantly, the microbiota in regulating innate immunity that in turn leads to CNS dysfunction has not, to date been defined. We have tested the hypothesis that the composition of the intestinal microbiome plays a key role in modulating neuro‐inflammation that will ultimately influence amyloid deposition in two established mouse models of Aβ‐amyloidosis.MethodsWe orally administered a combination of antibiotics to induce rapid and sustained alterations in gut microbial populations in two mouse models of amyloidosis. The antibiotic cocktail was administered either postnatally or throughout the lifetime of the animal prior to cull and we employed IHC, biochemical and molecular assays to evaluate amyloid deposition and neuroinflammation in the mouse models. Newly‐generated germ‐free mouse models are being evaluated.ResultsOur studies indicate that alterations in the microbiome parallel changes in plasma cytokines and chemokines, reductions in amyloid deposition and modulation of morphological and transcriptional landscapes of microglia. These effects are unique to male, but not female animals.ConclusionsOur studies reveal an unexpected, but significant alteration in amyloid deposition and microglial phenotypes in the brains of male transgenic mice upon treatment with orally administered antibiotics. Acknowledgments: This work was supported by Cure Alzheimer’s Fund (CAF) Open Philanthropy Fund, Alzheimer’s Association and Good Ventures Foundation. SSS is a paid Consultant of AZTherapies Inc.
Capturing longitudinal impacts on cognition following stroke in rodent models using touchscreen testing
Authors: O'Brien Katrina R , Brait Vanessa H , Jackman Katherine A , Ermine Charlotte M , Thompson Lachlan H , Brodtmann Amy , Nithianantharajah Jess 
Published: December 2020

AbstractBackgroundUp to two thirds of ischaemic stroke survivors develop cognitive impairment, predominantly impacting executive and attentional processing. Animal models are essential for effective translation and development of therapies. However, accurately modelling cognitive dysfunction in animal models of stroke has been limited. To address this, we aimed to longitudinally examine changes in attentional processing, spatial working memory and processing speed using two rodent ischemic injury models: the middle cerebral artery occlusion (MCAO) in C57BL/6J mice and the endothelin‐1 injury in Long Evans rats.MethodUsing the rodent touchscreen cognitive platform, we assessed attention in mice and rats employing the Continuous Performance Task (CPT) paradigm, and spatial working memory in mice using the trial unique non‐matching to location (TUNL) paradigm. Cognitive performance in adult mice and rats was assessed before inducing stroke, and at 4, 12, 24, 36 and 48 weeks post‐injury.ResultMice exposed to MCAO showed robust, long‐lasting deficits in attentional processing and spatial working memory post‐stroke. In comparison, we observed no changes in attentional processing following endothelin‐1 injury to the motor cortex in rats.ConclusionOur findings provide the first evidence for longitudinal cognitive changes in a rodent model of stroke, recapitulating that observed in the clinic. Our results identify a valuable model and behavioural approach to advance mechanistic understandings of the trajectory of cognitive dysfunction following stroke, and provide a platform with which to identify novel therapies. Moreover, our work further strengthen the need for preclinical animal studies to assess different species and injury models that are critically needed for better modelling clinical stroke and truly enabling the translation of research targeting cognitive symptoms.
