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Alzheimer frontal variant

Qing Ye, Fan Su, Hao Shu, Liang Gong, Chunming Xie, Zhijun Zhang, Feng Bai
Previous cross-sectional studies that investigated the effects of apolipoprotein E (ApoE) ε4 status on hippocampal networks have shown inconsistent results. Aging is a well-known risk factor for Alzheimer's disease (AD) and could strongly interact with ApoE-related vulnerabilities to affect AD risk. However, no longitudinal data have been published regarding the interaction of the ApoE genotype and aging on hippocampal networks. Fifty-one patients with amnestic-type mild cognitive impairment (aMCI) and 64 matched cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at baseline and at a 35-month follow-up...
October 12, 2016: Brain Imaging and Behavior
Gennady V Roshchupkin, Hieab H Adams, Sven J van der Lee, Meike W Vernooij, Cornelia M van Duijn, Andre G Uitterlinden, Aad van der Lugt, Albert Hofman, Wiro J Niessen, Mohammad A Ikram
The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions...
September 4, 2016: Neurobiology of Aging
Margherita Melloni, Pablo Billeke, Sandra Baez, Eugenia Hesse, Laura de la Fuente, Gonzalo Forno, Agustina Birba, Indira García-Cordero, Cecilia Serrano, Angelo Plastino, Andrea Slachevsky, David Huepe, Mariano Sigman, Facundo Manes, Adolfo M García, Lucas Sedeño, Agustín Ibáñez
Recursive social decision-making requires the use of flexible, context-sensitive long-term strategies for negotiation. To succeed in social bargaining, participants' own perspectives must be dynamically integrated with those of interactors to maximize self-benefits and adapt to the other's preferences, respectively. This is a prerequisite to develop a successful long-term self-other integration strategy. While such form of strategic interaction is critical to social decision-making, little is known about its neurocognitive correlates...
September 27, 2016: Brain: a Journal of Neurology
Harmony Duclos, Vincent de La Sayette, Anne-Laure Bonnet, Armelle Viard, Francis Eustache, Béatrice Desgranges, Mickaël Laisney
Although frontal presentations of Alzheimer's disease (fv-AD) have already been described in the literature, we still know little about patients' social cognitive abilities, especially their theory of mind (ToM). We report the case of FT, a 61-year-old woman who was diagnosed with fv-AD. Two assessments of social cognition, using a false-belief task, the Reading the Mind in the Eyes test, and a task probing knowledge of social norms, were performed one year apart. FT exhibited cognitive ToM and social knowledge deficits from the onset...
September 23, 2016: Journal of Alzheimer's Disease: JAD
Anne Hafkemeijer, Christiane Möller, Elise G P Dopper, Lize C Jiskoot, Annette A van den Berg-Huysmans, John C van Swieten, Wiesje M van der Flier, Hugo Vrenken, Yolande A L Pijnenburg, Frederik Barkhof, Philip Scheltens, Jeroen van der Grond, Serge A R B Rombouts
BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. METHODS: We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63...
September 23, 2016: Journal of Alzheimer's Disease: JAD
Pongsatorn Paholpak, Andrew R Carr, Joseph P Barsuglia, Robin J Barrows, Elvira Jimenez, Grace J Lee, Mario F Mendez
BACKGROUND: While much disinhibition in dementia results from generalized impulsivity, in behavioral variant frontotemporal dementia (bvFTD) disinhibition may also result from impaired social cognition. OBJECTIVE: To deconstruct disinhibition and its neural correlates in bvFTD vs. early-onset Alzheimer's disease (eAD). METHODS: Caregivers of 16 bvFTD and 21 matched-eAD patients completed the Frontal Systems Behavior Scale disinhibition items...
September 19, 2016: Journal of Geriatric Psychiatry and Neurology
Andreas Johnen, Lisa Brandstetter, Christian Kärgel, Heinz Wiendl, Hubertus Lohmann, Thomas Duning
Limb apraxia denotes a cognitive impairment of gesture production. Lesion studies in patients with stroke point towards distinct neural processing streams for limb imitation and object-pantomime within left parietal and temporal cortex, respectively. Despite its frequent occurrence as an early symptom in both, Alzheimer's dementia (AD) and behavioural variant frontotemporal dementia (bvFTD), neural correlates of limb apraxia within these patient groups remain unexplored. Using voxel-based morphometry and multiple regression models, associations between limb apraxia and gray matter (GM) volume were investigated in 36 dementia patients (18 AD, 18 bvFTD) in early disease stages...
