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Alzheimer's & Dementia: Translational Research & Clinical Interventions

Gwendolien Vanderschaeghe, Jolien Schaeverbeke, Rose Bruffaerts, Rik Vandenberghe, Kris Dierickx
In the field of Alzheimer's disease research, the use of biomarkers such as amyloid positron emission tomography (PET) has become widespread over a relatively brief period of time. There is an increasing tendency in research studies and trials to switch from no disclosure under any condition toward a qualified disclosure of individual research results, such as amyloid PET scan results. This perspective article aims to evaluate the possible need for a modification of the available recommendations on amyloid PET scan disclosure, based on recent empirical evidence obtained within the field of amyloid PET...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Michael Gold, Joan Amatniek, Maria C Carrillo, Jesse M Cedarbaum, James A Hendrix, Bradley B Miller, Julie M Robillard, J Jeremy Rice, Holly Soares, Maria B Tome, Ioannis Tarnanas, Gabriel Vargas, Lisa J Bain, Sara J Czaja
Digital technology is transforming the development of drugs for Alzheimer's disease and was the topic of the Alzheimer's Association's Research Roundtable on its May 23-24, 2017 meeting. Research indicates that wearable devices and unobtrusive passive sensors that enable the collection of frequent or continuous, objective, and multidimensional data during daily activities may capture subtle changes in cognition and functional capacity long before the onset of dementia. The potential to exploit these technologies to improve clinical trials as both recruitment and retention tools as well as for potential end points was discussed...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Stephane Epelbaum, Vincent Bouteloup, Jean F Mangin, Valentina La Corte, Raffaela Migliaccio, Hugo Bertin, Marie O Habert, Clara Fischer, Chabha Azouani, Ludovic Fillon, Marie Chupin, Bruno Vellas, Florence Pasquier, Jean F Dartigues, Fréderic Blanc, Audrey Gabelle, Mathieu Ceccaldi, Pierre Krolak-Salmon, Jacques Hugon, Olivier Hanon, Olivier Rouaud, Renaud David, Genevieve Chêne, Bruno Dubois, Carole Dufouil
Introduction: The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory. Methods: We investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose-positron emission tomography evaluations...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Maurizio Severino, Mithula Sivasaravanaparan, Louise Ø Olesen, Christian U von Linstow, Athanasios Metaxas, Elena V Bouzinova, Asif Manzoor Khan, Kate L Lambertsen, Alicia A Babcock, Jan Bert Gramsbergen, Ove Wiborg, Bente Finsen
Introduction: Treatment with selective serotonin reuptake inhibitors has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to an antidepressant mechanism of action. Methods: We investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates Aβ pathology in plaque-bearing double-transgenic amyloid precursor protein (APP)swe /presenilin 1 (PS1)ΔE9 mutants. In addition, we addressed whether serotonin depletion affects Aβ pathology...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Jeffrey Cummings, Garam Lee, Aaron Ritter, Kate Zhong
Introduction: Treatments for Alzheimer's disease (AD) are needed due to the growing number of individuals with preclinical, prodromal, and dementia forms of AD. Drug development for AD therapies can be examined by inspecting the drug development pipeline as represented on Methods: was assessed as of January 30, 2018 to determine AD therapies represented in phase I, phase II, and phase III. Results: There are 112 agents in the current AD treatment pipeline...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Hinesh Topiwala, Graciela Muniz Terrera, Lucy Stirland, Kathryn Saunderson, Tom C Russ, Marshall F Dozier, Craig W Ritchie
Introduction: Lifestyle factors may influence brain health in midlife. Functional magnetic resonance imaging is a widely used tool to investigate early changes in brain health, including neurodegeneration. In this systematic review, we evaluate the relationship between lifestyle factors and neurodegeneration in midlife, as expressed using functional magnetic resonance imaging. Methods: We searched MEDLINE, EMBASE, and PsycINFO combining subject headings and free text terms adapted for each database...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Tiffini Voss, Jerry Li, Jeffrey Cummings, Martin Farlow, Christopher Assaid, Samar Froman, Heather Leibensperger, Linda Snow-Adami, Kerry Budd McMahon, Michael Egan, David Michelson
Introduction: We evaluated the selective M1 muscarinic positive allosteric modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease. Methods: A randomized, double-blind, proof-of-concept trial was performed. Participants with mild-to-moderate Alzheimer's disease, being treated with an acetylcholinesterase inhibitor, were randomized 1:1 to 45 mg of MK-7622 or placebo for 24 weeks. Endpoints included the mean change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11 ) at 12 weeks and Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory at 24 weeks...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Taygan Yilmaz, Roos J Jutten, Cláudia Y Santos, Kimberly A Hernandez, Peter J Snyder
