Performance on the RI-48 Cued Recall Test Best Predicts Conversion to Dementia at the 5- and 10-Year Follow-Ups

TheRI-48 cued recall test was devised to discriminate between healthy elderly and patients with mild cognitive impairment who are at risk of developing Alzheimer's disease (AD). However, no long-term follow-up studies have been conducted using this test

The elusive tau molecular structures: can we translate the recent breakthroughs into new targets for intervention?

Insights into tau molecular structures have advanced significantly in recent years. This field has been the subject of recent breakthroughs, including the first cryo-electron microscopy structures of tau filaments from Alzheimer’s and Pick’s disease inclusions, as well as the structure of the repeat regions of tau bound to microtubules. Tau structure covers various species as the tau protein itself takes many forms. We will here address a range of studies that help to define the many facets of tau protein structures and how they translate into pathogenic forms. New results shed light on previous data that need now to be revisited in order to up-date our knowledge of tau molecular structure. Finally, we explore how these data can contribute the important medical aspects of this research - diagnosis and therapeutics

Unmasking selective path integration deficits inAlzheimer’s disease risk carriers

Alzheimer’s disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE4-carriers during a virtual navigation task. We report a selective impairment in APOE4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset

A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

OBJECTIVE: To elaborate a new algorithm to establish a standardized method to define cuff-offs for CSF biomarkers of Alzheimer's disease (AD) by validating the algorithm against CSF classification derived from PET imaging. METHODS: Low and high levels of CSF phosphorylated tau were first identified to establish optimal cut-offs for CSF amyloid-β peptide (Aβ) biomarkers. These Aβ cut-offs were then used to determine cut-offs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. RESULTS: A total of 6,922 subjects with CSF biomarkers data were included (mean (SD) age: 70.6 (8.5) years, 51.0% women). In the ADNI study population (n=497), the agreement between classification based on our algorithm and one based on amyloid/tau PET imaging was high with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n=6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. DISCUSSION: The proposed novel, pragmatic method to determine CSF biomarkers cut-offs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification

Pengaruh Brand Trust dan Brand Equity terhadap Loyalitas Konsumen pada Produk Kosmetik Wardah (Survey Konsumen pada PT. Paragon Technology And Innovation Cabang Pekanbaru)

The purpose of this study was to determine the influence of brand trust ( X1 ) and brand equity ( X2 ) customer loyalty ( Y ) in cosmetic products Wardah ( consumer survey on PT . Paragon technology and innovation branches pekanbaru ) . The method in this research is quantitatively using SPSS 21 program , where samples were used that consumers using cosmetic products Wardah by respondents as many as 100 people sampling technique is accidental sampling using the formula slovin . The results showed that the test results simultaneously obtained from the F count was 34.888 while the value of F table 3.090 . This means that F count> F table and significant value 0,000 < alpha of 0.05 . This means that brand trust and brand equity simultaneously significant effect on consumer loyalty to cosmetic products Wardah

Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment:A European Alzheimer's Disease Consortium survey

Objectives: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. Methods: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. Results: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. Conclusions: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning

On episodic memory encoding in patients with mild cognitive impairment : a cognitive and imaging approach

