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Cognitive impairment biomarkers

Anders Wallin, Gustavo C Román, Margaret Esiri, Petronella Kettunen, Johan Svensson, George P Paraskevas, Elisabeth Kapaki
Subcortical small-vessel disease (SSVD) is a disorder well characterized from the clinical, imaging, and neuropathological viewpoints. SSVD is considered the most prevalent ischemic brain disorder, increasing in frequency with age. Vascular risk factors include hypertension, diabetes, hyperlipidemia, elevated homocysteine, and obstructive sleep apnea. Ischemic white matter lesions are the hallmark of SSVD; other pathological lesions include arteriolosclerosis, dilatation of perivascular spaces, venous collagenosis, cerebral amyloid angiopathy, microbleeds, microinfarcts, lacunes, and large infarcts...
2018: Journal of Alzheimer's Disease: JAD
José Luis Molinuevo, Carolina Minguillon, Lorena Rami, Juan Domingo Gispert
In the last decades, progress in neuroimaging techniques and cerebrospinal fluid assays has enabled the characterization of several Alzheimer's disease (AD) biomarkers. This knowledge has shifted the conceptualization of AD from a clinical-pathological construct, where its diagnosis required the presence of dementia with distinct pathologic features, toward a clinical-biological one that recognizes AD as a pathological continuum with a clinical picture that ranges from normal cognition to a dementia stage. Specifically, AD is now divided into three stages: preclinical (abnormal biomarkers and no or only subtle cognitive impairment), mild cognitive impairment or prodromal AD (abnormal pathophysiological biomarkers and episodic memory impairment), and dementia (abnormal biomarkers and clear cognitive and functional impairment)...
2018: Journal of Alzheimer's Disease: JAD
Lucilla Parnetti, Paolo Eusebi
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting around 35 million people worldwide. Cerebrospinal fluid (CSF) biomarkers entered the diagnostic criteria as support for early diagnosis. The classical biochemical signature of AD includes total tau (T-tau), phosphorylated tau (P-tau), and the 42 amino acid peptide (Aβ42) of amyloid-β. Recent observations suggest that the use of CSF Aβ42:Aβ40 ratio rather than CSF Aβ42 alone could contribute to reduce inter-laboratory variation in Aβ values and increasing diagnostic performance of the CSF AD biomarkers in routine practice...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Isabel Santana, Inês Baldeiras, Beatriz Santiago, Diana Duro, Sandra Freitas, Miguel Tábuas Pereira, Maria Rosário Almeida, Catarina Resende Oliveira
The amyloid cascade hypothesis proposes amyloid-β (Aβ) as the earliest and key pathological hallmark of Alzheimer's disease (AD), but this mandatory "amyloid-first pathway" has been contested. Longitudinal studies of mild cognitive impairment (MCI) patients represent an opportunity to investigate the intensity of underlying biological processes (amyloidosis versus neurodegeneration) and their relevance for progression to AD. We re-examined our cohort of amnestic MCI, grouped according to cerebrospinal fluid (CSF) biomarkers, aiming at establishing their prognostic value for Alzheimer-type dementia and testing the hypothetical model of biomarkers sequence, based on the amyloid cascade...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Jeffrey Cummings, Aaron Ritter, Kate Zhong
Alzheimer's disease (AD) has no currently approved disease-modifying therapies (DMTs), and treatments to prevent, delay the onset, or slow the progression are urgently needed. A delay of 5 years if available by 2025 would decrease the total number of patients with AD by 50% in 2050. To meet the definition of DMT, an agent must produce an enduring change in the course of AD; clinical trials of DMTs have the goal of demonstrating this effect. AD drug discovery entails target identification followed by high throughput screening and lead optimization of drug-like compounds...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Kichang Kwak, Hyuk Jin Yun, Gilsoon Park, Jong-Min Lee
BACKGROUND: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are age-related neurodegenerative diseases characterized by progressive loss of memory and irreversible cognitive functions. The hippocampus, a brain area critical for learning and memory processes, is especially susceptible to damage at early stages of AD. OBJECTIVE: We aimed to develop prediction model using a multi-modality sparse representation approach. METHODS: We proposed a sparse representation approach to the hippocampus using structural T1-weighted magnetic resonance imaging (MRI) and 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) to distinguish AD/MCI from healthy control subjects (HCs)...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Nicholas I Bradfield, Kathryn A Ellis, Greg Savage, Paul Maruff, Samantha Burnham, David Darby, Nicola T Lautenschlager, Ralph N Martins, Colin L Masters, Stephanie R Rainey-Smith, Joanne Robertson, Christopher Rowe, Michael Woodward, David Ames
BACKGROUND: Given the long preclinical disease course of Alzheimer disease (AD) pathology, novel treatments may be more efficacious if administered before the emergence of dementia. Thus, accurate prediction of who will develop AD dementia is of key importance in selecting individuals for trials of treatment and may become crucial for future selection of patients for therapy. METHODS: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 901 individuals who did not have dementia were recruited...
