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Alzheimer's Research & Therapy

Lutz Frölich, Glen Wunderlich, Claus Thamer, Michael Roehrle, Miguel Garcia, Bruno Dubois
BACKGROUND: There are currently no approved treatments for the prodromal stage of Alzheimer's disease (AD). Approved symptomatic treatments for mild-to-moderate AD include acetylcholinesterase inhibitors and memantine, but more efficacious treatments are needed. BI 409306 is a potent and selective phosphodiesterase 9 inhibitor assessed for the symptomatic treatment of AD. Efficacy and safety of BI 409306 was analysed in two phase II proof-of-concept clinical trials in cognitive impairment associated with prodromal AD (study 1) and mild AD (study 2)...
February 12, 2019: Alzheimer's Research & Therapy
Bernard J Hanseeuw, Francisco Lopera, Reisa A Sperling, Daniel J Norton, Edmarie Guzman-Velez, Ana Baena, Enmanuelle Pardilla-Delgado, Aaron P Schultz, Jennifer Gatchel, David Jin, Kewei Chen, Eric M Reiman, Keith A Johnson, Yakeel T Quiroz
BACKGROUND: Autosomal dominant Alzheimer's disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-β deposition. To determine whether striatal Pittsburgh compound B (PiB)-PET measurements of amyloid-β can help predict disease severity in ADAD, we compared relationships of striatal and neocortical PiB-PET to age, tau-PET, and memory performance in the Colombian Presenilin 1 E280A kindred. METHODS: Fourteen carriers (age = 28-42, Mini-Mental State Examination = 26-30) and 20 age-matched non-carriers were evaluated using PiB, flortaucipir (FTP; tau), and memory testing (CERAD Word List Learning)...
February 4, 2019: Alzheimer's Research & Therapy
Lorenza Magno, Christian B Lessard, Marta Martins, Verena Lang, Pedro Cruz, Yasmine Asi, Matilda Katan, Jamie Bilsland, Tammaryn Lashley, Paramita Chakrabarty, Todd E Golde, Paul J Whiting
BACKGROUND: Recent Genome Wide Association Studies (GWAS) have identified novel rare coding variants in immune genes associated with late onset Alzheimer's disease (LOAD). Amongst these, a polymorphism in phospholipase C-gamma 2 (PLCG2) P522R has been reported to be protective against LOAD. PLC enzymes are key elements in signal transmission networks and are potentially druggable targets. PLCG2 is highly expressed in the hematopoietic system. Hypermorphic mutations in PLCG2 in humans have been reported to cause autoinflammation and immune disorders, suggesting a key role for this enzyme in the regulation of immune cell function...
February 2, 2019: Alzheimer's Research & Therapy
Fatemah A Sakr, Michel J Grothe, Enrica Cavedo, Irina Jelistratova, Marie-Odile Habert, Martin Dyrba, Gabriel Gonzalez-Escamilla, Hugo Bertin, Maxime Locatelli, Stephane Lehericy, Stefan Teipel, Bruno Dubois, Harald Hampel
BACKGROUND: Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer's disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual's amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC)...
January 31, 2019: Alzheimer's Research & Therapy
Omar A Halawa, Jennifer R Gatchel, Rebecca E Amariglio, Dorene M Rentz, Reisa A Sperling, Keith A Johnson, Gad A Marshall
BACKGROUND: A decline in instrumental activities of daily living (IADL) correlates with the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia and has been associated with frontal and parietal hypometabolism, lower cerebrospinal fluid amyloid β1-42 , and inferior temporal cortical thinning. Identifying the underlying biomarkers of functional decline will allow for the early identification of individuals at risk of disease progression. OBJECTIVE: To investigate the association between IADL impairment and in vivo regional cerebral tau and cortical amyloid deposition across clinically normal (CN) elderly, MCI, and AD dementia...
January 31, 2019: Alzheimer's Research & Therapy
Richard M Tsai, Alexandre Bejanin, Orit Lesman-Segev, Renaud LaJoie, Adrienne Visani, Viktoriya Bourakova, James P O'Neil, Mustafa Janabi, Suzanne Baker, Suzee E Lee, David C Perry, Lynn Bajorek, Anna Karydas, Salvatore Spina, Lea T Grinberg, William W Seeley, Eliana M Ramos, Giovanni Coppola, Maria Luisa Gorno-Tempini, Bruce L Miller, Howard J Rosen, William Jagust, Adam L Boxer, Gil D Rabinovici
BACKGROUND: The tau positron emission tomography (PET) ligand 18 F-flortaucipir binds to paired helical filaments of tau in aging and Alzheimer's disease (AD), but its utility in detecting tau aggregates in frontotemporal dementia (FTD) is uncertain. METHODS: We performed 18 F-flortaucipir imaging in patients with the FTD syndromes (n = 45): nonfluent variant primary progressive aphasia (nfvPPA) (n = 11), corticobasal syndrome (CBS) (n = 10), behavioral variant frontotemporal dementia (bvFTD) (n = 10), semantic variant primary progressive aphasia (svPPA) (n = 2) and FTD associated pathogenic genetic mutations microtubule-associated protein tau (MAPT) (n = 6), chromosome 9 open reading frame 72 (C9ORF72) (n = 5), and progranulin (GRN) (n = 1)...