Introduction: Discontinuation and nonpublication of interventional clinical trials represents a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in patients afflicted by mild cognitive impairment and Alzheimer's disease. Methods: We conducted a retrospective, cross-sectional study on mild cognitive impairment and Alzheimer's disease-based interventional clinical trials in ClinicalTrials...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Pierre N Tariot, Francisco Lopera, Jessica B Langbaum, Ronald G Thomas, Suzanne Hendrix, Lon S Schneider, Silvia Rios-Romenets, Margarita Giraldo, Natalia Acosta, Carlos Tobon, Claudia Ramos, Alejandro Espinosa, William Cho, Michael Ward, David Clayton, Michael Friesenhahn, Howard Mackey, Lee Honigberg, Sandra Sanabria Bohorquez, Kewei Chen, Trisha Walsh, Carolyn Langlois, Eric M Reiman
Introduction: Autosomal-dominant Alzheimer's disease (ADAD) represents a crucial population for identifying prevention strategies that might modify disease course for cognitively unimpaired individuals at high imminent risk for developing symptoms due to Alzheimer's disease (AD), that is, who have "preclinical" AD. Crenezumab is an antiamyloid monoclonal antibody that binds monomeric and aggregated forms of amyloid β, with highest affinity for oligomers; it is in development for early stages of sporadic AD and for ADAD...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Linda M P Wesselman, Ann-Katrin Schild, Nina Coll-Padros, Wieke E van der Borg, Judith H P Meurs, Astrid M Hooghiemstra, Rosalinde E R Slot, Lena Sannemann, Lorena Rami, José Luis Molinuevo, Femke H Bouwman, Frank Jessen, Wiesje M van der Flier, Sietske A M Sikkes
Introduction: Individuals with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease and could benefit from a prevention strategy targeting lifestyle factors. Making a program available through the Internet gives a widespread reach at low cost, but suboptimal adherence is a major threat to effectiveness. As a first step in developing an online lifestyle program (OLP), we aimed to identify factors that are barriers and/or facilitators for the use of an OLP in individuals with SCD in three European countries...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Rebecca J Kamil, Dara Bakar, Matthew Ehrenburg, Scott Frankenthaler, Eric X Wei, Eric Anson, Esther Oh, Yuri Agrawal
Introduction: Falls are a significant problem among older adults with Alzheimer's disease, leading to high rates of fracture, hospitalization, and death. Tracking falls in older adults, particularly those with cognitive impairment, is a clinical and research challenge. Methods: This prospective pilot study evaluated the feasibility of a text message program to track falls among patients with dementia. We also compared this technique with the calendar method of fall data collection...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Hiroyuki Kobayashi, Heii Arai
Introduction: Few studies have focused on the association between donepezil and physical comorbid conditions in Alzheimer's disease patients. Methods: We investigated the association between donepezil prescription and the occurrences of comorbidities in Alzheimer's disease patients, by using an electronic medical records database which contains case-based information on approximately three million patients from more than 60 hospitals across Japan. Results: Nine thousand seven hundred forty-nine patients had at least one diagnosis of Alzheimer's disease between 2001 and 2015...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Glen M Doniger, Michal Schnaider Beeri, Alex Bahar-Fuchs, Amihai Gottlieb, Anastasia Tkachov, Hagar Kenan, Abigail Livny, Yotam Bahat, Hadar Sharon, Oran Ben-Gal, Maya Cohen, Gabi Zeilig, Meir Plotnik
Introduction: Ubiquity of Alzheimer's disease (AD) coupled with relatively ineffectual pharmacologic treatments has spurred interest in nonpharmacologic lifestyle interventions for prevention or risk reduction. However, evidence of neuroplasticity notwithstanding, there are few scientifically rigorous, ecologically relevant brain training studies focused on building cognitive reserve in middle age to protect against cognitive decline. This pilot study will examine the ability of virtual reality (VR) cognitive training to improve cognition and cerebral blood flow (CBF) in middle-aged individuals at high AD risk due to parental history...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Jianping Jia, Cuibai Wei, Shuoqi Chen, Fangyu Li, Yi Tang, Wei Qin, Lu Shi, Min Gong, Hui Xu, Fang Li, Jia He, Haiqing Song, Shanshan Yang, Aihong Zhou, Fen Wang, Xiumei Zuo, Changbiao Chu, Junhua Liang, Longfei Jia, Serge Gauthier
