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Prodromal AD

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https://www.readbyqxmd.com/read/29165085/a-speech-recognition-based-solution-for-the-automatic-detection-of-mild-cognitive-impairment-from-spontaneous-speech
#1
Laszlo Toth, Ildiko Hoffmann, Gabor Gosztolya, Veronika Vincze, Greta Szatloczki, Zoltan Banreti, Magdolna Pakaski, Janos Kalman
BACKGROUND: Even today the reliable diagnosis of the prodromal stages of Alzheimer's disease (AD) remains a great challenge. Our research focuses on the earliest detectable indicators of cognitive decline in mild cognitive impairment (MCI). Since the presence of language impairment has been reported even in the mild stage of AD, the aim of this study is to develop a sensitive neuropsychological screening method which is based on the analysis of spontaneous speech production during performing a memory task...
November 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29164798/regionally-specific-changes-in-the-hippocampal-circuitry-accompany-progression-of-cerebrospinal-fluid-biomarkers-in-preclinical-alzheimer-s-disease
#2
Christine L Tardif, Gabriel A Devenyi, Robert S C Amaral, Sandra Pelleieux, Judes Poirier, Pedro Rosa-Neto, John Breitner, M Mallar Chakravarty
Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau)...
November 21, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/29159051/interactive-versus-additive-relationships-between-regional-cortical-thinning-and-amyloid-burden-in-predicting-clinical-decline-in-mild-ad-and-mci-individuals
#3
Federico d'Oleire Uquillas, Heidi I L Jacobs, Bernard Hanseeuw, Gad A Marshall, Michael Properzi, Aaron P Schultz, Molly R LaPoint, Keith A Johnson, Reisa A Sperling, Patrizia Vannini
The biological mechanisms that link Beta-amyloid (Aβ) plaque deposition, neurodegeneration, and clinical decline in Alzheimer's disease (AD) dementia, have not been completely elucidated. Here we studied whether amyloid accumulation and neurodegeneration, independently or interactively, predict clinical decline over time in a group of memory impaired older individuals [diagnosed with either amnestic mild cognitive impairment (MCI), or mild AD dementia]. We found that baseline Aβ-associated cortical thinning across clusters encompassing lateral and medial temporal and parietal cortices was related to higher baseline Clinical Dementia Rating Sum-of-Boxes (CDR-SB)...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29133888/neuronal-hyperactivity-due-to-loss-of-inhibitory-tone-in-apoe4-mice-lacking-alzheimer-s-disease-like-pathology
#4
Tal Nuriel, Sergio L Angulo, Usman Khan, Archana Ashok, Qiuying Chen, Helen Y Figueroa, Sheina Emrani, Li Liu, Mathieu Herman, Geoffrey Barrett, Valerie Savage, Luna Buitrago, Efrain Cepeda-Prado, Christine Fung, Eliana Goldberg, Steven S Gross, S Abid Hussaini, Herman Moreno, Scott A Small, Karen E Duff
The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason APOE4 is associated with increased AD risk remains a source of debate. Neuronal hyperactivity is an early phenotype in both AD mouse models and in human AD, which may play a direct role in the pathogenesis of the disease. Here, we have identified an APOE4-associated hyperactivity phenotype in the brains of aged APOE mice using four complimentary techniques-fMRI, in vitro electrophysiology, in vivo electrophysiology, and metabolomics-with the most prominent hyperactivity occurring in the entorhinal cortex...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29125488/comparison-between-fcsrt-and-lassi-l-to-detect-early-stage-alzheimer-s-disease
#5
Jordi A Matias-Guiu, María Nieves Cabrera-Martín, Rosie E Curiel, María Valles-Salgado, Teresa Rognoni, Teresa Moreno-Ramos, José Luis Carreras, David A Loewenstein, Jorge Matías-Guiu
BACKGROUND: The Free and Cued Selective Reminding Test (FCSRT) is the most accurate test for the diagnosis of prodromal Alzheimer's disease (AD). Recently, a novel cognitive test, the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), has been developed in order to provide an early diagnosis. OBJECTIVE: To compare the diagnostic accuracy of the FCSRT and the LASSI-L for the diagnosis of AD in its preclinical and prodromal stages using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a reference...
November 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29124109/the-effect-of-diagnostic-criteria-on-outcome-measures-in-preclinical-and-prodromal-alzheimer-s-disease-implications-for-trial-design
#6
Daniela Bertens, Betty M Tijms, Lisa Vermunt, Niels D Prins, Philip Scheltens, Pieter Jelle Visser
Introduction: We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates. Methods: We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal)...