January 31, 2019: Alzheimer's Research & Therapy
Gemma Salvadó, Anna Brugulat-Serrat, Carole H Sudre, Oriol Grau-Rivera, Marc Suárez-Calvet, Carles Falcon, Karine Fauria, M Jorge Cardoso, Frederik Barkhof, José Luis Molinuevo, Juan Domingo Gispert
BACKGROUND: White matter hyperintensities (WMH) of presumed vascular origin have been associated with an increased risk of Alzheimer's disease (AD). This study aims to describe the patterns of WMH associated with dementia risk estimates and individual risk factors in a cohort of middle-aged/late middle-aged individuals (mean 58 (interquartile range 51-64) years old). METHODS: Magnetic resonance imaging and AD risk factors were collected from 575 cognitively unimpaired participants...
January 24, 2019: Alzheimer's Research & Therapy
Yeo Jin Kim, Seong-Kyoung Cho, Hee Jin Kim, Jin San Lee, Juyoun Lee, Young Kyoung Jang, Jacob W Vogel, Duk L Na, Changsoo Kim, Sang Won Seo
BACKGROUND: Although amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer's disease, patients with aMCI show heterogeneous patterns of progression. Moreover, there are few studies investigating data-driven cognitive trajectory in aMCI. We therefore classified patients with aMCI based on their cognitive trajectory, measured by clinical dementia rating sum of boxes (CDR-SOB). Then, we compared the clinical and neuroimaging features among groups classified by cognitive trajectory...
January 22, 2019: Alzheimer's Research & Therapy
Anette Hall, Timo Pekkala, Tuomo Polvikoski, Mark van Gils, Miia Kivipelto, Jyrki Lötjönen, Jussi Mattila, Mia Kero, Liisa Myllykangas, Mira Mäkelä, Minna Oinas, Anders Paetau, Hilkka Soininen, Maarit Tanskanen, Alina Solomon
BACKGROUND: We developed multifactorial models for predicting incident dementia and brain pathology in the oldest old using the Vantaa 85+ cohort. METHODS: We included participants without dementia at baseline and at least 2 years of follow-up (N = 245) for dementia prediction or with autopsy data (N = 163) for pathology. A supervised machine learning method was used for model development, considering sociodemographic, cognitive, clinical, vascular, and lifestyle factors, as well as APOE genotype...
January 22, 2019: Alzheimer's Research & Therapy
Greg J Elder, Sean J Colloby, Michael J Firbank, Ian G McKeith, John-Paul Taylor
BACKGROUND: Complex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages. METHODS: The study was a randomised, double-blind, placebo-controlled trial involving 40 participants with LBD (Mage  = 75...
January 18, 2019: Alzheimer's Research & Therapy
Steffen Wolfsgruber, José Luis Molinuevo, Michael Wagner, Charlotte E Teunissen, Lorena Rami, Nina Coll-Padrós, Femke H Bouwman, Rosalinde E R Slot, Linda M P Wesselman, Oliver Peters, Katja Luther, Katharina Buerger, Josef Priller, Christoph Laske, Stefan Teipel, Annika Spottke, Michael T Heneka, Emrah Düzel, Alexander Drzezga, Jens Wiltfang, Sietske A M Sikkes, Wiesje M van der Flier, Frank Jessen
INTRODUCTION: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer's disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD)...
January 17, 2019: Alzheimer's Research & Therapy
Lucilla Parnetti, Elena Chipi, Nicola Salvadori, Katia D'Andrea, Paolo Eusebi
BACKGROUND: Alzheimer's disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer's Association (NIA-AA) criteria, followed by mild cognitive impairment (MCI), a featured clinical entity defined as "due to AD", or "prodromal AD", when pathophysiological biomarkers (i.e., cerebrospinal fluid or positron emission tomography with amyloid tracer) are positive...
January 15, 2019: Alzheimer's Research & Therapy
Alireza Nazarian, Anatoliy I Yashin, Alexander M Kulminski
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in the elderly and the sixth leading cause of death in the United States. AD is mainly considered a complex disorder with polygenic inheritance. Despite discovering many susceptibility loci, a major proportion of AD genetic variance remains to be explained. METHODS: We investigated the genetic architecture of AD in four publicly available independent datasets through genome-wide association, transcriptome-wide association, and gene-based and pathway-based analyses...
January 12, 2019: Alzheimer's Research & Therapy
Wai Hang Cheng, Kris M Martens, Asma Bashir, Honor Cheung, Sophie Stukas, Ebrima Gibbs, Dhananjay R Namjoshi, Emily B Button, Anna Wilkinson, Carlos J Barron, Neil R Cashman, Peter A Cripton, Cheryl L Wellington
BACKGROUND: The annual incidence of traumatic brain injury (TBI) in the United States is over 2.5 million, with approximately 3-5 million people living with chronic sequelae. Compared with moderate-severe TBI, the long-term effects of mild TBI (mTBI) are less understood but important to address, particularly for contact sport athletes and military personnel who have high mTBI exposure. The purpose of this study was to determine the behavioural and neuropathological phenotypes induced by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model of mTBI in both wild-type (WT) and APP/PS1 mice up to 8 months post-injury...
