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Alzheimer's & Dementia: Translational Research & Clinical Interventions

Chee-Jen Chang, Tse-Chih Chou, Chiung-Chih Chang, Ta-Fu Chen, Chaur-Jong Hu, Jong-Ling Fuh, Wenfu Wang, Chiung-Mei Chen, Winco Hsu, Chin-Chang Huang
Introduction: The objective of the study was to assess adherence and persistence of patients treated with rivastigmine versus donepezil. Methods: Persistence was calculated as the time from the first prescription date of rivastigmine/donepezil until discontinuation/medication switch/end of available data, whichever occurred first. Adherence was calculated as proportion of days covered and medication possession ratio. Results: A majority of patients persisted on 4...
2019: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Christopher L H Chen, Purabi Reang Sharma, Boon Yeow Tan, Casuarine Low, Narayanaswamy Venketasubramanian
Background: Dementia is a large and growing health care burden globally, and its major cause is Alzheimer's disease (AD). MLC901 (Neuroaid II) is a simplified form of MLC601 (Neuroaid), a Traditional Chinese Medicine with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury. MLC601 has been shown to modulate amyloid precursor protein (APP) processing in human neuroblastoma cell cultures and increase the levels of soluble APPα. In addition, MLC901 has been shown to reduce tau phosphorylation in vitro...
2019: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Chantal Vidal, Kelly Daescu, Keely E Fitzgerald, Anna Starokadomska, Ilya Bezprozvanny, Li Zhang
Introduction: Heme is a central molecule in mitochondrial respiration and ATP generation in neuronal cells. Thus, we assessed the importance of altered heme metabolism in Alzheimer's disease (AD) pathogenesis. Methods: To investigate the role of altered heme metabolism in AD, we identified heme-related proteins whose expression is altered in AD patients and mouse models exhibiting amyloid pathology. We detected the levels of proteins involved in heme synthesis, uptake, degradation, and function during neuronal differentiation and characterized the effects of Aβ...
2019: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Michael Grundman, Roger Morgan, Jason D Lickliter, Lon S Schneider, Steven DeKosky, Nicholas J Izzo, Robert Guttendorf, Michelle Higgin, Julie Pribyl, Kelsie Mozzoni, Hank Safferstein, Susan M Catalano
Background: Elayta (CT1812) is a novel allosteric antagonist of the sigma-2 receptor complex that prevents and displaces binding of Aβ oligomers to neurons. By stopping a key initiating event in Alzheimer's disease, this first-in-class drug candidate mitigates downstream synaptotoxicity and restores cognitive function in aged transgenic mouse models of Alzheimer's disease. Methods: A phase 1, two-part single and multiple ascending dose study was conducted in 7 and 4 cohorts of healthy human subjects, respectively...
2019: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Robert J Lucero, Elizabeth A Fehlberg, Aditi G M Patel, Ragnhildur I Bjarnardottir, Renessa Williams, Karis Lee, Margaret Ansell, Suzanne Bakken, Jose A Luchsinger, Mary Mittelman
Introduction: Information and communication technology (ICT) has emerged as promising to support health care consumers, including informal caregivers. This systematic review seeks to evaluate the state of the science of ICT interventions on the health of informal dementia caregivers. Methods: We searched PubMed, CINAHL, Web of Science, and PsycINFO using concepts associated with ICT, dementia, and caregiver. Studies were assessed using the Quality Assessment Tool for Quantitative Studies...
2019: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Atsushi Iwata, Takeshi Iwatsubo, Ryoko Ihara, Kazushi Suzuki, Yutaka Matsuyama, Naoki Tomita, Hiroyuki Arai, Kenji Ishii, Michio Senda, Kengo Ito, Takeshi Ikeuchi, Ryozo Kuwano, Hiroshi Matsuda
Introduction: The objective of this study was to determine whether sex or education level affects the longitudinal rate of cognitive decline in Japanese patients in the Alzheimer's disease Neuroimaging Initiative study with defined mild cognitive impairment (MCI). Methods: We accessed the entire Japanese Alzheimer's Disease Neuroimaging Initiative data set of 537 individuals, among whom 234 had MCI and 149 had Alzheimer's disease. We classified participants into three categories of educational history: (1) low, 0 to 9 years; (2) moderate, 10 to 15 years; and (3) high ≥16 years...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Antoine Lutz, Olga M Klimecki, Fabienne Collette, Géraldine Poisnel, Eider Arenaza-Urquijo, Natalie L Marchant, Vincent De La Sayette, Géraldine Rauchs, Eric Salmon, Patrick Vuilleumier, Eric Frison, Denis Vivien, Gaël Chételat
Introduction: The Age-Well observational, cross-sectional study investigates the affective and cognitive mechanisms of meditation expertise with behavioral, neuroimaging, sleep, and biological measures sensitive to aging and Alzheimer's disease (AD). Methods: Thirty cognitively unimpaired individuals aged 65 years or older with at least 10,000 hours of practice in mindfulness meditation (MM) and loving-kindness and compassion meditation (LKCM) are selected. The outcomes are the neuroimaging brain correlates of MM and LKCM and the assessments of long-term meditation practices on behavioral, neural, and biological measures as compared to nonmeditator older controls from the Age-Well randomized controlled trial...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Irfan A Qureshi, Giridhar Tirucherai, Michael K Ahlijanian, Gerry Kolaitis, Clifford Bechtold, Michael Grundman
