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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/27931251/conflicting-cerebrospinal-fluid-biomarkers-and-progression-to-dementia-due-to-alzheimer-s-disease
#1
Panagiotis Alexopoulos, Lukas Werle, Jennifer Roesler, Nathalie Thierjung, Lena Sophie Gleixner, Igor Yakushev, Nikolaos Laskaris, Stefan Wagenpfeil, Philippos Gourzis, Alexander Kurz, Robert Perneczky
BACKGROUND: According to new diagnostic guidelines for Alzheimer's disease (AD), biomarkers enable estimation of the individual likelihood of underlying AD pathophysiology and the associated risk of progression to AD dementia for patients with mild cognitive impairment (MCI). Nonetheless, how conflicting biomarker constellations affect the progression risk is still elusive. The present study explored the impact of different cerebrospinal fluid (CSF) biomarker constellations on the progression risk of MCI patients...
December 9, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27931245/brain-activation-in-frontotemporal-and-alzheimer-s-dementia-a-functional-near-infrared-spectroscopy-study
#2
Florian G Metzger, Betti Schopp, Florian B Haeussinger, Katja Dehnen, Matthis Synofzik, Andreas J Fallgatter, Ann-Christine Ehlis
BACKGROUND: Frontotemporal dementia is an increasingly studied disease, the underlying functional impairments on a neurobiological level of which have not been fully understood. Patients with the behavioral-subtype frontotemporal dementia (bvFTD) are particularly challenging for clinical measurements such as functional imaging due to their behavioral symptoms. Here, an alternative imaging method, functional near-infrared spectroscopy (fNIRS), is introduced to measure task-related cortical brain activation based on blood oxygenation...
December 8, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27915998/an-update-on-semantic-dementia-genetics-imaging-and-pathology
#3
REVIEW
Ramon Landin-Romero, Rachel Tan, John R Hodges, Fiona Kumfor
Progressive and relatively circumscribed loss of semantic knowledge, referred to as semantic dementia (SD) which falls under the broader umbrella of frontotemporal dementia, was officially identified as a clinical syndrome less than 50 years ago. Here, we review recent neuroimaging, pathological, and genetic research in SD. From a neuroimaging perspective, SD is characterised by hallmark asymmetrical atrophy of the anterior temporal pole and anterior fusiform gyrus, which is usually left lateralised. Functional magnetic resonance imaging (fMRI) studies have revealed widespread changes in connectivity, implicating the anterior temporal regions in semantic deficits in SD...
December 5, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27903289/changes-in-cerebral-glucose-metabolism-after-3%C3%A2-weeks-of-noninvasive-electrical-stimulation-of-mild-cognitive-impairment-patients
#4
Kyongsik Yun, In-Uk Song, Yong-An Chung
BACKGROUND: Mild cognitive impairment (MCI) is a syndrome that disrupts an individual's cognitive function but preserves activities of daily living. MCI is thought to be a prodromal stage of dementia, which disrupts patients' daily lives and causes severe cognitive dysfunction. Although extensive clinical trials have attempted to slow or stop the MCI to dementia conversion, the results have been largely unsuccessful. The purpose of this study was to determine whether noninvasive electrical stimulation of MCI changes glucose metabolism...
December 1, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27884212/angiotensin-converting-enzyme-2-is-reduced-in-alzheimer-s-disease-in-association-with-increasing-amyloid-%C3%AE-and-tau-pathology
#5
Patrick Gavin Kehoe, Steffenny Wong, Noura Al Mulhim, Laura Elyse Palmer, J Scott Miners
BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer's disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1-7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity...
November 25, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27866472/outcomes-measures-in-a-decade-of-dementia-and-mild-cognitive-impairment-trials
#6
Jennifer Kirsty Harrison, Anna H Noel-Storr, Nele Demeyere, Emma L Reynish, Terry J Quinn
BACKGROUND: In a research study, to give a comprehensive evaluation of the impact of interventions, the outcome measures should reflect the lived experience of the condition. In dementia studies, this necessitates the use of outcome measures which capture the range of disease effects, not limited to cognitive functioning. In particular, assessing the functional impact of cognitive impairment is recommended by regulatory authorities, but there is no consensus on the optimal approach for outcome assessment in dementia research...