January 12, 2019: Alzheimer's Research & Therapy
Gad A Marshall, Sarah L Aghjayan, Maria Dekhtyar, Joseph J Locascio, Kamal Jethwani, Rebecca E Amariglio, Sara J Czaja, David A Loewenstein, Keith A Johnson, Reisa A Sperling, Dorene M Rentz
BACKGROUND: Impairment in instrumental activities of daily living (IADL) may occur in the earliest stages of mild cognitive impairment (MCI). However, there are few reliable measures of IADL in MCI or that have a sufficient range of scores in clinically normal (CN) elderly. The objective of this pilot study was to examine the convergent validity of a phone performance-based IADL instrument, the Harvard Automated Phone Task (APT), designed to measure the earliest IADL changes in Alzheimer's disease (AD), with other sensitive performance-based and subjective measures of everyday functional capacity among CN and MCI participants...
January 10, 2019: Alzheimer's Research & Therapy
Inês Baldeiras, Isabel Santana, Maria João Leitão, Daniela Vieira, Diana Duro, Barbara Mroczko, Johannes Kornhuber, Piotr Lewczuk
BACKGROUND: The previously described and validated Erlangen Score (ES) algorithm enables interpretation of the cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), ordering them on an ordinal scale: from neurochemically normal (ES = 0) through improbable AD (ES = 1), possible AD (ES = 2 or 3), to probable AD (ES = 4). Here we assess the accuracy of the ES in predicting hazards of progression from the mild cognitive impairment (MCI) stage of AD to the dementia stage of the disease (Alzheimer's disease dementia (ADD)) in a novel, single-center cohort...
January 5, 2019: Alzheimer's Research & Therapy
Jürgen Rehm, Omer S M Hasan, Sandra E Black, Kevin D Shield, Michaël Schwarzinger
BACKGROUND: Alcohol use has been identified as a risk factor for dementia and cognitive decline. However, some patterns of drinking have been associated with beneficial effects. METHODS AND RESULTS: To clarify the relationship between alcohol use and dementia, we conducted a scoping review based on a systematic search of systematic reviews published from January 2000 to October 2017 by using Medline, Embase, and PsycINFO. Overall, 28 systematic reviews were identified: 20 on the associations between the level of alcohol use and the incidence of cognitive impairment/dementia, six on the associations between dimensions of alcohol use and specific brain functions, and two on induced dementias...
January 5, 2019: Alzheimer's Research & Therapy
Esther G A Karssemeijer, Justine A Aaronson, Willem J R Bossers, Rogier Donders, Marcel G M Olde Rikkert, Roy P C Kessels
BACKGROUND: Exercise is often proposed as a non-pharmacological intervention to delay cognitive decline in people with dementia, but evidence remains inconclusive. Previous studies suggest that combining physical exercise with cognitive stimulation may be more successful in this respect. Exergaming is a promising intervention in which physical exercise is combined with cognitively challenging tasks in a single session. The aim of this study was to investigate the effect of exergame training and aerobic training on cognitive functioning in older adults with dementia...
January 5, 2019: Alzheimer's Research & Therapy
Kai-Xin Dou, Meng-Shan Tan, Chen-Chen Tan, Xi-Peng Cao, Xiao-He Hou, Qi-Hao Guo, Lan Tan, Vincent Mok, Jin-Tai Yu
BACKGROUND: Cholinesterase inhibitors and memantine have been approved for management of Alzheimer's disease (AD), but there has been no consensus about the choice of various types and doses of drugs at different stages. Hence, we compared and ranked the efficacy and tolerability of these available drugs. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 2017...
December 27, 2018: Alzheimer's Research & Therapy
Nicholas M Vogt, Kymberleigh A Romano, Burcu F Darst, Corinne D Engelman, Sterling C Johnson, Cynthia M Carlsson, Sanjay Asthana, Kaj Blennow, Henrik Zetterberg, Barbara B Bendlin, Federico E Rey
BACKGROUND: Trimethylamine N-oxide (TMAO), a small molecule produced by the metaorganismal metabolism of dietary choline, has been implicated in human disease pathogenesis, including known risk factors for Alzheimer's disease (AD), such as metabolic, cardiovascular, and cerebrovascular disease. METHODS: In this study, we tested whether TMAO is linked to AD by examining TMAO levels in cerebrospinal fluid (CSF) collected from a large sample (n = 410) of individuals with Alzheimer's clinical syndrome (n = 40), individuals with mild cognitive impairment (MCI) (n = 35), and cognitively-unimpaired individuals (n = 335)...
December 22, 2018: Alzheimer's Research & Therapy
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