Introduction: Extracellular tau is hypothesized to mediate the onset and progression of tauopathies, including Alzheimer's disease, progressive supranuclear palsy, and a subset of frontotemporal lobar degenerations. A putative strategy for treating these disorders is to reduce extracellular tau levels using tau-directed immunotherapy. The results of the first-in-human study of BIIB092 (formerly BMS-986168/IPN007), a humanized monoclonal antibody that binds to N-terminal tau, are reported here...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Natalie L Marchant, Thorsten Barnhofer, Olga M Klimecki, Géraldine Poisnel, Antoine Lutz, Eider Arenaza-Urquijo, Fabienne Collette, Miranka Wirth, Ann-Katrin Schild, Nina Coll-Padrós, Leslie Reyrolle, Deborah Horney, Pierre Krolak-Salmon, José Luis Molinuevo, Zuzana Walker, Aline Maillard, Eric Frison, Frank Jessen, Gael Chételat
Introduction: Subjectively experienced cognitive decline in older adults is an indicator of increased risk for dementia and is also associated with increased levels of anxiety symptoms. As anxiety is itself emerging as a risk factor for cognitive decline and dementia, the primary question of the present study is whether an 8-week mindfulness-based intervention can significantly reduce anxiety symptoms in patients with subjective cognitive decline (SCD). The secondary questions pertain to whether such changes extend to other domains of psychological, social, and biological functioning (including cognition, self-regulation, lifestyle, well-being and quality of life, sleep, and selected blood-based biomarkers) associated with mental health, older age, and risk for dementia...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Jing Shi, Xuekai Zhang, Jingnian Ni, Mingqing Wei, Ting Li, Bingling Zhou, Xiawei Liu, Liping Zhang, Pengwen Wang, Jinzhou Tian, Yongyan Wang
Introduction: The degeneration of memory-focused synapses play important roles in Alzheimer's disease (AD) pathogenesis, while it is not well known how β amyloid interferes neuron apoptosis and how a herbal combination GAPT influence synapse loss and neuronal apoptosis pathways of APP/PS1 transgenic mice. Methods: Three-month and six-month APPswe/PS1dE9 transgenic mice were used. Spatial and memory ability were measured by Morris Water Maze, Neuron and synapse number were assessed by electron microscope; Aβ, Bcl-2/Bax were determined by immunohistochemistry and western blot...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Géraldine Poisnel, Eider Arenaza-Urquijo, Fabienne Collette, Olga M Klimecki, Natalie L Marchant, Miranka Wirth, Vincent de La Sayette, Géraldine Rauchs, Eric Salmon, Patrik Vuilleumier, Eric Frison, Aline Maillard, Denis Vivien, Antoine Lutz, Gaël Chételat
Introduction: The Age-Well clinical trial is an ongoing monocentric, randomized, controlled trial aiming to assess an 18-month preventive meditation-based intervention directly targeting the attentional and emotional dimensions of aging to promote mental health and well-being in elderly people. Methods: One hundred thirty-seven cognitively unimpaired older adults are randomized to either an 18-month meditation-based intervention, a structurally matched foreign language training, or a passive control arm...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
André Strydom, Antonia Coppus, Rafael Blesa, Adrian Danek, Juan Fortea, John Hardy, Johannes Levin, Georg Nuebling, Anne-Sophie Rebillat, Craig Ritchie, Cornelia van Duijn, Shahid Zaman, Henrik Zetterberg
The discovery that adults with Down syndrome (DS) have neuropathological features identical to individuals with sporadic Alzheimer's disease (AD) played a key role in the identification of the amyloid precursor protein gene on chromosome 21 and resulted in the amyloid cascade hypothesis. Individuals with DS have a lifetime risk for dementia in excess of 90%, and DS is now acknowledged to be a genetic form of AD similar to rare autosomal-dominant causes. Just as DS put the spotlight on amyloid precursor protein mutations, it is also likely to inform us of the impact of manipulating the amyloid pathway on treatment outcomes in AD...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Stina Saunders, Graciela Muniz-Terrera, Julie Watson, Charlotte L Clarke, Saturnino Luz, Alison R Evans, Craig W Ritchie
Introduction: Current pharmacological interventions for Alzheimer's dementia delay symptom progression for about a year. Although the outcomes in earlier disease states may include changes in biomarkers, the clinical effectiveness of any intervention can ultimately only be assessed by a patient's self-reported well-being. A better understanding of earlier manifestations of Alzheimer's disease and the drive for relevant outcome measures, allied to technological advances in artificial intelligence, have mediated the electronic Person-Specific Outcome Measure (ePSOM) development program...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Joseph E Gaugler, Eric Jutkowitz, Colleen M Peterson, Rachel Zmora