November 21, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27846868/effect-of-concomitant-use-of-memantine-on-mortality-and-efficacy-outcomes-of-galantamine-treated-patients-with-alzheimer-s-disease-post-hoc-analysis-of-a-randomized-placebo-controlled-study
#7
Klaus Hager, Alan S Baseman, Jeffrey S Nye, H Robert Brashear, John Han, Mary Sano, Bonnie Davis, Henry M Richards
BACKGROUND: A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer's disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome. METHODS: Randomized patients (N = 2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints...
November 15, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27832826/psychological-behavioral-and-social-effects-of-disclosing-alzheimer-s-disease-biomarkers-to-research-participants-a-systematic-review
#8
S A S A Bemelmans, K Tromp, E M Bunnik, R J Milne, S Badger, C Brayne, M H Schermer, E Richard
BACKGROUND: Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants...
November 10, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27784332/using-the-affiliate-stigma-scale-with-caregivers-of-people-with-dementia-psychometric-evaluation
#9
Chih-Cheng Chang, Jian-An Su, Chung-Ying Lin
BACKGROUND: In this study, we examined the psychometric properties of the Affiliate Stigma Scale to measure affiliate stigma for caregivers of family members with dementia, a topic scantily covered in the literature. METHODS: Two hundred seventy-one caregivers were recruited. Each completed the Affiliate Stigma Scale, Caregiver Burden Inventory, Taiwanese Depression Questionnaire, Beck Anxiety Inventory, and 28-item World Health Organization Quality of Life questionnaire...
October 26, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27756421/abt-126-monotherapy-in-mild-to-moderate-alzheimer-s-dementia-randomized-double-blind-placebo-and-active-controlled-adaptive-trial-and-open-label-extension
#10
Laura M Gault, Robert A Lenz, Craig W Ritchie, Andreas Meier, Ahmed A Othman, Qi Tang, Scott Berry, Yili Pritchett, Weining Z Robieson
BACKGROUND: Results from a phase 2a study indicated that treatment with the novel α7 nicotinic acetylcholine receptor agonist ABT-126 25 mg once daily (QD) was associated with a trend for improvement in cognition in subjects with mild-to-moderate Alzheimer's dementia (AD). A phase 2b program was designed to evaluate a broader dose range of ABT-126 as monotherapy in subjects with mild-to-moderate AD. The program consisted of a double-blind, placebo and active controlled study of ABT-126 (dose range 25-75 mg) and an open-label extension study (75 mg)...
October 18, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27756387/identifying-biomarkers-of-dementia-prevalent-among-amnestic-mild-cognitively-impaired-ethnic-female-patients
#11
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
https://www.readbyqxmd.com/read/27724983/prospective-longitudinal-course-of-cognition-in-older-subjects-with-mild-parkinsonian-signs
#12
Stefanie Lerche, Kathrin Brockmann, Andrea Pilotto, Isabel Wurster, Ulrike Sünkel, Markus A Hobert, Anna-Katharina von Thaler, Claudia Schulte, Erik Stoops, Hugo Vanderstichele, Victor Herbst, Britta Brix, Gerhard W Eschweiler, Florian G Metzger, Walter Maetzler, Daniela Berg
BACKGROUND: Mild parkinsonian signs (MPS) are common in older people and are associated with an increased risk of different neurodegenerative diseases. This study prospectively evaluates the longitudinal course of cognitive performance in older individuals with MPS. METHODS: From the TREND study, 480 individuals neurologically healthy at baseline, aged between 50 and 80 years, with complete follow-up data for three assessments within a mean of 43.8 months, were included in this analysis...