August 26, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Maxime Bertoux, Siddharth Ramanan, Andrea Slachevsky, Stephanie Wong, Fernando Henriquez, Gada Musa, Carolina Delgado, Emma Flanagan, Michel Bottlaender, Marie Sarazin, Michael Hornberger, Bruno Dubois
BACKGROUND: Memory impairment in behavioral variant frontotemporal dementia (bvFTD) is traditionally considered to be mild and attributed to prefrontal cortex dysfunction. Recent studies, however, indicated that some patients can present with a memory impairment of the hippocampal type, showing storage and consolidation deficits in addition to the more executive/prefrontal related encoding and strategic difficulties. OBJECTIVE: This study aimed to study the relationship between executive functions (EF) and memory processes in bvFTD via a data-driven approach...
October 4, 2016: Journal of Alzheimer's Disease: JAD
R A Armstrong
Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight...
2016: Folia Neuropathologica
Alexandra M Nicholson, Rosa Rademakers
Frontotemporal lobar degeneration is a neurodegenerative disorder affecting over 50,000 people in the United States alone. The most common pathological subtype of FTLD is the presence of ubiquitinated TAR DNA binding protein 43 (TDP-43) accumulations in frontal and temporal brain regions at autopsy. While some cases of FTLD-TDP can be attributed to the inheritance of disease-causing mutations, the majority of cases arise with no known genetic cause. In 2010, the first genome-wide association study was conducted in patients with FTLD-TDP to determine potential genetic risk factors for this homogenous subgroup of dementia patients, leading to the identification of the TMEM106B locus on chromosome 7...
November 2016: Acta Neuropathologica
Anthony Papegaey, Sabiha Eddarkaoui, Vincent Deramecourt, Francisco-Jose Fernandez-Gomez, Pierre Pantano, Hélène Obriot, Camille Machala, Vincent Anquetil, Agnès Camuzat, Alexis Brice, Claude-Alain Maurage, Isabelle Le Ber, Charles Duyckaerts, Luc Buée, Nicolas Sergeant, Valérie Buée-Scherrer
Reduction of Tau protein expression was described in 2003 by Zhukareva et al. in a variant of frontotemporal lobar degeneration (FTLD) referred to as diagnosis of dementia lacking distinctive histopathology, then re-classified as FTLD with ubiquitin inclusions. However, the analysis of Tau expression in FTLD has not been reconsidered since then. Knowledge of the molecular basis of protein aggregates and genes that are mutated in the FTLD spectrum would enable to determine whether the "Tau-less" is a separate pathological entity or if it belongs to an existing subclass of FTLD...
2016: Acta Neuropathologica Communications
Lihua Qiu, Yong He, Hehan Tang, Yi Zhou, Jinhong Wang, Weiwei Zhang, Guangxiang Chen, Fei Zhao, Tingxue Ouyang, Bin Ju, Zhengyan Li, Lanlan Wang, Ling Zou, Qiyong Gong
: Several genome-wide association studies have found that the rs11136000 polymorphism of the C allele (CLU-C) is associated with the risk for developing late-onset Alzheimer's disease (LOAD). However, the effects of the CLU-C/C genotype on brain structure, including gray and white matter, are not adequately understood. OBJECTIVES: We aimed to clarify the gray matter and white matter integrity changes in non-demented ageing individuals with the AD risk gene of the rs11136000 polymorphism of the C allele (CLU-C) and the correlation with cognitive performance...
July 3, 2016: Current Alzheimer Research
Maria-Letizia Campanari, Francisco Navarrete, Stephen D Ginsberg, Jorge Manzanares, Javier Sáez-Valero, María-Salud García-Ayllón
Alzheimer's disease (AD) is characterized by a decrease in the enzymatic activity of the enzyme acetylcholinesterase (AChE). AChE is expressed as multiple splice variants, which may serve both cholinergic degradative functions and non-cholinergic functions unrelated with their capacity to hydrolyze acetylcholine. We have recently demonstrated that a prominent pool of enzymatically inactive AChE protein exists in the AD brain. In this study, we analyzed protein and transcript levels of individual AChE variants in human frontal cortex from AD patients by western blot analysis using specific anti-AChE antibodies and by quantitative real-time PCR (qRT-PCR)...