Introduction: No licensed medications are available to treat vascular dementia (VaD). Methods: Patients were randomly assigned to experimental groups (SaiLuoTong [SLT] 360 or 240 mg for groups A and B for 52 weeks, respectively) or placebo group (SLT 360 mg and 240 mg for group C only from weeks 27 to 52, respectively). Results: Three hundred twenty-five patients were included in final analysis. At week 26, the difference in VaD Assessment Scale-cognitive subscale scores was 2...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Sandra Weintraub, Maria C Carrillo, Sarah Tomaszewski Farias, Terry E Goldberg, James A Hendrix, Judith Jaeger, David S Knopman, Jessica B Langbaum, Denise C Park, Michael T Ropacki, Sietske A M Sikkes, Kathleen A Welsh-Bohmer, Lisa J Bain, Robert Brashear, Kumar Budur, Ana Graf, Ferenc Martenyi, Marta Segardahl Storck, Christopher Randolph
The Alzheimer's Association's Research Roundtable met in November 2016 to explore how best to measure changes in cognition and function in the preclinical stage of Alzheimer's disease. This review will cover the tools and instruments currently available to identify populations for prevention trials, and measure subtle disease progression in the earliest stages of Alzheimer's disease, and will include discussions of suitable cognitive, behavioral, functional, composite, and biological endpoints for prevention trials...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Guillaume Blivet, Johann Meunier, Francois J Roman, Jacques Touchon
Introduction: Photobiomodulation was assessed as a novel treatment of Alzheimer's disease (AD) by the use of a new device RGn500 combining photonic and magnetic emissions in a mouse model of AD. Methods: Following the injection of amyloid β 25-35 peptide in male Swiss mice, RGn500 was applied once a day for 7 days either on the top of the head or the center of abdomen or both. Results: RGn500 daily application for 10 min produced a neuroprotective effect on the neurotoxic effects of amyloid β 25-35 peptide injection when this type of photobiomodulation was applied both on the head and on the abdomen...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Yun-Fei Chen, Xiao Ni, Adam S Fleisher, Wei Zhou, Paul Aisen, Richard Mohs
Introduction: In clinical trials of Alzheimer's disease, a mixed-model repeated measure approach often serves as the primary analysis when evaluating disease progression; a slope model may be secondary. Methods: Longitudinal change from baseline (14-item version of Alzheimer's Disease Assessment Scale-Cognitive Subscale) was simulated for treatment/placebo from multivariate normal distributions with the variance-covariance matrix estimated from solanezumab trial data...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Andrew F Teich, Ekta Sharma, Eliza Barnwell, Hong Zhang, Agnieszka Staniszewski, Tadanobu Utsuki, Vasudevaraju Padmaraju, Cheryl Mazell, Apostolia Tzekou, Kumar Sambamurti, Ottavio Arancio, Maria L Maccecchini
Introduction: Translational inhibition of amyloid precursor protein (APP) by Posiphen has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of Alzheimer's disease. Methods: We used a mouse model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics. Results: Posiphen treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin-1 mice, without affecting their visual acuity, motor skills, or motivation and without affecting wild-type mice...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Matthew K Taylor, Debra K Sullivan, Jonathan D Mahnken, Jeffrey M Burns, Russell H Swerdlow
Introduction: We assessed the feasibility and cognitive effects of a ketogenic diet (KD) in participants with Alzheimer's disease. Methods: The Ketogenic Diet Retention and Feasibility Trial featured a 3-month, medium-chain triglyceride-supplemented KD followed by a 1-month washout in clinical dementia rating (CDR) 0.5, 1, and 2 participants. We obtained urine acetoacetate, serum β-hydroxybutyrate, food record, and safety data. We administered the Alzheimer's Disease Assessment Scale-cognitive subscale and Mini-Mental State Examination before the KD, and following the intervention and washout...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Felicia Hui En Tay, Claire L Thompson, Chih Ming Nieh, Chih Chiang Nieh, Hui Mien Koh, Jessie Joon Cheen Tan, Philip Lin Kiat Yap
Introduction: Patients with dementia (PWDs) are often subjected to enforced dependency and experience functional decline and emotional distress during hospital stay. Person-centered care (PCC) with specialized psychosocial interventions, minimally obtrusive medical care, and physical restraints-free practice holds potential to improve patient outcomes. We evaluate the effectiveness of an acute hospital dementia unit (Care for Acute Mentally Infirm Elders [CAMIE]) that adopts a PCC protocol...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
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