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Alzheimer's Research & Therapy

Bryce Tan, Narayanaswamy Venketasubramanian, Henri Vrooman, Ching-Yu Cheng, Tien Yin Wong, Christopher Chen, Saima Hilal
BACKGROUND: Low haemoglobin is highly prevalent among the elderly and has been associated with dementia. However, the mechanisms underlying this association with cognitive dysfunction, either through cerebrovascular disease or neurodegeneration, remain poorly understood. We aimed to examine the association of decreased haemoglobin levels with markers of cerebral small vessel disease (CSVD), neurodegeneration and cognitive impairment in an elderly Asian population. METHODS: A total of 796 Chinese, Malay and Indian participants aged 60 years and older from the Epidemiology of Dementia in Singapore study were included in this study...
November 6, 2018: Alzheimer's Research & Therapy
Raquel Sánchez-Valle, Amanda Heslegrave, Martha S Foiani, Beatriz Bosch, Anna Antonell, Mircea Balasa, Albert Lladó, Henrik Zetterberg, Nick C Fox
BACKGROUND: Biomarkers that can track disease onset and progression in autosomal dominant Alzheimer's disease (ADAD) are needed. We investigate whether serum neurofilament light (NfL) concentration is associated with clinical and cerebrospinal fluid (CSF) markers in ADAD. We also evaluate serum NfL differences between clinical groups. METHODS: Serum NfL was measured cross-sectionally in 60 individuals from ADAD families using an ultrasensitive immunoassay on the Single molecule array (Simoa) platform and longitudinally in an exploratory study in a subset of six mutation carriers...
November 3, 2018: Alzheimer's Research & Therapy
Ruey Chen, Wu-Chien Chien, Ching-Chiu Kao, Chi-Hsiang Chung, Doresses Liu, Huei-Ling Chiu, Kuei-Ru Chou
BACKGROUND: Most previous studies on dementia and injuries have focused on a particular type of injury, and few studies have investigated overall injury in people with dementia. In this study, we investigated the risk factors and risk of overall injury, including the diagnosis, cause, and intentionality of injury, in people with and without dementia in Taiwan. METHODS: We collected relevant data between 2000 and 2013 from the National Health Insurance Research Database (NHIRD)...
October 30, 2018: Alzheimer's Research & Therapy
Mara Ten Kate, Silvia Ingala, Adam J Schwarz, Nick C Fox, Gaël Chételat, Bart N M van Berckel, Michael Ewers, Christopher Foley, Juan Domingo Gispert, Derek Hill, Michael C Irizarry, Adriaan A Lammertsma, José Luis Molinuevo, Craig Ritchie, Philip Scheltens, Mark E Schmidt, Pieter Jelle Visser, Adam Waldman, Joanna Wardlaw, Sven Haller, Frederik Barkhof
BACKGROUND: In Alzheimer's disease (AD), pathological changes may arise up to 20 years before the onset of dementia. This pre-dementia window provides a unique opportunity for secondary prevention. However, exposing non-demented subjects to putative therapies requires reliable biomarkers for subject selection, stratification, and monitoring of treatment. Neuroimaging allows the detection of early pathological changes, and longitudinal imaging can assess the effect of interventions on markers of molecular pathology and rates of neurodegeneration...
October 30, 2018: Alzheimer's Research & Therapy
Gloria Benson, Andrea Hildebrandt, Catharina Lange, Claudia Schwarz, Theresa Köbe, Werner Sommer, Agnes Flöel, Miranka Wirth
BACKGROUND: Cerebrovascular pathology, quantified by white matter lesions (WML), is known to affect cognition in aging, and is associated with an increased risk of dementia. The present study aimed to investigate whether higher functional connectivity in cognitive control networks mitigates the detrimental effect of WML on cognition. METHODS: Nondemented older participants (≥ 50 years; n = 230) underwent cognitive evaluation, fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and resting state functional magnetic resonance imaging (fMRI)...
October 27, 2018: Alzheimer's Research & Therapy
Seung-Hwan Lee, Kyungdo Han, Hanna Cho, Yong-Moon Park, Hyuk-Sang Kwon, Gunseog Kang, Kun-Ho Yoon, Mee Kyoung Kim
BACKGROUND: Variability in biological parameters has been reported to be associated with adverse health outcomes. We aimed to investigate the composite effect of the visit-to-visit variability in blood pressure, glucose, cholesterol, and body mass index on the risk of dementia. METHODS: A population-based cohort study including 2,930,816 subjects without a history of dementia, hypertension, diabetes mellitus, and dyslipidemia who underwent ≥ 3 health examinations was performed...
