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Prodromal AD

Karolina Kauppi, Chun Chieh Fan, Linda K McEvoy, Dominic Holland, Chin Hong Tan, Chi-Hua Chen, Ole A Andreassen, Rahul S Desikan, Anders M Dale
Improved prediction of progression to Alzheimer's Disease (AD) among older individuals with mild cognitive impairment (MCI) is of high clinical and societal importance. We recently developed a polygenic hazard score (PHS) that predicted age of AD onset above and beyond APOE . Here, we used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to further explore the potential clinical utility of PHS for predicting AD development in older adults with MCI. We examined the predictive value of PHS alone and in combination with baseline structural magnetic resonance imaging (MRI) data on performance on the Mini-Mental State Exam (MMSE)...
2018: Frontiers in Neuroscience
Takeshi Iwatsubo, Atsushi Iwata, Kazushi Suzuki, Ryoko Ihara, Hiroyuki Arai, Kenji Ishii, Michio Senda, Kengo Ito, Takeshi Ikeuchi, Ryozo Kuwano, Hiroshi Matsuda, Chung-Kai Sun, Laurel A Beckett, Ronald C Petersen, Michael W Weiner, Paul S Aisen, Michael C Donohue
INTRODUCTION: We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America. METHODS: A total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography- or cerebrospinal fluid amyloid β(1-42)-positive LMCI and mild AD between J-ADNI and ADNI...
May 8, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Christian Benedict, Claudia A Grillo
Research in animals and humans has shown that type 2 diabetes and its prodromal state, insulin resistance, promote major pathological hallmarks of Alzheimer's disease (AD), such as the formation of amyloid plaques and neurofibrillary tangles (NFT). Worrisomely, dysregulated amyloid beta (Aβ) metabolism has also been shown to promote central nervous system insulin resistance; although the role of tau metabolism remains controversial. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted insulin signaling...
2018: Frontiers in Neuroscience
Soo Hyun Joo, Se Hee Yun, Dong Woo Kang, Chang Tae Hahn, Hyun Kook Lim, Chang Uk Lee
Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. The association of body mass index (BMI) and progression to Alzheimer's disease (AD) in MCI subjects according to age, sex, and cognitive intervention remains unknown. We investigated the relationship between BMI and the risk of progression to AD in subjects with MCI, as well as the effect of BMI on progression to AD depending on age, sex, cognitive intervention, and chronic diseases. Methods: Three hundred and eighty-eight MCI subjects were followed for 36...
2018: Frontiers in Psychiatry
Minesh Kapadia, M Firoz Mian, Bernadeta Michalski, Amber Azam, Donglai Ma, Patrick Salwierz, Adam Christopher, Elyse Rosa, Iva Zovkic, Paul Forsythe, Margaret Fahnestock, Boris Sakic
The triple-transgenic (3xTg-AD) mouse strain is a valuable model of Alzheimer's disease (AD) because it develops both amyloid-β (Aβ) and tau brain pathology. However, 1-year-old 3xTg-AD males no longer show plaques and tangles, yet early in life, they exhibit diverse signs of systemic autoimmunity. The current study aimed to address whether females, which exhibit more severe plaque/tangle pathology at 1 year of age, show similar autoimmune phenomena and if so, whether these immunological changes coincide with prodromal markers of AD pathology, markers of learning and memory formation and epigenetic markers of neurodegenerative disease...
April 25, 2018: Journal of Alzheimer's Disease: JAD
Javier Arbizu, Cristina Festari, Daniele Altomare, Zuzana Walker, Femke Bouwman, Jasmine Rivolta, Stefania Orini, Henryk Barthel, Federica Agosta, Alexander Drzezga, Peter Nestor, Marina Boccardi, Giovanni Battista Frisoni, Flavio Nobili
PURPOSE: We aim to report the quality of accuracy studies investigating the utility of [18 F]fluorodeoxyglucose (FDG)-PET in supporting the diagnosis of prodromal Alzheimer's Disease (AD), frontotemporal lobar degeneration (FTLD) and prodromal dementia with Lewy bodies (DLB) in mild cognitive impairment (MCI) subjects, and the corresponding recommendations made by a panel of experts. METHODS: Seven panellist, four from the European Association of Nuclear Medicine, and three from the European Academy of Neurology, produced recommendations taking into consideration the incremental value of FDG-PET, as added on clinical-neuropsychological examination, to ascertain the aetiology of MCI (AD, FTLD or DLB)...
