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Cognitive impairment biomarkers

Dennis Chan, Laura Marie Gallaher, Kuven Moodley, Ludovico Minati, Neil Burgess, Tom Hartley
This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images. Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer's disease (AD) and impairment of hippocampal function predates the onset of dementia...
October 13, 2016: Journal of Visualized Experiments: JoVE
Prashanthi Vemuri, David S Knopman, Clifford R Jack, Emily S Lundt, Stephen D Weigand, Samantha M Zuk, Kaely B Thostenson, Robert I Reid, Kejal Kantarci, Yelena Slinin, Kamakshi Lakshminarayan, Cynthia S Davey, Anne Murray
BACKGROUND: Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. OBJECTIVE: To measure the association between kidney function biomarkers and brain MRI findings in CKD. METHODS: In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI)...
October 19, 2016: Journal of Alzheimer's Disease: JAD
Katherine Amy Lin, Colin Rundel, P Murali Doraiswamy
BACKGROUND: Prior studies have noted gender differences in cognition, imaging, and pathological markers in mild cognitive impairment (MCI) subjects. Sex hormone-binding globulin (SHBG), a major controlling factor in the proportion of bioavailable versus bound testosterone and estrogen, has been proposed to contribute to links between hormones and dementia, but has not yet been investigated fully in a prospective biomarker trial. OBJECTIVE: This study examined whether, among subjects with MCI, SHBG levels predict future rate of cognitive decline...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Axel Van Der Gucht, Mehdi Aoun Sebaiti, Eric Guedj, Jessie Aouizerate, Sabrina Yara, Romain Gherardi, Eva Evangelista, Julia Chalaye, Anne-Ségolène Cottereau, Antoine Verger, Anne-Catherine Bachoud-Levi, Emmanuel Itti, Francois Jerome Authier
PURPOSE: Macrophagic myofasciitis (MMF) is an emerging condition with specific muscle lesions characterized by an abnormal long-term persistence of aluminum hydroxide particles within macrophages at the site of previous immunization. Patients present with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. The aim of this study was to characterize brain FDG-PET metabolic abnormalities in MMF patients, and the relation with cognitive dysfunction. METHODS: FDG-PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (mean age, 45...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Rui Gao, Guangjian Zhang, Xueqi Chen, Aimin Yang, Gwenn Smith, Dean F Wong, Yun Zhou
OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD...
2016: PloS One
Emily C Edmonds, Joel Eppig, Mark W Bondi, Kelly M Leyden, Bailey Goodwin, Lisa Delano-Wood, Carrie R McDonald
OBJECTIVE: We investigated differences in regional cortical thickness between previously identified empirically derived mild cognitive impairment (MCI) subtypes (amnestic MCI, dysnomic MCI, dysexecutive/mixed MCI, and cluster-derived normal) in order to determine whether these cognitive subtypes would show different patterns of cortical atrophy. METHODS: Participants were 485 individuals diagnosed with MCI and 178 cognitively normal individuals from the Alzheimer's Disease Neuroimaging Initiative...
October 19, 2016: Neurology
J A Molad, D T Blumenthal, F Bokstein, M Findler, I Finkel, N M Bornstein, S Yust-Katz, E Auriel
Post-radiation leukoencephalopathy is characterized by cognitive impairment and white matter alternations on imaging. Cerebral small vessel disease (SVD) is one of several suggested etiologies. Cerebral microinfarction (CMI) is a recently described marker of SVD. We sought to examine the rate of CMI as a biomarker of ongoing ischemia among patients who underwent brain radiotherapy (RT). 110 patients treated with RT for primary or metastatic brain tumors were enrolled. A total of 685 brain MRI tests performed 1-108 months post-radiation were examined...
October 18, 2016: Journal of Neuro-oncology
Rinko Grewal, Mona Haghighi, Shuai Huang, Amanda G Smith, Chuanhai Cao, Xiaoyang Lin, Daniel C Lee, Nancy Teten, Angela M Hill, Maj-Linda B Selenica
BACKGROUND: There is a need to investigate biomarkers that are indicative of the progression of dementia in ethnic patient populations. The disparity of information in these populations has been the focus of many clinical and academic centers, including ours, to contribute to a higher success rate in clinical trials. In this study, we have investigated plasma biomarkers in amnestic mild cognitively impaired (aMCI) female patient cohorts in the context of ethnicity and cognitive status...
