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Alzheimer's & Dementia: Translational Research & Clinical Interventions

Jefferson W Kinney, Shane M Bemiller, Andrew S Murtishaw, Amanda M Leisgang, Arnold M Salazar, Bruce T Lamb
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques and neurofibrillary tangles. Over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD. The sustained activation of the brain's resident macrophages (microglia) and other immune cells has been demonstrated to exacerbate both amyloid and tau pathology and may serve as a link in the pathogenesis of the disorder...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Rachel L Nosheny, Monica R Camacho, Philip S Insel, Derek Flenniken, Juliet Fockler, Diana Truran, Shannon Finley, Aaron Ulbricht, Paul Maruff, Kristine Yaffe, R Scott Mackin, Michael W Weiner
Introduction: Methods for efficiently identifying cognitive decline and Alzheimer's disease (AD) are a critical unmet need. The goal of this work was to validate novel online study partner (SP)-reported outcomes to identify cognitive decline in older adults. Methods: In older adults enrolled in the Brain Health Registry, we analyzed associations between SP-reported cognitive decline, measured by the Everyday Cognition Scale, and either (1) participant cognition, assessed by Cogstate Brief Battery or (2) participant-reported diagnosis of mild cognitive impairment or AD...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Haifeng Zhang, Jing Wang, Tingting Sun, Zhijiang Wang, Xiaozhen Lyu, Xin Yu, Huali Wang
Introduction: Cognitive training has attracted considerable attention as a safe, economical, and scalable nonpharmacologic intervention in patients with mild cognitive impairment (MCI). However, no study has yet placed sufficient emphasis on the training of executive function. The present study aimed to evaluate whether memory training combined with executive training could lead to improved cognitive and noncognitive performance in patients with MCI. Furthermore, we will explore the neural correlates underlying the changed performances...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Ziheng Hu, Lirong Wang, Shifan Ma, Levent Kirisci, Zhiwei Feng, Ying Xue, William E Klunk, M Ilyas Kamboh, Robert A Sweet, James Becker, Qianzhou Lv, Oscar L Lopez, Xiang-Qun Xie
Introduction: We investigated the effect of antihypertensive (aHTN) medications and cholinesterase inhibitors (ChEIs) on the cognitive decline in patients with Alzheimer's disease (AD) and analyzed synergism by chemogenomics systems pharmacology mapping. Methods: We compared the effect of aHTN drugs on Mini-Mental State Examination scores in 617 AD patients with hypertension, and studied the synergistic effects. Results: The combination of diuretics, calcium channel blockers, and renin-angiotensin-aldosterone system blockers showed slower cognitive decline compared with other aHTN groups (Δβ = +1...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Edward Hill, Peter Clifton, Alicia M Goodwill, Lorraine Dennerstein, Stephen Campbell, Cassandra Szoeke
Introduction: Evidence indicates that associations between diet and Alzheimer's disease may occur through biomarker pathways such as amyloid-β (Aβ); however, few studies have investigated dietary/Aβ relationships, and no study has investigated this relationship in women. Methods: Dietary patterns were extrapolated for 115 participants from the Women's Health Aging Project. Aβ deposition was measured via in vivo F-18 florbetaben positron emission tomography scanning...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Nina Rosenqvist, Ayodeji A Asuni, Christian R Andersson, Søren Christensen, Justus A Daechsel, Jan Egebjerg, Jeppe Falsig, Lone Helboe, Pia Jul, Fredrik Kartberg, Lars Ø Pedersen, Einar M Sigurdsson, Florence Sotty, Karsten Skjødt, Jeffrey B Stavenhagen, Christiane Volbracht, Jan T Pedersen
Introduction: The abnormal hyperphosphorylation of the microtubule-associated protein tau plays a crucial role in neurodegeneration in Alzheimer's disease (AD) and other tauopathies. Methods: Highly specific and selective anti-pS396-tau antibodies have been generated using peptide immunization with screening against pathologic hyperphosphorylated tau from rTg4510 mouse and AD brains and selection in in vitro and in vivo tau seeding assays. Results: The antibody C10...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Roslyn G Poulos, Meredith Gresham, Claire M O'Connor, Christopher J Poulos
No abstract text is available yet for this article.