April 27, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Biao Jie, Mingxia Liu, Dinggang Shen
Functional connectivity networks (FCNs) using resting-state functional magnetic resonance imaging (rs-fMRI) have been applied to the analysis and diagnosis of brain disease, such as Alzheimer's disease (AD) and its prodrome, i.e., mild cognitive impairment (MCI). Different from conventional studies focusing on static descriptions on functional connectivity (FC) between brain regions in rs-fMRI, recent studies have resorted to dynamic connectivity networks (DCNs) to characterize the dynamic changes of FC, since dynamic changes of FC may indicate changes in macroscopic neural activity patterns in cognitive and behavioral aspects...
April 4, 2018: Medical Image Analysis
Chiara Cerami, Alessandra Dodich, Sandro Iannaccone, Giuseppe Magnani, Roberto Santangelo, Luca Presotto, Alessandra Marcone, Luigi Gianolli, Stefano F Cappa, Daniela Perani
BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous syndrome resulting from Alzheimer's disease (AD) as well as to non-AD and non-neurodegenerative conditions. A subset of patients with amnestic MCI (aMCI) present with an unusually long-lasting course, a slow rate of clinical neuropsychological progression, and evidence of focal involvement of medial temporal lobe structures. In the present study, we explored positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a sample of subjects with aMCI with such clinical features in order to provide in vivo evidence to improve disease characterisation in this subgroup...
April 25, 2018: Alzheimer's Research & Therapy
Anuraag R Kansal, Ali Tafazzoli, K Jack Ishak, Stanmira Krotneva
Introduction: Several advances have been made in Alzheimer's Disease (AD) modeling, however, there remains a need for a simulator that represents the full scope of disease progression and can be used to study new disease-modifying treatments for early-stage and even prodromal AD. Methods: We developed AD Archimedes condition-event simulator, a patient-level simulator with a focus on simulating the effects of early interventions through changes in biomarkers of AD...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Ilijana Begcevic, Davor Brinc, Marshall Brown, Eduardo Martinez-Morillo, Oliver Goldhardt, Timo Grimmer, Viktor Magdolen, Ihor Batruch, Eleftherios P Diamandis
Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline. The main disease hallmarks include amyloid beta aggregates and neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF); the core biomarkers amyloid beta 1-42, total and phosphorylated tau protein levels are changed, relative to cognitively normal elderly. Still, there is a need for additional biomarkers which could identify disease more accurately and at an earlier stage, predict severity and be used in research settings...
April 20, 2018: Journal of Proteomics
Lijun Wang
Cerebrospinal fluid (CSF) Neurogranin has recently been proposed as a potential biomarker for cognitive decline and brain injury in Alzheimer's disease (AD). To test whether CSF Neurogranin levels are increased in AD and its association with cognitive decline, we examined 99 cognitively normal (CN) subjects, 171 patients with mild cognitive impairment (MCI), and 81 patients with AD in the cross-sectional study from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The results showed that CSF Neurogranin was increased in both AD and MCI compared with controls...
April 17, 2018: Aging Clinical and Experimental Research
Bardia Nouriziabari, Susmita Sarkar, Stephanie E Tanninen, Robert D Dayton, Ronald L Klein, Kaori Takehara-Nishiuchi
Trace eyeblink conditioning is a hippocampus-dependent associative learning paradigm which is impaired in patients with Alzheimer's disease (AD) and animal AD models. Learning in this paradigm accompanies changes in oscillatory activity in forebrain regions, some of which are loci of pathogenic changes in prodromal AD stages. These observations motivated us to examine how cortical event-related potentials (ERPs) during this paradigm are affected by two features of the asymptomatic, AD-related brain abnormality, entorhinal tau accumulation and mild cholinergic deficit...
April 11, 2018: Journal of Alzheimer's Disease: JAD
Patrick M Flanigan, Mitra A Khosravi, James B Leverenz, Babak Tousi
OBJECTIVE: Dementia with Lewy bodies (DLB) is frequently misdiagnosed for Alzheimer dementia (AD), especially in its earlier stages. We characterized color vision impairment (CVI) in patients with DLB versus patients with AD to determine its usefulness in improving accuracy of early diagnosis. METHODS: We retrospectively reviewed charts of patients with AD, DLB, and patients with mild cognitive impairment suspected to be in the prodromal phase of DLB (pro-DLB) or prodromal phase of AD (pro-AD)...