Introduction: Although a handful of studies have examined mortality among caregivers of persons with Alzheimer's disease or a related dementia (ADRD), the proportion of caregivers who die before their cognitively impaired care recipients remains unknown. Methods: We conducted descriptive and survival analyses on up to 17 years of data from the nationally representative Health and Retirement Study to evaluate the proportion of spouse caregivers who died before their care recipients...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Guoqiao Wang, Chengjie Xiong, Eric M McDade, Jason Hassenstab, Andrew J Aschenbrenner, Anne M Fagan, Tammie L S Benzinger, Brian A Gordon, John C Morris, Yan Li, Randall J Bateman
Introduction: As the role of biomarkers is increasing in Alzheimer's disease (AD) clinical trials, it is critical to use a comprehensive temporal biomarker profile that reflects both baseline and longitudinal assessments to establish a more precise association between the change in biomarkers and change in cognition. Because age of onset of dementia symptoms is highly predictable, and there are relatively few age-related comorbidities, the Dominantly Inherited Alzheimer Network autosomal dominant AD population affords a unique opportunity to investigate these relationships in a well-characterized population...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Marine Tournissac, Milene Vandal, Cyntia Tremblay, Philippe Bourassa, Sylvie Vancassel, Vincent Emond, Anne Gangloff, Frederic Calon
Introduction: High levels of plasmatic branched-chain amino acids (BCAA), commonly used as dietary supplements, are linked to metabolic risk factors for Alzheimer's disease (AD). BCAA directly influence amino acid transport to the brain and, therefore, neurotransmitter levels. We thus investigated the impact of BCAA on AD neuropathology in a mouse model. Methods: 3xTg-AD mice were fed either a control diet or a high-fat diet from 6 to 18 months of age. For the last 2 months, dietary BCAA content was adjusted to high (+50%), normal (+0%), or low (-50%)...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Chan Shen, Xiaohui Zhao, Nilanjana Dwibedi, R Constance Wiener, Patricia A Findley, Usha Sambamoorthi
Introduction: There is scant literature on the use of opioids among community-dwelling elderly with Alzheimer's disease and related dementias (ADRD). Methods: We adopted a retrospective, cross-sectional study design using Medicare Current Beneficiary Survey data from 2006 to 2013. The study sample included elderly community-dwelling Medicare beneficiaries who were diagnosed with chronic pain conditions and had Medicare fee-for-service plans for the entire year. We conducted bivariate χ2 test and multivariate logistic regression to examine the relationship between opioid use and ADRD status...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Herlind Megges, Silka Dawn Freiesleben, Christina Rösch, Nina Knoll, Lauri Wessel, Oliver Peters
Introduction: The user experience and clinical effectiveness with wearable global positioning system (GPS) devices for persons with dementia (PwDs) and caregivers (CGs) remain unclear although many are available. Methods: Using a crossover design, 20 dyads tested two similar commercial GPS watches (products A and B) at home for 4 weeks each. Usability, product functions, design features and product satisfaction at home and the clinic were investigated. Caregiver burden and quality of life assessed clinical effectiveness...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
S Imindu Liyanage, Clarissa Santos, Donald F Weaver
As the leading cause of dementia worldwide, Alzheimer's disease has garnered intense academic and clinical interest. Yet, trials in search of a disease-modifying therapy have failed overwhelmingly. We suggest that, in part, this may be attributable to the influence of disruptive variables inherent to the framework of a clinical trial. Specifically, we observe that everyday factors such as diet, education, mental exertion, leisure participation, multilingualism, sleep, trauma, and physical activity, as well as clinical/study parameters including environment, family coaching, concurrent medications, and illnesses may serve as potent confounders, disruptors, or sources of bias to an otherwise significant drug-disease interaction...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Bjørn-Eivind Kirsebom, Kaja Nordengen, Per Selnes, Knut Waterloo, Silje Bøen Torsetnes, Berglind Gísladóttir, Britta Brix, Eugeen Vanmechelen, Geir Bråthen, Erik Hessen, Dag Aarsland, Tormod Fladby
Introduction: The cerebrospinal fluid neurogranin (Ng)/β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) ratio may reflect synaptic affection resulting from reduced beta-amyloid (Aβ) clearance. We hypothesize that increased Ng/BACE1 ratio predicts the earliest cognitive decline in Alzheimer's disease. Methods: We compared Ng/BACE1 levels between cases with subjective cognitive decline (n = 18) and mild cognitive impairment (n = 20) both with amyloid plaques and healthy controls ( APOE -ε4+, n = 16; APOE -ε4-, n = 20)...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
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