October 18, 2016: Alzheimer's Research & Therapy
D P Devanand
Several recently developed biomarkers of Alzheimer disease (AD) are invasive, expensive, and difficult to obtain in most clinical settings. Olfactory identification test performance represents a noninvasive, inexpensive biomarker of AD that may have predictive accuracy comparable with neuroimaging measures and biomarkers assessed in cerebrospinal fluid. Neurofibrillary tangles in the olfactory bulb are among the earliest pathologic features of AD and are also seen in the projection pathways from the olfactory bulb to secondary olfactory brain regions, including the piriform and medial temporal cortex, orbitofrontal cortex, and other limbic regions...
August 17, 2016: American Journal of Geriatric Psychiatry
Antti J Luikku, Anette Hall, Ossi Nerg, Anne M Koivisto, Mikko Hiltunen, Seppo Helisalmi, Sanna-Kaisa Herukka, Anna Sutela, Maria Kojoukhova, Jussi Mattila, Jyrki Lötjönen, Jaana Rummukainen, Irina Alafuzoff, Juha E Jääskeläinen, Anne M Remes, Hilkka Soininen, Ville Leinonen
OBJECTIVES: Optimal selection of idiopathic normal pressure hydrocephalus (iNPH) patients for shunt surgery is challenging. Disease State Index (DSI) is a statistical method that merges multimodal data to assist clinical decision-making. It has previously been shown to be useful in predicting progression in mild cognitive impairment and differentiating Alzheimer's disease (AD) and frontotemporal dementia. In this study, we use the DSI method to predict shunt surgery response for patients with iNPH...
October 14, 2016: Acta Neurochirurgica
A Ridder, M L T M Müller, V Kotagal, K A Frey, R L Albin, N I Bohnen
OBJECTIVES: Dopaminergic degeneration affects both nigrostriatal projection neurons and retinal amacrine cells in Parkinson disease (PD). Parkinsonian retinopathy is associated with impaired color discrimination and contrast sensitivity. Some prior studies described associations between color discrimination deficits and cognitive deficits in PD, suggesting that contrast discrimination deficits are due, at least in part, to cognitive deficits in PD. We investigated the relationship between cognitive deficits and impaired contrast sensitivity in PD...
October 7, 2016: Parkinsonism & related Disorders
Ashvini Keshavan, Amanda Heslegrave, Henrik Zetterberg, Jonathan M Schott
Biomarkers in Alzheimer's disease (AD) have the potential to allow early and more accurate diagnosis, predict disease progression, stratify individuals and track response to candidate therapies in drug trials. The first fluid biomarkers reflecting aspects of AD neuropathology were identified in cerebrospinal fluid (CSF) in the 1990s. Three CSF biomarkers (amyloid-β 1-42, total tau and phospho-tau) have consistently been shown to have diagnostic utility and are incorporated into the new diagnostic criteria for AD...
October 13, 2016: Molecular Diagnosis & Therapy
Kelly A Mills, Zoltan Mari, Gregory M Pontone, Alexander Pantelyat, Angela Zhang, Nadine Yoritomo, Emma Powers, Jason Brandt, Ted M Dawson, Liana S Rosenthal
BACKGROUND: In Parkinson's disease, the association between objective and patient-reported measures of cognitive dysfunction is unknown and highly relevant to research and clinical care. OBJECTIVE: To determine which cognitive domain-specific Montreal Cognitive Assessment (MoCA) subscores are most strongly associated with patient-reported cognitive impairment on question 1 (Q1) of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)...
September 27, 2016: Parkinsonism & related Disorders
Brenna M Flannery, Donald A Bruun, Douglas J Rowland, Christopher N Banks, Adam T Austin, David L Kukis, Yonggang Li, Byron D Ford, Daniel J Tancredi, Jill L Silverman, Simon R Cherry, Pamela J Lein
BACKGROUND: Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can trigger convulsions that progress to life-threatening status epilepticus. Survivors face long-term morbidity including mild-to-severe decline in memory. It is posited that neuroinflammation plays a key role in the pathogenesis of OP-induced neuropsychiatric deficits. Rigorous testing of this hypothesis requires preclinical models that recapitulate relevant phenotypic outcomes. Here, we describe a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) that exhibits persistent neuroinflammation and cognitive impairment...
