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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/29747683/reduced-penetrance-of-the-psen1-h163y-autosomal-dominant-alzheimer-mutation-a-22-year-follow-up-study
#1
Steinunn Thordardottir, Elena Rodriguez-Vieitez, Ove Almkvist, Daniel Ferreira, Laure Saint-Aubert, Anne Kinhult-Ståhlbom, Håkan Thonberg, Michael Schöll, Eric Westman, Anders Wall, Maria Eriksdotter, Henrik Zetterberg, Kaj Blennow, Agneta Nordberg, Caroline Graff
BACKGROUND: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years. METHODS: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017...
May 10, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29716655/a-double-blind-placebo-controlled-cross-over-clinical-trial-of-donepezil-in-posterior-cortical-atrophy-due-to-underlying-alzheimer-s-disease-donipad-study
#2
Basil H Ridha, Sebastian Crutch, Dawn Cutler, Christopher Frost, William Knight, Suzie Barker, Norah Epie, Elizabeth K Warrington, Riitta Kukkastenvehmas, Jane Douglas, Martin N Rossor
BACKGROUND: The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease. METHODS: A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks...
May 1, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29695305/cross-sectional-associations-of-plasma-vitamin-d-with-cerebral-%C3%AE-amyloid-in-older-adults-at-risk-of-dementia
#3
Fati Nourhashemi, Claudie Hooper, Christelle Cantet, Catherine Féart, Isabelle Gennero, Pierre Payoux, Anne Sophie Salabert, Sophie Guyonnet, Philipe De Souto Barreto, Bruno Vellas
BACKGROUND: Vitamin D deficiency is associated with an increased risk of Alzheimer's disease and increased beta-amyloid (Aβ) in animals. Hence we sought to investigate the relationship between plasma 25-hydroxyvitamin D (25(OH)D) and cerebral Aβ in older adults with subjective memory complaints. METHODS: This is a secondary analysis of the Multidomain Alzheimer Preventive Trial. Participants were 178 dementia-free individuals aged 70 years or older with data on plasma 25(OH)D and cerebral Aβ load assessed by [18 F]-florbetapir positron emission tomography...
April 25, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29695300/a-language-based-sum-score-for-the-course-and-therapeutic-intervention-in-primary-progressive-aphasia
#4
Elisa Semler, Sarah Anderl-Straub, Ingo Uttner, Janine Diehl-Schmid, Adrian Danek, Beate Einsiedler, Klaus Fassbender, Klaus Fliessbach, Hans-Jürgen Huppertz, Holger Jahn, Johannes Kornhuber, Bernhard Landwehrmeyer, Martin Lauer, Rainer Muche, Johannes Prudlo, Anja Schneider, Matthias L Schroeter, Albert C Ludolph, Markus Otto
BACKGROUND: With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions...
April 25, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29695292/a-biomarker-study-in-long-lasting-amnestic-mild-cognitive-impairment
#5
Chiara Cerami, Alessandra Dodich, Sandro Iannaccone, Giuseppe Magnani, Roberto Santangelo, Luca Presotto, Alessandra Marcone, Luigi Gianolli, Stefano F Cappa, Daniela Perani
BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous syndrome resulting from Alzheimer's disease (AD) as well as to non-AD and non-neurodegenerative conditions. A subset of patients with amnestic MCI (aMCI) present with an unusually long-lasting course, a slow rate of clinical neuropsychological progression, and evidence of focal involvement of medial temporal lobe structures. In the present study, we explored positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a sample of subjects with aMCI with such clinical features in order to provide in vivo evidence to improve disease characterisation in this subgroup...
April 25, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29690919/lack-of-human-like-extracellular-sortilin-neuropathology-in-transgenic-alzheimer-s-disease-model-mice-and-macaques
#6
Feng-Qin Zhou, Juan Jiang, Chelsea M Griffith, Peter R Patrylo, Huaibin Cai, Yaping Chu, Xiao-Xin Yan
BACKGROUND: Alzheimer's disease (AD) is a devastating neurodegenerative disorder bearing multiple pathological hallmarks suggestive of complex cellular/molecular interplay during pathogenesis. Transgenic mice and nonhuman primates are used as disease models for mechanistic and translational research into AD; the extent to which these animal models recapitulate AD-type neuropathology is an issue of importance. Putative C-terminal fragments from sortilin, a member of the vacuolar protein sorting 10 protein (Vps10p) family, have recently been shown to deposit in the neuritic β-amyloid (Aβ) plaques in the human brain...
April 24, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29631614/neurofilament-light-as-a-blood-biomarker-for-neurodegeneration-in-down-syndrome
#7
Andre Strydom, Amanda Heslegrave, Carla M Startin, Kin Y Mok, John Hardy, Jurgen Groet, Dean Nizetic, Henrik Zetterberg
BACKGROUND: Down syndrome (DS) may be considered a genetic form of Alzheimer's disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions. METHODS: We measured blood NF-L concentrations in 100 adults with DS using Simoa NF-light® assays, and we examined relationships with age as well as cross-sectional and longitudinal dementia diagnosis...
