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Prodromal AD

Xue-Yuan Li, Wei-Wei Men, Hua Zhu, Jian-Feng Lei, Fu-Xing Zuo, Zhan-Jing Wang, Zhao-Hui Zhu, Xin-Jie Bao, Ren-Zhi Wang
Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using (18)F-labed fluorodeoxyglucose ((18)F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr)...
October 18, 2016: International Journal of Molecular Sciences
Zora Kikinis, Kang Ik K Cho, Ioana L Coman, Petya D Radoeva, Sylvain Bouix, Yingying Tang, Ryan Eckbo, Nikos Makris, Jun Soo Kwon, Marek Kubicki, Kevin M Antshel, Wanda Fremont, Martha E Shenton, Wendy R Kates
BACKGROUND: 22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30 % probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia. METHODS: Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/-2 years)...
October 11, 2016: Brain Imaging and Behavior
Wei Li, Tao Wang, Shifu Xiao
BACKGROUND: Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer's disease (AD), so identification of the related risk factors can be helpful. Although the association between type 2 diabetes mellitus (T2DM) and these modest changes in cognition is well established, whether T2DM will promote the transformation of MCI into AD is not a unified conclusion. OBJECTIVE: This study aims to explore the relationship between T2DM and MCI in the elderly population living in the community in Shanghai, People's Republic of China...
2016: Neuropsychiatric Disease and Treatment
Laure Saint-Aubert, Ove Almkvist, Konstantinos Chiotis, Rita Almeida, Anders Wall, Agneta Nordberg
BACKGROUND: The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification of regional tau deposition and offers the opportunity to monitor the progression of tau pathology along with cognitive impairment. In this study, we investigated the relationships of cerebral tau deposition ([(18)F]THK5317-PET) and metabolism ([(18)F]FDG-PET) with concomitant cognitive function in patients with probable Alzheimer's disease (AD). METHODS: Nine patients diagnosed with AD dementia and 11 with prodromal AD (mild cognitive impairment, amyloid-positive on [(11)C]PiB-PET) were included in this study...
September 29, 2016: Alzheimer's Research & Therapy
Whitney M Freeze, Heidi I L Jacobs, Ed H Gronenschild, Jacobus F A Jansen, Saartje Burgmans, Pauline Aalten, Lies Clerx, Stephanie J Vos, Mark A van Buchem, Frederik Barkhof, Wiesje M van der Flier, Marcel M Verbeek, Marcel Olde Rikkert, Walter H Backes, Frans R Verhey
Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence...
September 20, 2016: Journal of Alzheimer's Disease: JAD
Pashtun Shahim, Kaj Blennow, Per Johansson, Johan Svensson, Simone Lista, Harald Hampel, Leif Christer Andersson, Henrik Zetterberg
Stanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer's disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder, particularly Alzheimer's disease (AD), has not been investigated before. We measured STC-1 in cerebrospinal fluid (CSF) samples from a total of 163 individuals including AD, prodromal AD (pAD), mixed AD, stable mild cognitive impairment (sMCI), and diagnoses of other dementia than AD, as well as cognitively normal controls (CNC) enrolled at academic centers in France and Sweden...
September 19, 2016: Neuromolecular Medicine
Daniela Scarabino, Elisabetta Broggio, Giuseppe Gambina, Carlotta Maida, Maria Rosa Gaudio, Rosa Maria Corbo
Mild cognitive impairment (MCI) is the transition stage between the normal aging process and dementia itself. The most common clinical phenotype is amnestic MCI (aMCI) [subtypes: single domain (sMCI) and multiple domains (mMCI)], which is considered prodromal to Alzheimer's disease (AD). The APOE (apolipoprotein E) e4 allele is the most important genetic risk factor for AD, but its association with MCI onset and conversion to AD is controversial. In this follow-up study of 88 aMCI patients (68% sMCI and 32% mMCI at baseline), we examined APOE genotypes and plasma levels in relation to MCI development and progression based on their clinical/cognitive data obtained at baseline and follow-up assessment (mean follow-up time = 6...
September 8, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Kyung-Ok Lim, Tae Young Lee, Minah Kim, Myong-Wuk Chon, Je-Yeon Yun, Sung Nyun Kim, Jun Soo Kwon
AIM: A clinical high risk (CHR) for psychosis is regarded as the state of being at risk of developing psychosis. However, the rate of transition to psychosis among CHR subjects has been declining over time. We aimed to investigate the effects of the possible causes of the declining transition rate. METHODS: A total of 129 CHR subjects were divided into two groups according to the date of enrollment: the 2005-2009 group and the 2009-2013 group. Baseline demographic and clinical characteristics, including medication prescription, were compared...
