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https://www.readbyqxmd.com/read/29022655/anosognosia-is-an-independent-predictor-of-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease-and-is-associated-with-reduced-brain-metabolism
#1
Philip Gerretsen, Jun Ku Chung, Parita Shah, Eric Plitman, Yusuke Iwata, Fernando Caravaggio, Shinichiro Nakajima, Bruce G Pollock, Ariel Graff-Guerrero
OBJECTIVE: Anosognosia, or impaired illness awareness, is a common feature of Alzheimer's disease (AD) and less so of mild cognitive impairment (MCI). Importantly, anosognosia negatively influences clinical outcomes for patients and their caregivers and may predict the conversion from MCI to AD. This study aimed to examine (1) the relationship between brain glucose metabolism as measured by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and anosognosia in patients with MCI and AD and (2) the predictive utility of anosognosia in patients with MCI for later conversion to AD, even when controlling for other factors, including gender, education, apolipoprotein E ε4 carrier status, dementia severity, and cognitive dysfunction...
October 10, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29018162/clinical-utility-of-amyloid-pet-imaging-with-18-f-florbetapir-a-retrospective-study-of-100-patients
#2
Christopher James Carswell, Zarni Win, Kirsty Muckle, Angus Kennedy, Adam Waldman, Gemma Dawe, Tara D Barwick, Sameer Khan, Paresh A Malhotra, Richard J Perry
BACKGROUND AND OBJECTIVE: Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer's disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the 'real-world' arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic...
October 10, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28991728/screening-for-cognitive-impairment-by-model-assisted-cerebral-blood-flow-estimation
#3
Toni Lassila, Luigi Yuri Di Marco, Micaela Mitolo, Vincenzo Iaia, Giorgio Levedianos, Annalena Venneri, Alejandro F Frangi
OBJECTIVE: Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disease; a major health concern in the ageing population with an estimated prevalence of 46 million dementia cases worldwide. Early diagnosis is therefore crucial so mitigating treatments can be initiated at an early stage. Cerebral hypoperfusion has been linked with blood-brain barrier dysfunction in the early stages of AD, and screening for chronic cerebral hypoperfusion in individuals has been proposed for improving the early diagnosis of AD...
October 5, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28990131/diagnosis-and-management-of-cognitive-and-behavioral-changes-in-dementia-with-lewy-bodies
#4
REVIEW
Babak Tousi
Proper diagnosis of dementia with Lewy bodies (DLB) in clinical practice remains suboptimal as many cases are misdiagnosed, usually as Alzheimer disease (AD) or Parkinson's disease (PD) and, in rare cases, psychosis. Therefore, it is important for patients with dementia to be thoroughly evaluated by a specialist who is familiar with current diagnostic tests and treatment options. New diagnostic criteria from the Dementia with Lewy Bodies Consortium have been developed to increase diagnostic sensitivity for DLB (Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium; McKeith et al...
October 9, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28985720/effects-of-homocysteine-on-white-matter-diffusion-parameters-in-alzheimer-s-disease
#5
Chen-Chang Lee, Shih-Wei Hsu, Chi-Wei Huang, Wen-Neng Chang, Sz-Fan Chen, Ming-Kung Wu, Chiung-Chih Chang, Lain-Chyr Hwang, Po-Chou Chen
BACKGROUND: The clinical features of Alzheimer's disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four diffusion tensor imaging parameters in the white matter of patients with early stage AD, examined their associations with homocysteine level, and tested the clinical significance of the diffusion tensor imaging parameters and homocysteine level in correlation analysis with cognitive test scores...
October 6, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28984594/alzheimer-s-disease-the-alternative-serotonergic-hypothesis-of-cognitive-decline
#6
Costa Vakalopoulos
The pathognomonic feature of Alzheimer's disease is a loss of declarative memory. This has generally been attributed to early involvement of medial temporal lobe structures with neurofibrillary tangles and loss of neurons in the entorhinal cortex. However, there has been a re-emerging emphasis on the causal role of brainstem monoaminergic nuclei as involvement of the cholinergic basal forebrain loses prominence. The rejection of this latter theory of cognitive decline is related to inconsistencies in time course and modest effects of treatment using cholinergic agents...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28984581/screening-for-alzheimer-s-disease-cognitive-impairment-in-self-referred-and%C3%A2-memory-clinic-referred-patients
#7
Bjørn-Eivind Kirsebom, Ragna Espenes, Knut Waterloo, Erik Hessen, Stein Harald Johnsen, Geir Bråthen, Dag Aarsland, Tormod Fladby
BACKGROUND: Cognitive assessment is essential in tracking disease progression in AD. Presently, cohorts including preclinical at-risk participants are recruited by different means, which may bias cognitive and clinical features. We compared recruitment strategies to levels of cognitive functioning. OBJECTIVE: We investigate recruitment source biases in self-referred and memory clinic-referred patient cohorts to reveal potential differences in cognitive performance and demographics among at-risk participants...