March 20, 2018: Alzheimer Disease and Associated Disorders
Geor Bakker, Claudia Vingerhoets, Daphne Boucherie, Matthan Caan, Oswald Bloemen, Jos Eersels, Jan Booij, Thérèse van Amelsvoort
Background: It is still unclear which underlying mechanisms are involved in cognitive deficits of psychotic disorders. Pro-cognitive effects of muscarinic M1 receptor agonists suggest alterations in M1 receptor functioning may modulate these symptoms. Post mortem studies in patients with schizophrenia have shown significantly reduced M1 receptor expression rates in the dorsolateral prefrontal cortex (DLPFC) compared to controls. To date no in-vivo examinations of M1 receptor binding in relation to cognitive impairments have been done...
2018: NeuroImage: Clinical
Joanne Gourgouvelis, Paul Yielder, Sandra T Clarke, Hushyar Behbahani, Bernadette Ann Murphy
Objective: The aim of this study is to investigate the effects of exercise as an add-on therapy with antidepressant medication and cognitive behavioral group therapy (CBGT) on treatment outcomes in low-active major depressive disorder (MDD) patients. We also explored whether exercise reduces the residual symptoms of depression, notably cognitive impairment and poor sleep quality, and aimed to identify putative biochemical markers related to treatment response. Methods: Sixteen low-active MDD patients were recruited from a mental health day treatment program at a local hospital...
2018: Frontiers in Psychiatry
Karem H Alzoubi, Omar F Khabour, Mohammad Ahmad
Posttraumatic stress disorder (PTSD) is a disabling prevalent and difficult-to-treat psychiatric disorder, which can develop after the exposure to severe traumatic events such as those occurring during wars and natural disasters. Pentoxifylline (PTX) is a potent antioxidant, which has an important role in prevention of cognitive dysfunctions. In the present study, the effect of PTX on memory impairment induced by PTSD was investigated using the rat animal model. PTSD-like behavior was induced in animals using a single-prolonged stress (SPS) rat model of PTSD (2 h restrain, 20 min forced swimming, 15 min rest, 1-2 min diethyl ether exposure)...
March 17, 2018: Brain Research Bulletin
Inês Baldeiras, Isabel Santana, Maria João Leitão, Helena Gens, Rui Pascoal, Miguel Tábuas-Pereira, José Beato-Coelho, Diana Duro, Maria Rosário Almeida, Catarina Resende Oliveira
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aβ42/40 ratio would improve MCI categorization and more accurately predict progression to AD...
March 20, 2018: Alzheimer's Research & Therapy
Dona M P Jayakody, Peter L Friedland, Ralph N Martins, Hamid R Sohrabi
Age-related hearing loss (ARHL), presbycusis, is a chronic health condition that affects approximately one-third of the world's population. The peripheral and central hearing alterations associated with age-related hearing loss have a profound impact on perception of verbal and non-verbal auditory stimuli. The high prevalence of hearing loss in the older adults corresponds to the increased frequency of dementia in this population. Therefore, researchers have focused their attention on age-related central effects that occur independent of the peripheral hearing loss as well as central effects of peripheral hearing loss and its association with cognitive decline and dementia...
2018: Frontiers in Neuroscience
Ellen Grober, Amy E Veroff, Richard B Lipton
Introduction: Free and Cued Selective Reminding Test (FCSRT) performance identifies patients with preclinical disease at elevated risk for developing Alzheimer's dementia, predicting diagnosis better than other memory tests. Methods: Based on literature mapping FCSRT performance to clinical outcomes and biological markers, and on longitudinal preclinical data from the Baltimore Longitudinal Study of Aging, we developed the Stages of Objective Memory Impairment (SOMI) model...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Mai Ishimiya, Hiroyuki Nakamura, Yutaka Kobayashi, Moeko Noguchi-Shinohara, Chiemi Abe, Chiaki Dohmoto, Yoshihisa Ikeda, Kahori Tokuno, Kazuhiro Ooi, Masami Yokokawa, Kazuo Iwasa, Kiyonobu Komai, Shuichi Kawashiri, Masahito Yamada
Although several studies have demonstrated a potential correlation of dietary patterns with cognitive function, the relationship between tooth loss and dietary patterns and cognitive function have not been identified. In this cross-sectional study, we used a reduced rank regression (RRR) analysis, a technique used previously to observe dietary patterns based on the intakes of nutrients or levels of biomarkers associated with the condition of interest, to identify tooth loss-related dietary patterns and investigate the associations of such patterns with cognitive impairment in 334 community-dwelling Japanese subjects aged ≥ 60 years...