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Cynthia Chen, Julie M Zissimopoulos
Introduction: Disparities in dementia prevalence across racial/ethnic groups in the United States may not be narrowing over time. Methods: Data from Health and Retirement Study (2000 to 2012) were analyzed. Dementia was ascertained based on cognitive, functional measures. Logistic regression was used to quantify association between dementia and risk factors, including chronic conditions, use of drug treatment for them, separately for whites, blacks, and Hispanics...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Jennifer A Deal, Adele M Goman, Marilyn S Albert, Michelle L Arnold, Sheila Burgard, Theresa Chisolm, David Couper, Nancy W Glynn, Theresa Gmelin, Kathleen M Hayden, Thomas Mosley, James S Pankow, Nicholas Reed, Victoria A Sanchez, A Richey Sharrett, Sonia D Thomas, Josef Coresh, Frank R Lin
Introduction: Hearing impairment is highly prevalent and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders study is a multicenter randomized controlled trial to determine efficacy of hearing treatment in reducing cognitive decline in older adults. Identifier: NCT03243422. Methods: Eight hundred fifty participants without dementia aged 70 to 84 years with mild-to-moderate hearing impairment recruited from four United States field sites and randomized 1:1 to a best-practices hearing intervention or health education control...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Mythily Srinivasan, Niloy Lahiri, Anish Thyagarajan, Emily Witek, Debra Hickman, Debomoy K Lahiri
Introduction: Glucocorticoid-induced leucine zipper is a regulatory protein that sequesters activated nuclear factor-kappa B p65. Previously, we showed that rationally designed analogs of the p65-binding domain of glucocorticoid-induced leucine zipper, referred to as glucocorticoid-induced leucine zipper analogs (GAs), inhibited amyloid β-induced metabolic activity and inflammatory cytokines in mixed brain cell cultures. Here, we investigate the therapeutic efficacy of GA in an Alzheimer's disease model...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Gwen C Marchand, Jonathan C Hilpert, Kristine M Bragg, Jeffrey Cummings
Introduction: The purpose of this study was to describe collaborative research in neuroscience within the context of the Center for Neurodegeneration and Translational Neuroscience (CNTN), a Center of Biomedical Research Excellence supported by the National Institute of General Medical Science. Drawing upon research on the science of team science, this study investigated the way that interactions around research emerged over the course of establishing a new research center. The objectives were to document changes in research activity and describe how human research support infrastructure functioned to support the production of science...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Arlene J Astell, Sarah K Smith, Stephen Potter, Emily Preston-Jones
Introduction: Group-based cognitive stimulation is the only nonpharmacologic intervention recommended by the UK National Institute for Clinical and Health Excellence for people with dementia. The potential of technology to extend the availability of group-based cognitive stimulation has not been tested. Methods: One hundred sixty-one people with dementia participated in an eight-session group activity using Computer Interactive Reminiscence and Conversation Aid (CIRCA)...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Camila Vieira Ligo Teixeira, Thiago Junqueira Ribeiro de Rezende, Marina Weiler, Thamires Naela Cardoso Magalhães, Ana Flávia Mac Knight Carletti-Cassani, Thiago Quinaglia Araújo Costa Silva, Helena Passarelli Giroud Joaquim, Leda Leme Talib, Orestes Vicente Forlenza, Mariana Pires Franco, Pedro Eduardo Nechio, Paula Teixeira Fernandes, Fernando Cendes, Marcio Luis Figueredo Balthazar
Introduction: Information about how physical exercise affects patients with amnestic mild cognitive impairment (aMCI) due to Alzheimer's disease (AD) is still missing. This study evaluated the impact of multicomponent exercise training on cognition and brain structure in aMCI subjects with cerebral spinal fluid positive AD biomarkers. Methods: Forty aMCI subjects were divided in training (multicomponent exercise thrice a week for 6 months) and nontraining groups...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Kyrana Tsapkini, Kimberly T Webster, Bronte N Ficek, John E Desmond, Chiadi U Onyike, Brenda Rapp, Constantine E Frangakis, Argye E Hillis