Subjective cognitive decline is associated with neurocognition in the SOL‐INCA study
Authors: Zlatar Zvinka , Tarraf Wassim , Chai Albert , Vasquez Priscilla M , Marquine Maria J , Lipton Richard B , Gallo Linda , Khambaty Tasneem , Zeng Donglin , Youngblood Marston , Estrella Mayra L , Isasi Carmen R , Daviglus Martha , Gonzalez Hector M 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) is the experience of cognitive decline not yet apparent through formal neuropsychological testing. SCD is required to meet clinical criteria for mild cognitive impairment (MCI) and is a potential early risk marker of neurocognitive changes. Despite increased risk of cognitive decline in US Hispanics/Latinos, SCD research in this group is lacking. We investigated if SCD is cross‐sectionally associated with objective neurocognitive performance in SOL‐INCA, a large community‐based sample of diverse Hispanics/Latinos.MethodParticipants (N=5,282) were age 50+ and without reported dementia. The Everyday Cognition Short Form (ECog‐12) scale measured SCD. A global score, as well as memory and executive ECog‐12 sub‐scale scores, were calculated by averaging across z‐scores of individual items assessing memory and executive functional abilities (all items were averaged for the global score). Objective neurocognitive function was measured with tests of memory (Spanish English Verbal Learning Test‐Sum and Recall scores) and executive functions (word fluency, Trail Making Test A & B, and Digit Symbol Substitution scores). Memory, executive, and global neurocognitive composite scores were created by averaging across z‐scores for each cognitive domain listed above, and across all tests for the global composite. Regression models interrogated associations of ECog‐12 (global and sub‐scale scores) with their respective objective neurocognitive function counterparts (global cognition, memory, and executive function neurocognitive composite scores), adjusting for age, sex, education, Hispanic/Latino background, depression, anxiety, and cardiovascular risk factors.ResultWomen comprised 53% of the sample and 25% of the sample were age 70+. Global score, memory, and executive sub‐scale ECog‐12 scores were significantly associated with global (B= ‐0.14), memory (B= ‐0.11), and executive function (B= ‐0.11) neurocognitive composite scores respectively (all p‐values <.001), such that higher ECog‐12 scores (more complaints) were related to lower neurocognition for all three neurocognitive composites.ConclusionContrary to previous research in non‐Hispanic Whites, SCD is associated with concurrent objective neurocognitive function among Hispanic/Latino community‐dwelling adults. SCD may have utility as an early risk marker in this population. More research is needed to determine the predictive value of SCD reporting within Hispanics/Latinos as well as the utility of informant’s report in predicting neurocognitive change.
Functional network disconnection precedes structural atrophy in longitudinally confirmed multi‐domain amnestic MCI
Authors: Broadhouse Kathryn M , Winks Natalie J , Summers Mathew J 
Published: December 2020

AbstractBackgroundIt is widely accepted that numerous neurological changes occur prior to dementia onset, with recent work suggesting that aberrant functional neurocircuitries arising prior to significant cognitive deficits. However, the use of unrefined mild cognitive impairment (MCI) diagnostic criteria in many studies has hampered the investigation of biomarker relationships.MethodPilot structural and resting‐state functional MRI data were acquired in healthy controls (HC), longitudinally confirmed multi‐domain amnestic‐MCI (mdaMCI) and mild AD (mAD). Group differences in cortical thickness, hippocampal volume and functional connectivity were investigated.ResultHippocampal subvolumes differentiated mAD from HC and mdaMCI. Functional decoupling of fronto‐temporal networks implicated in memory and executive function differentiated HC and mdaMCI. Decreased functional connectivity in these networks was associated with poorer cognitive performance scores.ConclusionPreliminary findings suggest the large‐scale decoupling of fronto‐temporal networks associated with cognitive decline precedes measurable structural neurodegeneration and may represent a potential biomarker for disease progression.
GABA and glutamate associate with evidence of preclinical Alzheimer disease in humans: A 7 Tesla MRSI and 11C‐PIB PET study
Authors: Schreiner Simon J. , Kirchner Thomas , Van Bergen Jiri M.G. , Wyss Michael , Steininger Stephanie C. , Gietl Anton F. , Buck Alfred , Treyer Valerie , Nitsch Roger M. , Pruessmann Klaas P. , Hock Christoph , Henning Anke , Unschuld Paul G. 