November 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29116145/cingulate-island-sign-temporally-changes-in-dementia-with-lewy-bodies
#7
Tomomichi Iizuka, Rui Iizuka, Masashi Kameyama
The cingulate island sign (CIS) that reflects sparing of the posterior cingulate cortex (PCC) relative to the precuneus plus cuneus on FDG-PET and brain perfusion SPECT, has been proposed as a feature of dementia with Lewy bodies (DLB). As the CIS is influenced by concomitant Alzheimer's disease (AD)-type neurofibrillary tangle (NFT) pathology, we postulated that the CIS gradually disappears as DLB progresses. To determine temporal changes in the CIS, 24 patients with mild DLB and 7 with prodromal DLB underwent (123)I-IMP-SPECT and MMSE twice at an interval of two years...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29067343/alzheimer-s-disease-drug-development-pipeline-2017
#8
REVIEW
Jeffrey Cummings, Garam Lee, Travis Mortsdorf, Aaron Ritter, Kate Zhong
INTRODUCTION: There is an urgent need to develop new treatments for Alzheimer's disease (AD) and to understand the drug development process for new AD therapies. METHODS: We assessed the agents in the AD pipeline as documented in clinicaltrials.gov for phase I, phase II, and phase III, accessed 1/5/2017. RESULTS: There are 105 agents in the AD treatment development pipeline, of which 25 agents are in 29 trials in phase I, 52 agents are in 68 trials in phase II, and 28 agents are in 42 trials in phase III...
September 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29065864/do-some-anxiety-disorders-belong-to-the-prodrome-of-bipolar-disorder-a-clinical-study-combining-retrospective-and-prospective-methods-to-analyse-the-relationship-between-anxiety-disorder-and-bipolar-disorder-from-the-perspective-of-biorhythms
#9
Na Du, Ya-Ling Zhou, Xu Zhang, Jing Guo, Xue-Li Sun
BACKGROUND: In clinical practice, some patients diagnosed with anxiety disorder (AD) may develop bipolar disorder (BD) many years later, and some cases of AD may be cured by the use of mood stabilizers. However, the relationship between AD and BD should be explored further. METHOD: To track how many cases of AD turned to BD and to discover the differences between them, we recruited 48 patients diagnosed with BD, who were assigned to the BD group for the retrospective analysis, and we also recruited 186 patients diagnosed with AD at enrolment; this latter group was asked to complete follow-up surveys conducted 3 months, 6 months, 12 months and 18 months after the primary stage of the study...
October 24, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/29048465/%C3%AE-app-processing-drives-gradual-tau-pathology-in-an-age-dependent-amyloid-rat-model-of-alzheimer-s-disease
#10
Mickael Audrain, Benoit Souchet, Sandro Alves, Romain Fol, Arthur Viode, Alexis Haddjeri, Satoru Tada, Nicola S Orefice, Charlène Joséphine, Alexis-Pierre Bemelmans, Thierry Delzescaux, Nicole Déglon, Philippe Hantraye, Yvette Akwa, François Becher, Jean-Marie Billard, Brigitte Potier, Patrick Dutar, Nathalie Cartier, Jérôme Braudeau
The treatment of Alzheimer's disease (AD) remains challenging and requires a better in depth understanding of AD progression. Particularly, the link between amyloid protein precursor (APP) processing and Tau pathology development remains poorly understood. Growing evidences suggest that APP processing and amyloid-β (Aβ) release are upstream of Tau pathology but the lack of animal models mimicking the slow progression of human AD raised questions around this mechanism. Here, we described that an AD-like βAPP processing in adults wild-type rats, yielding to human APP, βCTF and Aβ levels similar to those observed in AD patients, is sufficient to trigger gradual Tauopathy...
October 18, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28980730/cognitive-changes-in-prodromal-parkinson-s-disease-a-review
#11
REVIEW
Sophie Fengler, Inga Liepelt-Scarfone, Kathrin Brockmann, Eva Schäffer, Daniela Berg, Elke Kalbe
Although other nonmotor phenomena representing possible prodromal symptoms of Parkinson's disease have been described in some detail, the occurrence and characteristics of cognitive decline in this early phase of the disease are less well understood. The aim of this review is to summarize the current state of research on cognitive changes in prodromal PD. Only a small number of longitudinal studies have been conducted that examined cognitive function in individuals with a subsequent PD diagnosis. However, when we consider data from at-risk groups, the evidence suggests that cognitive decline may occur in a substantial number of individuals who have the potential for developing PD...
October 5, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28978335/attitudes-toward-clinical-trials-across-the-alzheimer-s-disease-spectrum
#12
Michelle M Nuño, Daniel L Gillen, Kulwant K Dosanjh, Jenny Brook, David Elashoff, John M Ringman, Joshua D Grill
BACKGROUND: Research has revealed that manifest Alzheimer's disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms...
October 4, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28934374/the-effect-of-white-matter-hyperintensities-on-statistical-analysis-of-diffusion-tensor-imaging-in-cognitively-healthy-elderly-and-prodromal-alzheimer-s-disease
#13
Daniel Svärd, Markus Nilsson, Björn Lampinen, Jimmy Lätt, Pia C Sundgren, Erik Stomrud, Lennart Minthon, Oskar Hansson, Danielle van Westen
Diffusion tensor imaging (DTI) has been used to study microstructural white matter alterations in a variety of conditions including normal aging and Alzheimer's disease (AD). White matter hyperintensities (WMH) are common in cognitively healthy elderly as well as in AD and exhibit elevated mean diffusivity (MD) and reduced fractional anisotropy (FA). However, the effect of WMH on statistical analysis of DTI estimates has not been thoroughly studied. In the present study we address this in two ways. First, we investigate the effect of WMH on MD and FA in the dorsal and ventral cingulum, the superior longitudinal fasciculus, and the corticospinal tract, by comparing two matched groups of cognitively healthy elderly (n = 21 + 21) with unequal WMH load...