September 7, 2016: Early Intervention in Psychiatry
Marat A Mukhamedyarov, Albert A Rizvanov, Eduard Z Yakupov, Andrey L Zefirov, Andrey P Kiyasov, Helton J Reis, Antônio L Teixeira, Luciene B Vieira, Luciana M Lima, Ilnur I Salafutdinov, Elena O Petukhova, Svetlana F Khaiboullina, Karen A Schlauch, Vincent C Lombardi, András Palotás
Alzheimer's disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-β plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging...
October 18, 2016: Journal of Alzheimer's Disease: JAD
Salvatore Mazzeo, Roberto Santangelo, Maria Paola Bernasconi, Giordano Cecchetti, Agnese Fiorino, Patrizia Pinto, Gabriella Passerini, Monica Falautano, Giancarlo Comi, Giuseppe Magnani
BACKGROUND: Correctly diagnosing Alzheimer's disease (AD) in prodromal phases would allow the adoption of experimental therapeutic strategies that could selectively interrupt the pathogenetic process before neuronal damage becomes irreversible. Therefore, great efforts have been aimed at finding early reliable disease markers. OBJECTIVE: The aim of this study was to identify a simple, cost effective, and reliable diagnostic algorithm to predict conversion from mild cognitive impairment (MCI) to AD...
October 18, 2016: Journal of Alzheimer's Disease: JAD
Jeff Sevigny, Ping Chiao, Thierry Bussière, Paul H Weinreb, Leslie Williams, Marcel Maier, Robert Dunstan, Stephen Salloway, Tianle Chen, Yan Ling, John O'Gorman, Fang Qian, Mahin Arastu, Mingwei Li, Sowmya Chollate, Melanie S Brennan, Omar Quintero-Monzon, Robert H Scannevin, H Moore Arnold, Thomas Engber, Kenneth Rhodes, James Ferrero, Yaming Hang, Alvydas Mikulskis, Jan Grimm, Christoph Hock, Roger M Nitsch, Alfred Sandrock
Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner...
August 31, 2016: Nature
So Yeon Jeon, Dahyun Yi, Min Soo Byun, Hyo Jung Choi, Hyun Jung Kim, Jun Ho Lee, Hyewon Baek, Young Min Choe, Younghwa Lee, Jong Inn Woo, Dong Young Lee
Although amnestic mild cognitive impairment (aMCI) with high cerebral deposition of amyloid-beta proteins (Aβ) could be classified as a prodromal state of Alzheimer's disease (AD) dementia, aMCI with the absence of or very little cerebral Aβ deposition is likely related to other pathophysiological processes. Thus, the present study aimed to investigate the differential patterns of regional cerebral glucose metabolism (rCMglu) according to the level of Aβ burden in the brains of patients with aMCI. This study included 25 patients with aMCI and 33 cognitively normal (CN) elderly individuals who underwent a comprehensive clinical examination, (11)C-labelled Pittsburgh Compound B (PiB) positron emission tomography (PET) scans, and (18)F-fluorodeoxyglucose (FDG) PET scans...
October 6, 2016: Neuroscience Letters
Louis De Beaumont, Sandra Pelleieux, Louise Lamarre-Théroux, Doris Dea, Judes Poirier
BACKGROUND: Genetic heterogeneity in amnestic mild cognitively impaired (aMCI) subjects could lead to variations in progression rates and response to cholinomimetic agents. Together with the apolipoprotein E4 (APOE-ɛ4) gene, butyrylcholinesterase (BCHE) has become recently one of the few Alzheimer's disease (AD) susceptibility genes with distinct pharmacogenomic properties. OBJECTIVE: To validate candidate genes (APOE/BCHE) which display associations with age of onset of AD and donepezil efficacy in aMCI subjects...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Eske Christiane Gertje, John Pluta, Sandhitsu Das, Lauren Mancuso, Dasha Kliot, Paul Yushkevich, David Wolk
BACKGROUND: Volumetry of medial temporal lobe (MTL) structures to diagnose Alzheimer's disease (AD) in its earliest symptomatic stage could be of great importance for interventions or disease modifying pharmacotherapy. OBJECTIVE: This study aimed to demonstrate the first application of an automatic segmentation method of MTL subregions in a clinical population. Automatic segmentation of magnetic resonance images (MRIs) in a research population has previously been shown to detect evidence of neurodegeneration in MTL subregions and to help discriminate AD and mild cognitive impairment (MCI) from a healthy comparison group...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Charisse Somers, Hanne Struyfs, Joery Goossens, Ellis Niemantsverdriet, Jill Luyckx, Naomi De Roeck, Ellen De Roeck, Bart De Vil, Patrick Cras, Jean-Jacques Martin, Peter-Paul De Deyn, Maria Bjerke, Sebastiaan Engelborghs
During the past ten years, over 5,000 cerebrospinal fluid (CSF) samples were analyzed at the Reference Center for Biological Markers of Dementia (BIODEM), UAntwerp, for core Alzheimer's disease (AD) CSF biomarkers: amyloid-β peptide of 42 amino acids (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P). CSF biomarker analyses were performed using single-analyte ELISA kits. In-house validated cutoff values were applied: Aβ1-42 <638.5 pg/mL, T-tau >296.5 pg/mL, P-tau181P >56...