Published: December 2020

AbstractBackgroundEarly stage Alzheimer disease (AD) is characterized by brain change that includes altered neuronal inhibition and excitation. However, only few data is available for clinical populations. Here, we tested the hypothesis that GABA and glutamate (Glu), the major inhibitory and excitatory neurotransmitters, associate with changes in episodic memory performance, beta‐amyloid (Aß) burden, and genetic risk of AD in old‐aged adults with normal cognition.MethodThirty old‐aged adults underwent genotyping of the apolipoprotein E epsilon 4 allele (APOE4), MRI and MRSI at 7 Tesla (7T) for estimating GABA and Glu levels (referenced to creatine) in grey and white matter of the posterior cingulate and precuneus region, positron emission tomography with 11C‐Pittsburgh compound‐B for measuring Aß burden, and cognitive testing at two time points for assessing longitudinal change in verbal episodic memory performance.ResultHigher levels of GABA and Glu were associated with higher Aß burden (GABA: ß=0.59; p=0.005; R2=0.41; Glu: ß=0.57; p=0.006; R2=0.30), which was particularly evident in APOE4 carriers (significant interaction of Aß burden and APOE4; GABA: ß=0.93; p<0.001; R2=0.80; Glu: ß=0.81; p<0.001; R2=0.59). GABA classified subjects with high vs. low PiB‐SUVR with good accuracy (AUC=0.77; Figure 1). APOE4 and high Aß burden were associated with declining performance at the Verbal Learning and Memory Test (VLMT), immediate recall. However, these associations were attenuated by GABA and Glu, which both associated with VLMT decline (GABA: ß= ‐0.48; p=0.015; R2=0.18; Glu: ß= ‐0.41; p=0.024; R2=0.15; Figure 2). These associations, however, did not survive adjustment for age, sex and education. All findings were exclusively observable for grey and not white matter levels of GABA and Glu.ConclusionOur findings may provide clinical evidence of higher inhibitory and excitatory capacity associated with episodic memory decline, genetic risk and pathology of AD.
The twelve months’ follow‐up, second version, after an intervention using a rehabilitation program of physical and cognitive rec‐xercise (REPCREC) for the elderly with mild cognitive impairment (MCI)
Authors: Kanemaru Akiko , Kato Takayuki , Honda Takuya , Hiraoka Tomo , Kawaji Yoshie , Makita Ayaka , Kuwata Naoya , Shimizu Aya , Higuchi Wakana , Sugawara Yasuhiro , Uemura Honoka , Yamazaki Ritsuko , Kanemaru Kazutomi 
Published: December 2020

AbstractBackgroundWhether our rehabilitation program of physical and cognitive Rec‐Xercise (REPCREC) for the elderly with MCI can bring any difference in cognition and QOL.MethodSubjects are sixty‐nine cases, out of 73 enrolled individuals for more than three years, have undergone our evaluation and intervention program (REPCREC). The subjects have been divided into four groups; group A has taken the cognitive REPCREC, group B physical REPCREC, group C both cognitive and physical REPCREC and group D control. The design of this study is a non‐randomized controlled trial. Three intervention groups have received the each session once per week up to 12 times. Before and after the intervention, and, three, six and twelve months after the intervention, we have evaluated the following items: physical function, Geriatric Depression Scale, POMS2, Visual analog scale (VAS‐1: healthy life, VAS‐2: satisfaction), neuropsychological tests [MMSE, RBMT, TMT, Ravenʼs Colored Progressive Matrices (RCPM), Rey‐Osterrieth Complex Figure Test (ROCF), story retention, coding and Miyake's paired verbal associate learning test (MPVALT)]. A one‐day booster program has been provided at the time of evaluation. For statistical analysis, Fisher's exact test and Kruscal‐Wallis test for the baseline data, and linear mixed model (LMM) analysis and Friedman’s test for the prolonged effect of REPCREC have been performed.ResultsThe median age 79.0 years old, median MMSE score 28.0 points, the number of each group is A 22, B 22, C 25, and D 7cases. At the baseline, no difference between groups. LMM analysis revealed the significant difference in RCPM, ROCF (recall), MPVALT (non‐related), MPVALT (related), coding and VAS‐2 (respectively p=0.000, 0.000, 0.000, 0.001, 0.011 and 0.006). Friedman's test showed significant difference in RCPM of group A (p=0.046) and C (p=0.042), ROCF (recall) group C (p=0.022), VAS‐2 of group A (p=0.013) and C (p=0.011), MPVALT (non‐related) of group A (p=0.007), MPVALT (related) of group A (p=0.016) and C (p=0.048).ConclusionsThe program REPCREC showed the prolonged effects on non‐verbal intelligence, visuospatial abilities, memory, attention, planning, working memory etc. [(RCPM), ROCF (recall), MPVALT] in group A and C comparing with control in the elderly with MCI.