October 10, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27716408/the-pre-synaptic-vesicle-protein-synaptotagmin-is-a-novel-biomarker-for-alzheimer-s-disease
#13
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
https://www.readbyqxmd.com/read/27683159/regional-tau-deposition-measured-by-18-f-thk5317-positron-emission-tomography-is-associated-to-cognition-via-glucose-metabolism-in-alzheimer-s-disease
#14
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
https://www.readbyqxmd.com/read/27646601/drug-development-in-alzheimer-s-disease-the-path-to-2025
#15
REVIEW
Jeffrey Cummings, Paul S Aisen, Bruno DuBois, Lutz Frölich, Clifford R Jack, Roy W Jones, John C Morris, Joel Raskin, Sherie A Dowsett, Philip Scheltens
The global impact of Alzheimer's disease (AD) continues to increase, and focused efforts are needed to address this immense public health challenge. National leaders have set a goal to prevent or effectively treat AD by 2025. In this paper, we discuss the path to 2025, and what is feasible in this time frame given the realities and challenges of AD drug development, with a focus on disease-modifying therapies (DMTs). Under the current conditions, only drugs currently in late Phase 1 or later will have a chance of being approved by 2025...
September 20, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27520290/older-patients-are-still-under-represented-in-clinical-trials-of-alzheimer-s-disease
#16
Rita Banzi, Paolo Camaioni, Mauro Tettamanti, Vittorio Bertele', Ugo Lucca
BACKGROUND: The age gap between participants in trials and patients who could benefit from the drugs studied has been widely documented across different clinical areas. Patients with dementia included in clinical research are systematically younger than those in the general population. We examined the age gap between participants in recent clinical trials testing interventions for Alzheimer's disease and epidemiological data. METHODS: We systematically searched literature databases (MedLine, EMBASE, the Cochrane Library) and ClinicalTrials...
August 12, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27473839/exploring-anterograde-memory-a-volumetric-mri-study-in-patients-with-mild-cognitive-impairment
#17
N Philippi, V Noblet, E Duron, B Cretin, C Boully, I Wisniewski, M L Seux, C Martin-Hunyadi, E Chaussade, C Demuynck, S Kremer, S Lehéricy, D Gounot, J P Armspach, O Hanon, F Blanc
BACKGROUND: The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample-48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer's disease, in which pathological changes typically start in this region. METHODS: We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study...
July 30, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27473681/recent-global-trends-in-the-prevalence-and-incidence-of-dementia-and-survival-with-dementia
#18
Martin Prince, Gemma-Claire Ali, Maëlenn Guerchet, A Matthew Prina, Emiliano Albanese, Yu-Tzu Wu
BACKGROUND: Current projections of the scale of the coming dementia epidemic assume that the age- and sex-specific prevalence of dementia will not vary over time, and that population ageing alone (increasing the number of older people at risk) drives the projected increases. The basis for this assumption is doubtful, and secular trends (that is, gradual decreases or increases in prevalence over long-term periods) are perfectly plausible. METHODS: We carried out a systematic review of studies of trends in prevalence, incidence and mortality for people with dementia, conducted since 1980...
July 30, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27389402/targeted-delivery-of-nerve-growth-factor-to-the-cholinergic-basal-forebrain-of-alzheimer-s-disease-patients-application-of-a-second-generation-encapsulated-cell-biodelivery-device
#19
Helga Eyjolfsdottir, Maria Eriksdotter, Bengt Linderoth, Göran Lind, Bengt Juliusson, Philip Kusk, Ove Almkvist, Niels Andreasen, Kaj Blennow, Daniel Ferreira, Eric Westman, Inger Nennesmo, Azadeh Karami, Taher Darreh-Shori, Ahmadul Kadir, Agneta Nordberg, Erik Sundström, Lars-Olof Wahlund, Anders Wall, Maria Wiberg, Bengt Winblad, Åke Seiger, Lars Wahlberg, Per Almqvist
BACKGROUND: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. METHODS: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration...
July 7, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27386850/retraction-note-efficacy-and-safety-of-atypical-antipsychotic-drug-treatment-for-dementia-a-systematic-review-and-meta-analysis
#20
Lin Tan, Lan Tan, Hui-Fu Wang, Jun Wang, Chen-Chen Tan, Meng-Shan Tan, Xiang-Fei Meng, Chong Wang, Jin-Tai Yu
No abstract text is available yet for this article.
July 7, 2016: Alzheimer's Research & Therapy
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