October 12, 2016: Journal of Neuroinflammation
Pia Basaure, Fiona Peris-Sampedro, Maria Cabré, Ingrid Reverte, Maria Teresa Colomina
Cholinesterases (ChE) are common targets of organophosphate (OP) pesticides and play a critical role in the pathology of some dementias. While chlorpyrifos (CPF) remains one of the most commonly used OPs in the world, numerous investigations have reported its neurotoxic potential and highlighted behavioral disturbances upon its administration. Rivastigmine currently serves to treat Alzheimer's disease, but it may induce cholinergic overstimulation in non-demented individuals. The present investigation aimed to compare the acute and delayed effects caused by both ChE inhibitors in adult C57BL/6 male mice...
October 9, 2016: Behavioural Brain Research
Bing Cao, Jun Wang, Mahadi Shahed, Beth Jelfs, Rosa H M Chan, Ying Li
Vagus nerve stimulation (VNS) can enhance memory and cognitive functions in both rats and humans. Studies have shown that VNS influenced decision-making in epileptic patients. However, the sites of action involved in the cognitive-enhancement are poorly understood. By employing a conscious rat model equipped with vagus nerve cuff electrode, we assess the role of chronic VNS on decision-making in rat gambling task (RGT). Simultaneous multichannel-recordings offer an ideal setup to test the hypothesis that VNS may induce alterations of in both spike-field-coherence and synchronization of theta oscillations across brain areas in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA)...
October 12, 2016: Scientific Reports
Daihong Liu, Shanshan Duan, Jiuquan Zhang, Chaoyang Zhou, Minglong Liang, Xuntao Yin, Ping Wei, Jian Wang
Type 2 diabetes mellitus (T2DM) has been associated with cognitive impairment. However, its neurological mechanism remains elusive. Combining regional homogeneity (ReHo) and functional connectivity (FC) analyses, the present study aimed to investigate brain functional alterations in middle-aged T2DM patients, which could provide complementary information for the neural substrates underlying T2DM-associated brain dysfunction. Twenty-five T2DM patients and 25 healthy controls were involved in neuropsychological testing and structural and resting-state functional magnetic resonance imaging (rs-fMRI) data acquisition...
2016: Frontiers in Human Neuroscience
Sarah L Aghjayan, Rachel F Buckley, Patrizia Vannini, Dorene M Rentz, Jonathan D Jackson, Reisa A Sperling, Keith A Johnson, Rebecca E Amariglio
BACKGROUND: Converging evidence suggests that subjective cognitive concerns (SCC) are associated with biomarker evidence of Alzheimer's disease (AD) prior to objective clinical impairment. However, the sensitivity of SCC reports in early AD may be biased by demographic factors. Here, we sought to investigate whether age, education, and sex influence the relationship between SCC and amyloid (Aβ) burden. METHODS: In this cross-sectional study, we examined 252 clinically normal (CN) individuals (57...
October 11, 2016: International Psychogeriatrics
Amado Rivero-Santana, Daniel Ferreira, Lilisbeth Perestelo-Pérez, Eric Westman, Lars-Olof Wahlund, Antonio Sarría, Pedro Serrano-Aguilar
BACKGROUND: Differential diagnosis in dementia is at present one of the main challenges both in clinical practice and research. Cerebrospinal fluid (CSF) biomarkers are included in the current diagnostic criteria of Alzheimer's disease (AD) but their clinical utility is still unclear. OBJECTIVE: We performed a systematic review of studies analyzing the diagnostic performance of CSF Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) in the discrimination between AD and frontotemporal lobar degeneration (FTLD) dementias...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Annika Öhrfelt, Ann Brinkmalm, Julien Dumurgier, Gunnar Brinkmalm, Oskar Hansson, Henrik Zetterberg, Elodie Bouaziz-Amar, Jacques Hugon, Claire Paquet, Kaj Blennow
BACKGROUND: Synaptic degeneration is a central pathogenic event in Alzheimer's disease that occurs early during the course of disease and correlates with cognitive symptoms. The pre-synaptic vesicle protein synaptotagmin-1 appears to be essential for the maintenance of an intact synaptic transmission and cognitive function. Synaptotagmin-1 in cerebrospinal fluid is a candidate Alzheimer biomarker for synaptic dysfunction that also may correlate with cognitive decline. METHODS: In this study, a novel mass spectrometry-based assay for measurement of cerebrospinal fluid synaptotagmin-1 was developed, and was evaluated in two independent sample sets of patients and controls...
October 3, 2016: Alzheimer's Research & Therapy
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