October 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28983098/tau-based-therapies-in-neurodegeneration-opportunities-and-challenges
#8
REVIEW
Chuanzhou Li, Jürgen Götz
Aggregates of the microtubule-associated protein tau are a defining feature of several neurodegenerative diseases that are collectively known as tauopathies, and constitute one of the hallmark lesions of Alzheimer disease (AD). Given the lack of efficacy to date of amyloid-β-targeted therapies for AD, interest is growing in tau as a potential alternative target. Several drug candidates, which are now in clinical trials, aim to reduce tau levels or to prevent the aggregation or pathological post-translation modifications of this protein...
October 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28978455/the-present-and-future-of-pharmacotherapy-of-alzheimer-s-disease-a-comprehensive-review
#9
REVIEW
Abhinav Anand, Albert Anosi Patience, Neha Sharma, Navneet Khurana
Alzheimer's disease (AD) is a generalized term used for the loss in memory and other intellectual abilities on levels serious enough to interfere with daily life. It accounts for 60-80% of dementia cases. The characteristic features include aggregation of Amyloid-Beta (Aβ) plaques and Tau Protein Tangles in the nervous tissue of brain. Another important aspect associated with development of AD is the decrease in levels of Acetylcholine (ACh) in brain. The conventional pharmacotherapy of AD employs the use of compounds that inhibit the enzyme acetylcholinesterase (e...
October 1, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28978335/attitudes-toward-clinical-trials-across-the-alzheimer-s-disease-spectrum
#10
Michelle M Nuño, Daniel L Gillen, Kulwant K Dosanjh, Jenny Brook, David Elashoff, John M Ringman, Joshua D Grill
BACKGROUND: Research has revealed that manifest Alzheimer's disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms...
October 4, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28974926/the-neuroanatomy-of-the-reticular-nucleus-locus-coeruleus-in-alzheimer-s-disease
#11
REVIEW
Filippo S Giorgi, Larisa Ryskalin, Riccardo Ruffoli, Francesca Biagioni, Fiona Limanaqi, Michela Ferrucci, Carla L Busceti, Ubaldo Bonuccelli, Francesco Fornai
Alzheimer's Disease (AD) features the accumulation of β-amyloid and Tau aggregates, which deposit as extracellular plaques and intracellular neurofibrillary tangles (NFTs), respectively. Neuronal Tau aggregates may appear early in life, in the absence of clinical symptoms. This occurs in the brainstem reticular formation and mostly within Locus Coeruleus (LC), which is consistently affected during AD. LC is the main source of forebrain norepinephrine (NE) and it modulates a variety of functions including sleep-waking cycle, alertness, synaptic plasticity, and memory...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28965295/comprehensive-and-methodical-diagnostic-and-management-approaches-to-rapidly-progressive-dementia
#12
REVIEW
Supriya Mahajan, Brian S Appleby
Purpose of review The sudden emergence of a change in cognitive abilities or behavior is an important symptom that warrants medical evaluation and may represent the early stages of a rapidly progressive dementia (RPD). To correctly ascertain the cause of RPD in a given patient, the clinician must be methodical and knowledgeable about the range of potential causes and must move forward with supportive treatment, and in some cases empiric treatment, based on clinical features alone. Recent findings Significant advances in prion disease biomarkers, the molecular features of rapidly progressive Alzheimer's disease, and new detection of autoimmune limbic encephalitis disease entities have caused a shift in the diagnostic and treatment framework of RPD...
September 30, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28965171/targeting-of-disordered-proteins-by-small-molecules-in-neurodegenerative-diseases
#13
Francesca Longhena, PierFranco Spano, Arianna Bellucci
The formation of protein aggregates and inclusions in the brain and spinal cord is a common neuropathological feature of a number of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and many others. These are commonly referred as neurodegenerative proteinopathies or protein-misfolding diseases. The main characteristic of protein aggregates in these disorders is the fact that they are enriched in amyloid fibrils. Since protein aggregation is considered to play a central role for the onset of neurodegenerative proteinopathies, research is ongoing to develop strategies aimed at preventing or removing protein aggregation in the brain of affected patients...