October 27, 2018: Alzheimer's Research & Therapy
Petr Novak, Reinhold Schmidt, Eva Kontsekova, Branislav Kovacech, Tomas Smolek, Stanislav Katina, Lubica Fialova, Michal Prcina, Vojtech Parrak, Peter Dal-Bianco, Martin Brunner, Wolfgang Staffen, Michael Rainer, Matej Ondrus, Stefan Ropele, Miroslav Smisek, Roman Sivak, Norbert Zilka, Bengt Winblad, Michal Novak
BACKGROUND: Neurofibrillary pathology composed of tau protein is closely correlated with severity and phenotype of cognitive impairment in patients with Alzheimer's disease and non-Alzheimer's tauopathies. Targeting pathological tau proteins via immunotherapy is a promising strategy for disease-modifying treatment of Alzheimer's disease. Previously, we reported a 24-week phase 1 trial on the active vaccine AADvac1 against pathological tau protein; here, we present the results of a further 72 weeks of follow-up on those patients...
October 24, 2018: Alzheimer's Research & Therapy
Philip Scheltens, Merja Hallikainen, Timo Grimmer, Thomas Duning, Alida A Gouw, Charlotte E Teunissen, Alle Meije Wink, Paul Maruff, John Harrison, Caroline M van Baal, Suzanne Bruins, Inge Lues, Niels D Prins
BACKGROUND: PQ912 is an inhibitor of the glutaminyl cyclase enzyme that plays a central role in the formation of synaptotoxic pyroglutamate-A-beta oligomers. We report on the first clinical study with PQ912 in subjects with biomarker-proven Alzheimer's disease (AD). The aim was to determine the maximal tolerated dose, target occupancy and treatment-related pharmacodynamic effects. The exploratory efficacy readouts selected were tailored to the patient population with early AD. The therapeutic approach focuses on synaptic dysfunction as captured by various measures such as electroencephalography (EEG), synaptic biomarkers and sensitive cognitive tests...
October 12, 2018: Alzheimer's Research & Therapy
Lara Paracchini, Luca Beltrame, Lucia Boeri, Federica Fusco, Paolo Caffarra, Sergio Marchini, Diego Albani, Gianluigi Forloni
BACKGROUND: The typical familial form of Alzheimer's disease (FAD) accounts for about 5% of total Alzheimer's disease (AD) cases. Presenilins (PSEN1 and PSEN2) and amyloid-β (A4) precursor protein (APP) genes carry all reported FAD-linked mutations. However, other genetic loci may be involved in AD. For instance, seizure-related gene 6 (SEZ6) has been reported in brain development and psychiatric disorders and is differentially expressed in the cerebrospinal fluid of AD cases. METHODS: We describe a targeted exome sequencing analysis of a large Italian kindred with AD, negative for PSEN and APP variants, that indicated the SEZ6 heterozygous mutation R615H is associated with the pathology...
October 12, 2018: Alzheimer's Research & Therapy
Milan Stoiljkovic, Craig Kelley, Tamas L Horvath, Mihály Hajós
BACKGROUND: Translational research in Alzheimer's disease (AD) pathology provides evidence that accumulation of amyloid-β and hyperphosphorylated tau, neuropathological hallmarks of AD, is associated with complex disturbances in synaptic and neuronal function leading to oscillatory abnormalities in the neuronal networks that support memory and cognition. Accordingly, our recent study on transgenic TgF344-AD rats modeling AD showed an age-dependent reduction of stimulation-induced oscillations in the hippocampus, and disrupted long-range connectivity together with enhanced neuronal excitability in the cortex, reflected in greatly increased expression of high-voltage spindles, an epileptic absence seizure-like activity...