April 10, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29622037/a-phase-2-clinical-trial-of-pf-05212377-sam-760-in-subjects-with-mild-to-moderate-alzheimer-s-disease-with-existing-neuropsychiatric-symptoms-on-a-stable-daily-dose-of-donepezil
#8
Terence Fullerton, Brendon Binneman, William David, Marielle Delnomdedieu, James Kupiec, Peter Lockwood, Jessica Mancuso, Jeffrey Miceli, Joanne Bell
BACKGROUND: Symptomatic benefits have been reported for 5-HT6 receptor antagonists in Alzheimer's disease (AD) trials. SAM-760 is a potent and selective 5-HT6 receptor antagonist that has demonstrated central 5-HT6 receptor saturation in humans at a dose of 30 mg. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial evaluating the efficacy and safety of SAM-760 30 mg once daily (QD) for 12 weeks in subjects with AD on a stable regimen of donepezil 5 to 10 mg QD...
April 5, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29622034/the-impact-of-group-activities-and-their-content-on-persons-with-dementia-attending-them
#9
Jiska Cohen-Mansfield
BACKGROUND: Individuals suffering from dementia and residing in nursing homes often feel lonely and bored. This study examined the engagement and mood of people with dementia in group activities, and how personal characteristics, such as cognitive function, may impact on an individual's responses to group activities. METHODS: The study included 102 participants, who took part in group activities while their mood and engagement levels were observed. Participants were invited to attend 10 different types of group activities, each of which was offered twice...
April 5, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29615123/representativeness-of-european-clinical-trial-populations-in-mild-alzheimer-s-disease-dementia-a-comparison-of-18-month-outcomes-with-real-world-data-from-the-geras-observational-study
#10
Catherine Reed, Mark Belger, Grazia Dell'Agnello, Kristin Kahle-Wrobleski, Gopalan Sethuraman, Ann Hake, Joel Raskin, David Henley
BACKGROUND: Comparison of disease progression between placebo-group patients from randomised controlled trials (RCTs) and real-world patients can aid in assessing the generalisability of RCT outcomes. This analysis compared outcomes between community-dwelling patients with mild Alzheimer's disease (AD) dementia from two RCTs (pooled European (EU) data from EXPEDITION and EXPEDITION 2) and similar patients from the EU GERAS observational study. METHODS: Data from placebo-group patients with mild AD dementia from the RCTs (EU countries only) were compared with data from GERAS patients with mild AD dementia...
April 3, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29615111/metabolic-correlates-of-reserve-and-resilience-in-mci-due-to-alzheimer-s-disease-ad
#11
Matteo Bauckneht, Andrea Chincarini, Roberta Piva, Dario Arnaldi, Nicola Girtler, Federico Massa, Matteo Pardini, Matteo Grazzini, Hulya Efeturk, Marco Pagani, Gianmario Sambuceti, Flavio Nobili, Silvia Morbelli
BACKGROUND: We explored the presence of both reserve and resilience in late-converter mild cognitive impairment due to Alzheimer's disease (MCI-AD) and in patients with slowly progressing amyloid-positive MCI by assessing the topography and extent of neurodegeneration with respect to both "aggressive" and typically progressing phenotypes and in the whole group of patients with MCI, grounding the stratification on education level. METHODS: We analyzed 94 patients with MCI-AD followed until conversion to dementia and 39 patients with MCI who had brain amyloidosis (AMY+ MCI), all with available baseline18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) results...
April 3, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29609632/naming-is-not-explaining-future-directions-for-the-cognitive-reserve-and-brain-maintenance-theories
#12
REVIEW
Jonna Nilsson, Martin Lövdén
Contemporary imaging measures of the human brain explain less than half of the differences in cognitive functioning and change among older adults. Researchers have advanced several theories and concepts to guide research that aims to better explain these individual differences in cognitive aging. Taking the fundamental measurement model in the empirical sciences as a starting point, we here scrutinize two such complementary theories, brain maintenance and cognitive reserve, in an attempt to clarify these theories, gauge their usefulness, and identify ways in which they can be further developed...
April 2, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29559004/diagnostic-value-of-cerebrospinal-fluid-tau-neurofilament-and-progranulin-in-definite-frontotemporal-lobar-degeneration
#13
Joery Goossens, Maria Bjerke, Sara Van Mossevelde, Tobi Van den Bossche, Johan Goeman, Bart De Vil, Anne Sieben, Jean-Jacques Martin, Patrick Cras, Peter Paul De Deyn, Christine Van Broeckhoven, Julie van der Zee, Sebastiaan Engelborghs
BACKGROUND: We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes. METHODS: CSF levels of routine AD biomarkers (phosphorylated tau (p-tau181 ), total tau (t-tau), and amyloid-beta (Aβ)1-42 ) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20)...
March 20, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29558986/addition-of-the-a%C3%AE-42-40-ratio-to-the-cerebrospinal-fluid-biomarker-profile-increases-the-predictive-value-for-underlying-alzheimer-s-disease-dementia-in-mild-cognitive-impairment
#14
Inês Baldeiras, Isabel Santana, Maria João Leitão, Helena Gens, Rui Pascoal, Miguel Tábuas-Pereira, José Beato-Coelho, Diana Duro, Maria Rosário Almeida, Catarina Resende Oliveira
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aβ42/40 ratio would improve MCI categorization and more accurately predict progression to AD...