August 10, 2016: Journal of Alzheimer's Disease: JAD
Laura Prieto Del Val, Jose L Cantero, Mercedes Atienza
Synaptic dysfunction, a key pathophysiological hallmark of Alzheimer's disease (AD), may account for abnormal memory-related EEG patterns in prodromal AD. Here, we investigate to what extent oscillatory EEG changes during memory encoding and/or retrieval enhance the accuracy of medial temporal lobe (MTL) atrophy in predicting conversion from amnestic mild cognitive impairment (aMCI) to AD. As expected, aMCI individuals that, within a 2-year follow-up period, developed dementia (N = 16) compared to healthy older (HO) (N = 26) and stable aMCI (N = 18) showed poorer associative memory, greater MTL atrophy, and lower capacity to recruit alpha oscillatory cortical networks...
2016: Scientific Reports
M S Unger, J Marschallinger, J Kaindl, C Höfling, S Rossner, Michael T Heneka, A Van der Linden, Ludwig Aigner
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the Western world and is characterized by a progressive loss of cognitive functions leading to dementia. One major histopathological hallmark of AD is the formation of amyloid-beta plaques, which is reproduced in numerous transgenic animal models overexpressing pathogenic forms of amyloid precursor protein (APP). In human AD and in transgenic amyloid plaque mouse models, several studies report altered rates of adult neurogenesis, i...
October 2016: Molecular Neurobiology
Paolo Maria Rossini, Riccardo Di Iorio, Giuseppe Granata, Francesca Miraglia, Fabrizio Vecchio
In a recent study, analyzing the modulation of γ-band oscillations, Naro and colleagues demonstrated that transcranial alternating current stimulation could drive the gamma rhythms in the human EEG in cognitive healthy elderly subjects but not in mild cognitive impairment (MCI) prodromal to Alzheimer's disease (AD) and in early AD patients. Therefore, this method is proposed to intercept early in the disease course those MCI subjects who are in a pre-symptomatic stage of an already established AD. This prediction index may help the clinician to adopt a better prevention/follow-up strategy...
July 14, 2016: Journal of Alzheimer's Disease: JAD
Samantha C Burnham, Christopher C Rowe, David Baker, Ashley I Bush, James D Doecke, Noel G Faux, Simon M Laws, Ralph N Martins, Paul Maruff, S Lance Macaulay, Stephanie Rainey-Smith, Greg Savage, David Ames, Colin L Masters, William Wilson, Victor L Villemagne
OBJECTIVE: We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying individuals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify individuals at risk of progression to Alzheimer disease (AD) within 54 months. METHODS: We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants with mild cognitive impairment (MCI) from the Australian Imaging, Biomarkers and Lifestyle Study who underwent clinical reclassification (blinded to biomarker findings) at 54-month follow-up...
September 13, 2016: Neurology
Cristina Sanfilippo, Orestes Forlenza, Henrik Zetterberg, Kaj Blennow
Synaptic dysfunction is linked to both major depressive disorder (MDD) and Alzheimer's disease (AD). Synapse protein concentrations in cerebrospinal fluid (CSF) may be useful biomarkers to monitor synaptic dysfunction and degeneration that lead to depressive symptoms and AD, respectively. CSF neurogranin (Ng), a post-synaptic protein, has emerged as a promising tool to measure synaptic dysfunction and/or loss in AD. The aim of this study was to test the specific hypothesis that CSF neurogranin (Ng) is able to differentiate AD from MDD and cognitively normal controls...
August 16, 2016: Journal of Neural Transmission
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