Introduction: Transcranial direct current stimulation (tDCS) has been recently shown to improve language outcomes in primary progressive aphasia (PPA) but most studies are small and the influence of PPA variant is unknown. Methods: Thirty-six patients with PPA participated in a randomized, sham-controlled, double-blind, within-subject crossover design for 15 daily sessions of stimulation coupled with written naming/spelling therapy. Outcome measures were letter accuracy of treated and untreated words immediately after and at 2 weeks and 2 months posttreatment...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Kelsey N Spalding-Wilson, Edmarie Guzmán-Vélez, Jade Angelica, Kelsey Wiggs, Anya Savransky, Daniel Tranel
Introduction: Caregivers of individuals with dementia are at heightened risk for stress-related mental and physical illnesses, and this problem is growing. There is a critical need to develop effective interventions for caregivers. This study tested whether a 2-day intervention improved psychological health in caregivers of individuals with dementia. Methods: Family caregivers (N = 104) were randomly assigned to a 2-day intervention or wait-list control group...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Rebecca E Amariglio, Rachel F Buckley, Elizabeth C Mormino, Gad A Marshall, Keith A Johnson, Dorene M Rentz, Reisa A Sperling
Introduction: To investigate whether baseline subjective cognitive complaints (SCCs) predict longitudinal decline on neuropsychological testing and whether SCC increases longitudinally, in the setting of high levels of amyloid burden. Methods: Two hundred seventy-nine clinically normal older participants (mean age = 73.7 ± 6.1 years) from the Harvard Aging Brain Study, a cohort of community-dwelling individuals, were followed longitudinally (4.27 ± 1.35 years) with annual subjective memory questionnaires and neuropsychological assessment...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Ece Bayram, Jessica Z K Caldwell, Sarah J Banks
Alzheimer's disease (AD) is caused by a cascade of changes to brain integrity. Neuroimaging biomarkers are important in diagnosis and monitoring the effects of interventions. As memory impairments are among the first symptoms of AD, the relationship between imaging findings and memory deficits is important in biomarker research. The most established magnetic resonance imaging (MRI) finding is hippocampal atrophy, which is related to memory decline and currently used as a diagnostic criterion for AD. While the medial temporal lobes are impacted early by the spread of neurofibrillary tangles, other networks and regional changes can be found quite early in the progression...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Surbhi Sharma, Richard J Young, Jingchun Chen, Xiangning Chen, Edwin C Oh, Martin R Schiller
Minimotifs are modular contiguous peptide sequences in proteins that are important for posttranslational modifications, binding to other molecules, and trafficking to specific subcellular compartments. Some molecular functions of proteins in cellular pathways can be predicted from minimotif consensus sequences identified through experimentation. While a role for minimotifs in regulating signal transduction and gene regulation during disease pathogenesis (such as infectious diseases and cancer) is established, the therapeutic use of minimotif mimetic drugs is limited...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Brent Bluett, Sarah Banks, Dietmar Cordes, Ece Bayram, Virendra Mishra, Jeffrey Cummings, Irene Litvan
Introduction: Freezing of gait (FOG) is a disabling phenomenon characterized by a brief, episodic absence or reduction of forward progression of the feet despite the intention to walk. It is a common cause of falls and mortality in cases with Parkinson's disease (PD). This article reviews neuropsychological and neuroimaging studies to date and introduces a new study of multimodal imaging and cognition in PD-FOG. Methods: A comprehensive literature search identified studies using neuropsychological evaluation and/or neuroimaging to evaluate PD-FOG...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Dietmar Cordes, Xiaowei Zhuang, Muhammad Kaleem, Karthik Sreenivasan, Zhengshi Yang, Virendra Mishra, Sarah J Banks, Brent Bluett, Jeffrey L Cummings
Introduction: Previous neuroimaging studies of Parkinson's disease (PD) patients have shown changes in whole-brain functional connectivity networks. Whether connectivity changes can be detected in the early stages (first 3 years) of PD by resting-state functional magnetic resonance imaging (fMRI) remains elusive. Research infrastructure including MRI and analytic capabilities is required to investigate this issue. The National Institutes of Health/National Institute of General Medical Sciences Center for Biomedical Research Excellence awards support infrastructure to advance research goals...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
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