March 20, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29558979/cerebrospinal-fluid-in-the-differential-diagnosis-of-alzheimer-s-disease-clinical-utility-of-an-extended-panel-of-biomarkers-in-a-specialist-cognitive-clinic
#15
Ross W Paterson, Catherine F Slattery, Teresa Poole, Jennifer M Nicholas, Nadia K Magdalinou, Jamie Toombs, Miles D Chapman, Michael P Lunn, Amanda J Heslegrave, Martha S Foiani, Philip S J Weston, Ashvini Keshavan, Jonathan D Rohrer, Martin N Rossor, Jason D Warren, Catherine J Mummery, Kaj Blennow, Nick C Fox, Henrik Zetterberg, Jonathan M Schott
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias. METHODS: We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls...
March 20, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29544527/white-paper-by-the-society-for-csf-analysis-and-clinical-neurochemistry-overcoming-barriers-in-biomarker-development-and-clinical-translation
#16
REVIEW
Charlotte E Teunissen, Markus Otto, Sebastiaan Engelborghs, Sanna-Kaisa Herukka, Sylvain Lehmann, Piotr Lewczuk, Alberto Lleó, Armand Perret-Liaudet, Hayrettin Tumani, Martin R Turner, Marcel M Verbeek, Jens Wiltfang, Henrik Zetterberg, Lucilla Parnetti, Kaj Blennow
Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e...
March 15, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29530075/prospective-associations-between-pulse-pressure-and-cognitive-performance-in-chinese-middle-aged-and-older-population-across-a-5-year-study-period
#17
Tingting Sha, Wenwei Cheng, Yan Yan
BACKGROUND: Substantial evidence indicates that the relationship between blood pressure (BP) measures and cognitive functioning is inconsistent, complex, and age-related. Pulse pressure (PP), which can not only reflect arterial stiffness and but also represent the chronic effects of hypertension other than BP itself, has been considered as a better predictor of cognitive impairment. However, evidence on the association of cognitive function with PP has not been investigated extensively...
March 12, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29510747/the-left-frontal-cortex-supports-reserve-in-aging-by-enhancing-functional-network-efficiency
#18
Nicolai Franzmeier, Julia Hartmann, Alexander N W Taylor, Miguel Á Araque-Caballero, Lee Simon-Vermot, Lana Kambeitz-Ilankovic, Katharina Bürger, Cihan Catak, Daniel Janowitz, Claudia Müller, Birgit Ertl-Wagner, Robert Stahl, Martin Dichgans, Marco Duering, Michael Ewers
BACKGROUND: Recent evidence derived from functional magnetic resonance imaging (fMRI) studies suggests that functional hubs (i.e., highly connected brain regions) are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer's disease. These results suggest that LFC connectivity supports reserve capacity, alleviating memory decline...
March 6, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29490691/improving-the-identification-of-dementia-with-lewy-bodies-in-the-context-of-an-alzheimer-s-type-dementia
#19
Alan J Thomas, Fariba Mahin-Babaei, Mohammad Saidi, Debbie Lett, John Paul Taylor, Lauren Walker, Johannes Attems
BACKGROUND: Dementia due to Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two most common neurodegenerative causes of dementia. They commonly occur together, especially in older people, but clinical identification of these diseases in dementia is difficult in such circumstances. We therefore conducted a study using cases with both comprehensive prospective clinical assessments and complete neuropathological examination to determine if it is possible to identify such mixed cases clinically and to determine features which may identify DLB in the presence of AD dementia...
March 1, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29490669/thiamine-diphosphate-reduction-strongly-correlates-with-brain-glucose-hypometabolism-in-alzheimer-s-disease-whereas-amyloid-deposition-does-not
#20
Shaoming Sang, Xiaoli Pan, Zhichun Chen, Fan Zeng, Shumei Pan, Huimin Liu, Lirong Jin, Guoqiang Fei, Changpeng Wang, Shuhua Ren, Fangyang Jiao, Weiqi Bao, Weiyan Zhou, Yihui Guan, Yiqiu Zhang, Hongcheng Shi, Yanjiang Wang, Xiang Yu, Yun Wang, Chunjiu Zhong
BACKGROUND: The underlying mechanism of brain glucose hypometabolism, an invariant neurodegenerative feature that tightly correlates with cognitive impairment and disease progression of Alzheimer's disease (AD), remains elusive. METHODS: Positron emission tomography with 2-[18 F]fluoro-2-deoxy-D-glucose (FDG-PET) was used to evaluate brain glucose metabolism, presented as the rate of 2-[18 F]fluoro-2-deoxy-D-glucose standardized uptake value ratio (FDG SUVR) in patients with AD or control subjects and in mice with or without thiamine deficiency induced by a thiamine-deprived diet...
March 1, 2018: Alzheimer's Research & Therapy
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