AD research has progressed considerably over the past twenty years. We have moved from observation of a clinical dementia syndrome and description of pathological brain lesions at autopsy, to more precise characterization of the memory deficits predictive of AD dementia and the ability to confirm the diagnosis of AD using biological and brain imaging markers. In this work, the concept of MCI has emerged to define non-demented patients suffering from memory deficits and at high risk of evolving to AD dementia. The present thesis has addressed several issues related to the cognitive and imaging assessment of MCI patients. In addition to improving diagnostic accuracy, one of our main goals was to understand the mechanisms linking cognitive symptoms to neural damage. We showed that associative encoding was decreased in MCI, and that sensitivity to interference was increased. Anterior hippocampus dysfunction, and more precisely CA3 subfield atrophy, may account for both phenomena. The mechanisms involved could include a pattern separation deficit, although this needs to be confirmed by further studies. Improved cognitive assessment and brain imaging techniques have advanced AD research; but at the same time, these improvements have made AD research and clinical practice more complex. There are now many different ways to approach AD, each with their own strengths and weaknesses, most of them complementary. AD research now requires many different competencies (engineering, computer science, brain imaging, neuroanatomy, neuropathology, neuropsychology, empathy…), reinforcing the need for collaborations among experts from different fields in order to meet the challenges of tomorrow…La recherche sur le diagnostic précoce de la maladie d’Alzheimer a considérablement progressé au cours des vingt dernières années. Dans les années quatre-vingt, nous ne pouvions qu’observer cliniquement un syndrome démentiel et décrire les lésions cérébrales typiques de la maladie d’Alzheimer à l’autopsie. De nos jours, certains troubles de la mémoire prédictifs d’une évolution vers la démence Alzheimer ont pu être identifiés. La présence de ces altérations cognitives spécifiques couplée à des marqueurs biologiques et à l’imagerie cérébrale permet de diagnostiquer la maladie dans son stade pré-démentiel, soit jusqu’à dix ans avant l’apparition de la démence. Dans ce travail de caractérisation, le concept de patient présentant des troubles cognitifs légers (« mild cognitive impairment » dans la littérature anglo-saxonne) a émergé pour définir des patients non déments souffrant de déficits mnésiques. Ces patients se sont avérés à haut risque d’évoluer vers une démence d’Alzheimer. Cette thèse aborde plusieurs questions liées à l’évaluation cognitive et à l’imagerie cérébrale des patients présentant des troubles cognitifs légers. Outre l’amélioration de notre capacité diagnostique, l'un des principaux objectifs de cette thèse est de mieux comprendre les mécanismes qui lient symptômes cognitifs et dommages neuronaux. Nous montrons que l'encodage associatif est diminué chez les patients souffrant de troubles cognitifs légers, et que leur sensibilité à l’interférence est augmentée. La dysfonction de l’hippocampe antérieur, et plus précisément l’atrophie du sous-champ hippocampique CA3, peut rendre compte de ces deux déficits cognitifs. Les mécanismes impliqués pourraient inclure un déficit de séparation de pattern, même si cette hypothèse nécessiterait confirmation. L’amélioration des techniques d'évaluation cognitive et d'imagerie cérébrale ont permis à la recherche de progresser, mais dans le même temps, ces avancées ont rendus plus complexes la recherche et la pratique clinique. Il existe maintenant de nombreuses manières différentes d'aborder la maladie d’Alzheimer, chacune présentant ses propres forces et faiblesses ; la plupart de ces approches sont néanmoins complémentaires. La recherche sur la maladie d’Alzheimer exige aujourd’hui de nombreuses compétences différentes (en ingénierie informatique, en imagerie cérébrale, en neuroanatomie, neuropathologie, neuropsychologie, ainsi qu’une bonne dose d'empathie ...) Ceci renforçe la nécessité de collaboration entre experts de champs différents afin de relever les défis de demain ...(MED 3) -- UCL, 201

Dépister et prévenir la maladie d’Alzheimer avant les pertes de mémoire : actualités et perspectives

La recherche clinique sur les phases précliniques de la maladie d’Alzheimer est en pleine expansion. Le développement récent de marqueurs permettant de mesurer in vivo la pathologie Alzheimer a ouvert la voie à (1) une recherche visant à comprendre les liens entre pathologie et déclin cognitif; (2) la mise en place d’essais cliniques préventifs. Outre l’autopsie cérébrale, nous disposons aujourd’hui d’analyses du liquide céphalo-rachidien et de radiotraceurs spécifiques des protéines tau et amyloïde. La prochaine décennie s’annonce riche en découvertes avec le raffinement des traceurs tau, des cibles thérapeutiques et de notre compréhension des processus biologiques impliqués dans la maladie

Utilisation de la TEP-amyloïde pour prédire l’évolution à long terme des patients non déments consultant à la Clinique de la Mémoire : intérêt de la quantification Centiloïde, une échelle internationale standardisée

L’objective de ce travail est d’établir la valeur de la tomographie par émissions de positons avec traceur de la plaque amyloïde pour prédire l’évolution à long terme vers la démence de patients non déments consultant à la Clinique de la Mémoire.[Defining a Centiloid Scale threshold predicting long-term progression to dementia in patients attending the Memory Clinic: An [18F]-Flutemetamol amyloid-PET study] The objective of this work is to establish the value of amyloid imaging using positron emission tomography to predict the long-term progression towards dementia of non-demented patients attending Memory Clinics

Preclinical Alzheimer’s disease: how to predict who will decline next year?

This scientific commentary refers to 'Medial temporal tau predicts memory decline in cognitively unimpaired elderly', by Kwan et al