October 1, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28963120/chronic-cerebral-hypoperfusion-a-key-mechanism-leading-to-vascular-cognitive-impairment-and-dementia-closing-the-translational-gap-between-rodent-models-and-human-vascular-cognitive-impairment-and-dementia
#14
REVIEW
Jessica Duncombe, Akihiro Kitamura, Yoshiki Hase, Masafumi Ihara, Raj N Kalaria, Karen Horsburgh
Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD)...
October 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28960544/possible-concurrence-of-tdp-43-tau-and-other-proteins-in-amyotrophic-lateral-sclerosis-frontotemporal-lobar-degeneration
#15
REVIEW
Takahiro Takeda
Transactivation response DNA-binding protein 43 kDa (TDP-43) has been regarded as a major component of ubiquitin-positive/tau-negative inclusions of motor neurons and the frontotemporal cortices in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Neurofibrillary tangles (NFT), an example of tau-positive inclusions, are biochemically and morphologically distinguished from TDP-43-positive inclusions, and are one of the pathological core features of Alzheimer disease (AD). Although ALS/FTLD and AD are distinct clinical entities, they can coexist in an individual patient...
September 27, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28959379/empowering-cortical-thickness-measures-in-clinical-diagnosis-of-alzheimer-s-disease-with-spherical-sparse-coding
#16
Jie Zhang, Yonghui Fan, Qingyang Li, Paul M Thompson, Jieping Ye, Yalin Wang
Cortical thickness estimation performed in vivo via magnetic resonance imaging (MRI) is an important technique for the diagnosis and understanding of the progression of Alzheimer's disease (AD). Directly using raw cortical thickness measures as features with Support Vector Machine (SVM) for clinical group classification only yields modest results since brain areas are not equally atrophied during AD progression. Therefore, feature reduction is generally required to retain only the most relevant features for the final classification...
April 2017: Proceedings of the IEEE International Symposium on Biomedical Imaging: from Nano to Macro
https://www.readbyqxmd.com/read/28956123/the-value-of-subtraction-mri-in-detection-of-amyloid-related-imaging-abnormalities-with-oedema-or-effusion-in-alzheimer-s-patients-an-interobserver-study
#17
Roland M Martens, Arianne Bechten, Silvia Ingala, Ronald A van Schijndel, Vania B Machado, Marcus C de Jong, Esther Sanchez, Derk Purcell, Michael H Arrighi, Robert H Brashear, Mike P Wattjes, Frederik Barkhof
BACKGROUND: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases...
September 27, 2017: European Radiology
https://www.readbyqxmd.com/read/28955143/new-drug-research-and-development-for-alzheimer-s-pathology-present-and-prospect
#18
Tao Wang
Cholinesterase inhibitors and N-methyl-D-aspartic receptor antagonists are currently the main treatments for Alzheimer's disease (AD), targeting the clinical symptoms of AD. β-amyloid (Aβ) deposition and the highly-phosphorylated Tau protein-induced neurofibrillary tangles are some of the common pathological features of AD. In the past 20 years, many new drugs that focus on the pathogenesis of Alzheimer's disease have been assessed in clinical trials. Drugs such as β-amyloid monoclonal antibody and gamma-secretase inhibitor target the Aβ pathological pathway...
August 25, 2017: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28947125/statistical-modeling-of-huntington-disease-onset
#19
Tanya P Garcia, Karen Marder, Yuanjia Wang
Huntington disease (HD) is caused by a CAG trinucleotide expansion in the huntingtin gene. We now have the power to predict age-at-onset from subject-specific features like motor and neuroimaging measures. In clinical trials, properly modeling onset age is important, because it improves power calculations and directs clinicians to recruit subjects with certain features. The history of modeling onset, from simple linear and logistic regression to advanced survival models, is discussed. We highlight their advantages and disadvantages, emphasizing the methodological challenges when genetic mutation status is unavailable...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28942688/proteomic-studies-of-cerebrospinal-fluid-biomarkers-of-alzheimer-s-disease-an-update
#20
Erik Portelius, Gunnar Brinkmalm, Josef Pannee, Henrik Zetterberg, Kaj Blennow, Rahil Dahlén, Ann Brinkmalm, Johan Gobom
Alzheimer's disease (AD) is a neurodegenerative disease affecting the brain. Today there are three cerebrospinal fluid (CSF) biomarkers, amyloid-β consisting of 42 amino acids (Aβ42), total-tau (t-tau) and phosphorylated-tau (p-tau), which combined have sensitivity and specificity figures around 80%. However, pathological studies have shown that comorbidity is a common feature in AD and that the three currently used CSF biomarkers do not optimally reflect the activity of the disease process. Thus, additional markers are needed...
October 3, 2017: Expert Review of Proteomics
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