March 2018: Journal of Geriatric Psychiatry and Neurology
Abhai Kumar, Smita Singh, Ashish Verma, Vijay Nath Mishra
Mild cognitive impairment (MCI) is an intermediate stage of cognitive decline and dementia. The absence of specific diagnostic test for identification of MCI and AD. The current study aims to find proteomics based change in plasma proteins and diffusion tensor imaging (DTI) based white matter changes in MCI for early detection of prodromal Alzheimer's disease. Fifty cases of mild cognitive impairment and age matched control between (55-75 yrs) were screened on basis of Mini Mental State Examination (MMSE). Two dimensional gel electrophoresis and DTI imaging was performed in MCI and age matched control...
April 9, 2018: Neuroscience Letters
Andreas Nabers, Laura Perna, Julia Lange, Ute Mons, Jonas Schartner, Jörn Güldenhaupt, Kai-Uwe Saum, Shorena Janelidze, Bernd Holleczek, Dan Rujescu, Oskar Hansson, Klaus Gerwert, Hermann Brenner
Alzheimer's disease (AD) is currently incurable, but there is general agreement that a minimally invasive blood biomarker for screening in preclinical stages would be crucial for future therapy. Diagnostic tools for detection of AD are either invasive like cerebrospinal fluid (CSF) biomarkers or expensive such as positron emission tomography (PET) scanning. Here, we determine the secondary structure change of amyloid-β (Aβ) in human blood. This change used as blood amyloid biomarker indicates prodromal AD and correlates with CSF AD biomarkers and amyloid PET imaging in the cross-sectional BioFINDER cohort...
May 2018: EMBO Molecular Medicine
J Luo, H Weng, J C Morris, C Xiong
BACKGROUND: Clinical trials of investigational drugs for Alzheimer disease (AD) increasingly focus on the prodromal (symptomatic) stage of the illness and now its preclinical (asymptomatic) stage. Sensitive and specific cognitive and functional endpoints are needed to track subtle cognitive and functional changes in the early and preclinical stages to minimize sample sizes in these trials. OBJECTIVES: To identify informative items in a standard clinical assessment protocol and a psychometric battery that are predictive of onset of dementia symptom...
2018: Journal of Prevention of Alzheimer's Disease
Dongren Yao, Vince D Calhoun, Zening Fu, Yuhui Du, Jing Sui
Discriminating Alzheimer's disease (AD) from its prodromal form, mild cognitive impairment (MCI), is a significant clinical problem that may facilitate early diagnosis and intervention, in which a more challenging issue is to classify MCI subtypes, i.e., those who eventually convert to AD (cMCI) versus those who do not (MCI). To solve this difficult 4-way classification problem (AD, MCI, cMCI and healthy controls), a competition was hosted by Kaggle to invite the scientific community to apply their machine learning approaches on pre-processed sets of T1-weighted magnetic resonance images (MRI) data and the demographic information from the international Alzheimer's disease neuroimaging initiative (ADNI) database...
March 22, 2018: Journal of Neuroscience Methods
Shumita Roy, Allison Drake, Stephanie Snyder, Breana Cline, Anjum Khan, Tom Fuchs, Robert Zivadinov, Bianca Weinstock-Guttman, Kinga Szigeti, Ralph H B Benedict
BACKGROUND: Cognitive impairment can be seen in patients of all ages with multiple sclerosis (MS). However, there is limited research on neurocognitive disorder in older adults with MS and how to detect Alzheimer's disease (AD) or its prodromal stage, amnestic mild cognitive impairment (aMCI). Thus, the MS clinician is challenged to discriminate between signs of MS-related cognitive decline versus a secondary neurodegenerative process. OBJECTIVE: Compare cognition in older MS patients to patients with AD and aMCI...
March 13, 2018: Multiple Sclerosis and related Disorders
Kaj Blennow, Henrik Zetterberg
Following the development of the first methods to measure the core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers total-tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of amyloid-β (Aβ42), there has been an enormous expansion of this scientific research area. Today, it is generally acknowledged that these biochemical tests reflect several central pathophysiological features of AD and contribute diagnostically relevant information, also for prodromal AD. In this article in the 20th anniversary issue of the Journal of Alzheimer's Disease, we review the AD biomarkers, from early assay development to their entrance into diagnostic criteria...
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
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