October 10, 2018: Alzheimer's Research & Therapy
Jana Crum, Jeffrey Wilson, Marwan Sabbagh
BACKGROUND: The efficacy of cholesterol lowering agents, specifically statins, in slowing the rate of decline of cognitive function in Alzheimer's disease (AD) patients is not yet fully understood. Our team's previously published paper showed that patients who used statins demonstrated no increase in cognitive decline in mild cognitive impairment when compared with nonusers. Further, AD patients on statins demonstrated a slight decreasing trend in cognitive decline. The purpose of this study is therefore to investigate the association between stain use in AD confirmed by clinical diagnosis and autopsy and the pathological burden (plaques, tangles, Braak stage)...
October 2, 2018: Alzheimer's Research & Therapy
Mara Ten Kate, Alberto Redolfi, Enrico Peira, Isabelle Bos, Stephanie J Vos, Rik Vandenberghe, Silvy Gabel, Jolien Schaeverbeke, Philip Scheltens, Olivier Blin, Jill C Richardson, Regis Bordet, Anders Wallin, Carl Eckerstrom, José Luis Molinuevo, Sebastiaan Engelborghs, Christine Van Broeckhoven, Pablo Martinez-Lage, Julius Popp, Magdalini Tsolaki, Frans R J Verhey, Alison L Baird, Cristina Legido-Quigley, Lars Bertram, Valerija Dobricic, Henrik Zetterberg, Simon Lovestone, Johannes Streffer, Silvia Bianchetti, Gerald P Novak, Jerome Revillard, Mark F Gordon, Zhiyong Xie, Viktor Wottschel, Giovanni Frisoni, Pieter Jelle Visser, Frederik Barkhof
BACKGROUND: With the shift of research focus towards the pre-dementia stage of Alzheimer's disease (AD), there is an urgent need for reliable, non-invasive biomarkers to predict amyloid pathology. The aim of this study was to assess whether easily obtainable measures from structural MRI, combined with demographic data, cognitive data and apolipoprotein E (APOE) ε4 genotype, can be used to predict amyloid pathology using machine-learning classification. METHODS: We examined 810 subjects with structural MRI data and amyloid markers from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, including subjects with normal cognition (CN, n = 337, age 66...
September 27, 2018: Alzheimer's Research & Therapy
Elizabeth Finger, Scott Berry, Jeffrey Cummings, Kristy Coleman, Robin Hsiung, Howard H Feldman, Adam Boxer
BACKGROUND: There are currently no treatments for empathy deficits in neuropsychiatric disorders. Acute administration of the hormone oxytocin has been associated with symptomatic improvements across animal models and several neuropsychiatric disorders, but results of the majority of oxytocin randomised controlled trials (RCTs) of longer duration have been negative or inconclusive. This lack of efficacy of may be due to rapid habituation to oxytocin with chronic dosing. The objective of the present study is to describe the design of a phase 2 adaptive randomised controlled crossover trial of intranasal oxytocin in frontotemporal dementia (FOXY) as an efficient model for future investigations of symptomatic treatments in neuropsychiatric and neurodegenerative disorders...
September 27, 2018: Alzheimer's Research & Therapy
Susanne Ostrowitzki, Robert A Lasser, Ernest Dorflinger, Philip Scheltens, Frederik Barkhof, Tania Nikolcheva, Elizabeth Ashford, Sylvie Retout, Carsten Hofmann, Paul Delmar, Gregory Klein, Mirjana Andjelkovic, Bruno Dubois, Mercè Boada, Kaj Blennow, Luca Santarelli, Paulo Fontoura
Following publication of the original article [1], the author reported errors in the formatting of the table. The details of the errors are as follows.
September 27, 2018: Alzheimer's Research & Therapy
Na-Yeon Jung, Hanna Cho, Yeo Jin Kim, Hee Jin Kim, Jong Min Lee, Seongbeom Park, Sung Tae Kim, Eun-Joo Kim, Jae Seung Kim, Seung Hwan Moon, Jae-Hong Lee, Michael Ewers, Duk L Na, Sang Won Seo
BACKGROUND: The protective effect of education has been well established in Alzheimer's disease, whereas its role in patients with isolated cerebrovascular diseases remains unclear. We examined the correlation of education with cortical thickness and cerebral small vessel disease markers in patients with pure subcortical vascular mild cognitive impairment (svMCI) and patients with pure subcortical vascular dementia (SVaD). METHODS: We analyzed 45 patients with svMCI and 47 patients with SVaD with negative results on Pittsburgh compound B positron emission tomographic imaging who underwent structural brain magnetic resonance imaging...