May 30, 2016: Journal of Alzheimer's Disease: JAD
Nadene Dermody, Stephanie Wong, Rebekah Ahmed, Olivier Piguet, John R Hodges, Muireann Irish
Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls...
May 30, 2016: Journal of Alzheimer's Disease: JAD
Sylvia S Fong, Carlos David Navarrete, Sean E Perfecto, Andrew R Carr, Elvira E Jimenez, Mario F Mendez
The personal/impersonal distinction of moral decision-making postulates intuitive emotional responses from medial frontal activity and rational evaluation from lateral frontal activity. This model can be analyzed in behavioral variant frontotemporal dementia (bvFTD), a disorder characterized by impaired emotional intuitions, ventromedial prefrontal cortex involvement, and relative sparing of lateral frontal regions. Moral dilemmas were presented to 10 bvFTD, 11 Alzheimer's disease (AD), and 9 healthy control (HC) participants while recording skin conductance responses, a measure of emotional arousal...
May 6, 2016: Social Neuroscience
Meichen Yu, Alida A Gouw, Arjan Hillebrand, Betty M Tijms, Cornelis Jan Stam, Elisabeth C W van Straaten, Yolande A L Pijnenburg
We investigated whether the functional connectivity and network topology in 69 Alzheimer's disease (AD), 48 behavioral variant of frontotemporal dementia (bvFTD) patients, and 64 individuals with subjective cognitive decline are different using resting-state electroencephalography recordings. Functional connectivity between all pairs of electroencephalography channels was assessed using the phase lag index (PLI). We subsequently calculated PLI-weighted networks, from which minimum spanning trees (MSTs) were constructed...
June 2016: Neurobiology of Aging
Benjamin Cretin, François Sellal, Nathalie Philippi, Olivier Bousiges, Laure Di Bitonto, Catherine Martin-Hunyadi, Frederic Blanc
BACKGROUND: Aside from rare case reports, only one study, with 12 patients, has addressed the phenotypic presentation of epilepsy in clinically defined amnestic mild cognitive impairment (aMCI, presumed to correspond to the AD prodromal stage): the authors highlighted a pharmacosensitive non-convulsive partial epileptic syndrome most probably related to the temporal or temporo-frontal cortices. OBJECTIVE: The objective of this study was to verify the existence and the syndromic features of epileptic prodromal AD in a tertiary Memory Clinic...
April 18, 2016: Journal of Alzheimer's Disease: JAD
Roya Behrouzi, Xiawei Liu, Dongyue Wu, Andrew C Robinson, Sayuri Tanaguchi-Watanabe, Sara Rollinson, Jing Shi, Jinzhou Tian, Hisham H M Hamdalla, John Ealing, Anna Richardson, Matthew Jones, Stuart Pickering-Brown, Yvonne S Davidson, Michael J Strong, Masato Hasegawa, Julie S Snowden, David M A Mann
It has been suggested that patients with motor neurone disease (MND) and those with MND combined with behavioural variant frontotemporal dementia (bvFTD) (ie FTD + MND) or with FTD alone might exist on a continuum based on commonalities of neuropathology and/or genetic risk. Moreover, it has been reported that both a neuronal and a glial cell tauopathy can accompany the TDP-43 proteinopathy in patients with motor neurone disease (MND) with cognitive changes, and that the tauopathy may be fundamental to disease pathogenesis and clinical phenotype...
2016: Acta Neuropathologica Communications
Ramon Landin-Romero, Fiona Kumfor, Cristian E Leyton, Muireann Irish, John R Hodges, Olivier Piguet
BACKGROUND: Clinical differentiation between Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) is challenging due to overlapping clinical features at presentation. Whilst diagnostic criteria for both disorders incorporate evidence of frontal and temporal cortical atrophy, understanding of the progression of atrophy in these disorders is limited. This study aimed to elucidate common and disease-specific progressive changes in cortical and subcortical brain structures in AD and bvFTD...
March 21, 2016: NeuroImage
Chu-Chung Huang, Mu-En Liu, Hung-Wen Kao, Kun-Hsien Chou, Albert C Yang, Ying-Hsiu Wang, Tong-Ru Chen, Shih-Jen Tsai, Ching-Po Lin
Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a SORL1 single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of SORL1 rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between SORL1 rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21-92 years)...
2016: Scientific Reports
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