2018: PloS One
Shinji Ouma, Midori Suenaga, Funda F Bölükbaşı Hatip, Izzettin Hatip-Al-Khatib, Yoshio Tsuboi, Yoichi Matsunaga
Objectives: To determine the relevance of Mini-Mental State Examination (MMSE), serum 25-hydroxyvitamin D (25(OH)D3), and 1,25(OH)2D3 concentrations to mild cognitive impairment (MCI) and various stages of Alzheimer's disease (AD). Materials and Methods: The study included 230 participants (>74 years) allocated to three main groups: 1-healthy subjects (HS, n  = 61), 2-patients with MCI ( n  = 61), and 3- patients with Alzheimer's disease (AD) subdivided into three stages: mild ( n  = 41), moderate ( n  = 35), and severe AD ( n  = 32)...
March 2018: Brain and Behavior
Hugo Botha, William G Mantyh, Melissa E Murray, David S Knopman, Scott A Przybelski, Heather J Wiste, Jonathan Graff-Radford, Keith A Josephs, Christopher G Schwarz, Walter K Kremers, Bradley F Boeve, Ronald C Petersen, Mary M Machulda, Joseph E Parisi, Dennis W Dickson, Val Lowe, Clifford R Jack, David T Jones
Predicting underlying pathology based on clinical presentation has historically proven difficult, especially in older cohorts. Age-related hippocampal sclerosis may account for a significant proportion of elderly participants with amnestic dementia. Advances in molecular neuroimaging have allowed for detailed biomarker-based phenotyping, but in the absence of antemortem markers of hippocampal sclerosis, cases of mixed pathology remain problematic. We evaluated the utility of 18F-FDG-PET to differentiate flortaucipir tau PET negative from flortaucipir positive amnestic mild cognitive impairment and dementia and used an autopsy confirmed cohort to test the hypothesis that hippocampal sclerosis might account for the observed pattern...
March 12, 2018: Brain: a Journal of Neurology
Bei-Bei Wu, Ye Ma, Lei Xie, Jin-Zhuang Huang, Zong-Bo Sun, Zhi-Duo Hou, Rui-Wei Guo, Zhi-Rong Lin, Shou-Xing Duan, Shan-Shan Zhao, Yao-Xie, Dan-Miao Sun, Chun-Min Zhu, Shu-Hua Ma
BACKGROUND: Systemic lupus erythematosus (SLE) is associated with cognitive deficit but the exact neural mechanisms remain unclear. PURPOSE: To explore sequential brain activities using functional magnetic resonance imaging (fMRI) during the performance of a decision-making task, and to determine whether serum or clinical markers can reflect the involvement of the brain in SLE. SUBJECTS: Sixteen female SLE patients without overt clinical neuropsychiatric symptoms and 16 healthy controls were included...
March 14, 2018: Journal of Magnetic Resonance Imaging: JMRI
Linqiong Sang, Lin Chen, Li Wang, Jingna Zhang, Ye Zhang, Pengyue Li, Chuanming Li, Mingguo Qiu
Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan...
2018: Frontiers in Neurology
Dong-Dong Shi, Celia M Dong, Leon C Ho, C T W Lam, Xi-Dan Zhou, Ed X Wu, Zhong-Jun Zhou, Xiao-Min Wang, Zhang-Jin Zhang
Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment...
March 10, 2018: Neurobiology of Disease
Gwendolien Vanderschaeghe, Kris Dierickx, Rik Vandenberghe
BACKGROUND: Today, many healthcare or dementia organizations, clinicians, and companies emphasize the importance of detection of Alzheimer's disease in an early phase. This idea has gained considerable momentum due to the development of biomarkers, the recent FDA and EMA approval of three amyloid tracers, and the failure of a number of recent therapeutic trials conducted in the early dementia phase. On the one hand, an early etiological diagnosis can lead to early and more efficacious intervention...
March 12, 2018: Journal of Bioethical Inquiry
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