September 27, 2018: Alzheimer's Research & Therapy
Emily A Largent, Jason Karlawish, Joshua D Grill
BACKGROUND: Global leaders have set an ambitious goal of developing interventions to effectively treat or prevent Alzheimer's disease by 2025. CASE PRESENTATION: Achieving this goal will require clinical trials to test promising interventions, yet Alzheimer's researchers are confronting a clinical trial recruitment crisis. One reason for this is that Alzheimer's disease trials must enroll "dyads" composed of both a participant and his or her study partner...
September 27, 2018: Alzheimer's Research & Therapy
Umesh Gangishetti, J Christina Howell, Richard J Perrin, Natalia Louneva, Kelly D Watts, Alexander Kollhoff, Murray Grossman, David A Wolk, Leslie M Shaw, John C Morris, John Q Trojanowski, Anne M Fagan, Steven E Arnold, William T Hu
BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by neuropathologic changes involving beta-amyloid (Aβ), tau, neuronal loss, and other associated biological events. While levels of cerebrospinal fluid (CSF) Aβ and tau peptides have enhanced the antemortem detection of AD-specific changes, these two markers poorly reflect the severity of cognitive and functional deficits in people with altered Aβ and tau levels. While multiple previous studies identified non-Aβ, non-tau proteins as candidate neurodegenerative markers to inform the A/T/N biomarker scheme of AD, few have advanced beyond association with clinical AD diagnosis...
September 25, 2018: Alzheimer's Research & Therapy
Clayton J Vesperman, Vincent Pozorski, Ryan J Dougherty, Lena L Law, Elizabeth Boots, Jennifer M Oh, Catherine L Gallagher, Cynthia M Carlsson, Howard A Rowley, Yue Ma, Barbara B Bendlin, Sanjay Asthana, Mark A Sager, Bruce P Hermann, Sterling C Johnson, Dane B Cook, Ozioma C Okonkwo
BACKGROUND: Age is the cardinal risk factor for Alzheimer's disease (AD), and white matter hyperintensities (WMH), which are more prevalent with increasing age, may contribute to AD. Higher cardiorespiratory fitness (CRF) has been shown to be associated with cognitive health and decreased burden of AD-related brain alterations in older adults. Accordingly, the aim of this study was to determine whether CRF attenuates age-related accumulation of WMH in middle-aged adults at risk for AD...
September 24, 2018: Alzheimer's Research & Therapy
Stephen Salloway, Lee A Honigberg, William Cho, Michael Ward, Michel Friesenhahn, Flavia Brunstein, Angelica Quartino, David Clayton, Deborah Mortensen, Tobias Bittner, Carole Ho, Christina Rabe, Stephen P Schauer, Kristin R Wildsmith, Reina N Fuji, Shehnaaz Suliman, Eric M Reiman, Kewei Chen, Robert Paul
BACKGROUND: We investigated the effect of crenezumab, a humanized anti-amyloid-beta (Aβ) immunoglobulin (Ig)G4 monoclonal antibody, on biomarkers of amyloid pathology, neurodegeneration, and disease progression in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: This double-blind, placebo-controlled, randomized phase II study enrolled patients with mild-to-moderate AD and a Mini-Mental State Examination (MMSE) score of 18-26. In part 1 of the study, patients were 2:1 randomized to receive low-dose subcutaneous (SC) 300 mg crenezumab every 2 weeks (q2w) or placebo for 68 weeks; in part 2, patients were 2:1 randomized to receive high-dose intravenous (IV) 15 mg/kg crenezumab every 4 weeks (q4w) or placebo for 68 weeks...
September 19, 2018: Alzheimer's Research & Therapy
Sylvie L Lesuis, Lianne Hoeijmakers, Aniko Korosi, Susanne R de Rooij, Dick F Swaab, Helmut W Kessels, Paul J Lucassen, Harm J Krugers
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a high prevalence among the elderly and a huge personal and societal impact. Recent epidemiological studies have indicated that the incidence and age of onset of sporadic AD can be modified by lifestyle factors such as education, exercise, and (early) stress exposure. Early life adversity is known to promote cognitive decline at a later age and to accelerate aging, which are both primary risk factors for AD...
September 19, 2018: Alzheimer's Research & Therapy
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