2017: PloS One
https://www.readbyqxmd.com/read/28930599/dissection-of-prodromal-alzheimer-s-disease
#14
Can Sheng, Yue Huang, Ying Han
Pathophysiological changes of Alzheimer's Disease (AD) begin decades before clinical symptoms become apparent, providing an important window for early diagnosis and intervention. Prodromal stage of AD, a great opportunity for effective treatment and postponing the disease onset, has drawn extensive attention. The application of different biomarkers including neuroimaging, biochemical substances and genes makes AD-related pathology detectable in vivo and exploring novel biomarkers with relatively non-invasive and low cost has intrigued a wide range of interests...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28920073/design-of-pilot-studies-to-inform-the-construction-of-composite-outcome-measures
#15
Steven D Edland, M Colin Ard, Weiwei Li, Lingjing Jiang
BACKGROUND: Composite scales have recently been proposed as outcome measures for clinical trials. For example, the Prodromal Alzheimer's Cognitive Composite (PACC) is the sum of z-score normed component measures assessing episodic memory, timed executive function, and global cognition. Alternative methods of calculating composite total scores using the weighted sum of the component measures that maximize signal-to-noise of the resulting composite score have been proposed. Optimal weights can be estimated from pilot data, but it is an open question how large a pilot trial is required to calculate reliably optimal weights...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28916821/reduced-basal-forebrain-atrophy-progression-in-a-randomized-donepezil-trial-in-prodromal-alzheimer-s-disease
#16
Enrica Cavedo, Michel J Grothe, Olivier Colliot, Simone Lista, Marie Chupin, Didier Dormont, Marion Houot, Stephane Lehéricy, Stefan Teipel, Bruno Dubois, Harald Hampel
Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day)...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899422/moderating-effects-of-sex-on-the-impact-of-diagnosis-and-amyloid-positivity-on-verbal-memory-and-hippocampal-volume
#17
Jessica Z K Caldwell, Jody-Lynn Berg, Jeffrey L Cummings, Sarah J Banks
BACKGROUND: Alzheimer's disease (AD) impacts men and women differently, but the effect of sex on predementia stages is unclear. The objective of this study was to examine whether sex moderates the impact of florbetapir positron emission tomography (PET) amyloid positivity (A(+)) on verbal learning and memory performance and hippocampal volume (HV) in normal cognition (NC) and early mild cognitive impairment (eMCI). METHODS: Seven hundred forty-two participants with NC and participants with eMCI from the Alzheimer's Disease Neuroimaging Initiative (second cohort [ADNI2] and Grand Opportunity Cohort [ADNI-GO]) were included...
September 12, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28891447/potential-role-of-neuroimaging-markers-for-early-diagnosis-of-dementia-in-primary-care
#18
Stefan Teipel, Ingo Kilimann, Jochen R Thyrian, Stefan Klöppel, Wolfgang Hoffmann
BACKGROUND: The use of imaging markers for the diagnosis of predementia and early dementia stages of Alzheimer's disease (AD) has widely been explored in research settings and specialized care. The use of these markers in primary care has yet to be established. OBJECTIVE: Summarize current evidence for the usefulness of imaging markers for AD in primary compared to specialized care settings. METHOD: Selective overview of the literature, and pilot data on the use of MRI-based hippocampus and basal forebrain volumetry for the discrimination of AD dementia and mild cognitive impairment (MCI) cases from healthy controls in 58 cases from a primary care cohort and 58 matched cases from a memory clinic's sample...
September 7, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28890916/power-analysis-to-detect-treatment-effects-in-longitudinal-clinical-trials-for-alzheimer-s-disease
#19
Zhiyue Huang, Graciela Muniz-Terrera, Brian D M Tom
INTRODUCTION: Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. METHODS: Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment...
September 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28869465/inflection-point-in-course-of-mild-cognitive-impairment-increased-functional-connectivity-of-default-mode-network
#20
Wuhai Tao, Xin Li, Junying Zhang, Yaojing Chen, Chao Ma, Zhen Liu, Caishui Yang, Wenxiao Wang, Kewei Chen, Jun Wang, Zhanjun Zhang
The alteration of the default mode network (DMN) functional connectivity (FC) has been reported in patients with amnestic mild cognitive impairment (aMCI) as a predictor of Alzheimer's disease (AD). However, no studies exist that examined stage-dependent DMN FC changes throughout the course of aMCI. The present study aims to characterize patterns of DMN FC over three aMCI stages as first defined. Utilizing the extreme groups approach on the performance of memory tasks, aMCI subjects were divided into mild, moderate, and severe stages...
2017: Journal of Alzheimer's Disease: JAD
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