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Background: Neuropsychological assessments are essential to define the cognitive profile and contribute to the diagnosis of Alzheimer’s disease (AD). The progress in knowledge about the pathophysiological process of the disease has allowed conceptualizing AD through biomarkers as a biological continuum that encompasses different clinical stages. Objective: To explore the association between cerebrospinal fluid (CSF) biomarkers of AD and cognition using the NEURONORMA battery, in a sample of cognitively unimpaired (CU), mild cognitive impaired (MCI), and mild dementia of the Alzheimer type (DAT) subjects, and to characterize the cognitive profiles in MCI subjects classified by A/T/N system. Methods: 42 CU, 35 MCI, and 35 mild DAT were assessed using the NEURONORMA battery. Core AD biomarkers [amyloid-β42 (Aβ42) peptide, total tau (t-tau), and phosphorylated tau 181 (p-tau181)] proteins were measured in CSF. Correlation coefficients, multivariate regression, and effect sizes were calculated. We explored the age- and education-adjusted cognitive profiles by A/T/N variants within the MCI group. Results: Cognitive outcomes were directly associated with CSF Aβ42 and inversely with CSF tau measures. We found differences in both biomarkers and cognitive outcomes comparing all pairs except for CSF measures between cognitively impaired groups. The highest effect size was in memory tasks and biomarkers ratios. Lower performances were in memory and executive domains in MCI subjects with AD pathology (A+T+N±) compared to those with normal levels of AD biomarkers (A– T– N). Conclusion: This study provides further evidence of the validity of Spanish NEURONORMA cognitive battery to characterize cognitive impairment in the AD pathological continuum.

We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60–80 years) diagnosed with subjective cognitive decline and APOE ɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer’s disease should be further evaluated.

[Introduction] Limited information is available on people’s experiences of living with Alzheimer’s disease (AD) at earlier stages. This study assessed awareness of diagnosis among people with early-stage AD and its impact on different person-centered outcome measures., [Methods] We conducted an observational, cross-sectional study in 21 memory clinics in Spain. Persons aged 50–90 years, diagnosed with prodromal or mild AD (NIA/AA criteria), a Mini Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5 or 1.0 were recruited. The Representations and Adjustment to Dementia Index (RADIX) was used to assess participants’ beliefs about their condition and its consequences., [Results] A total of 149 persons with early-stage AD were studied. Mean (SD) age was 72.3 (7.0) years and 50.3% were female. Mean duration of AD was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1) and 87.2% had a CDR-GS score of 0.5. Most participants (n = 84, 57.5%) used a descriptive term related to specific AD symptoms (e.g., memory difficulties) when asked what they called their condition. Participants aware of their diagnosis using the term AD (n = 66, 45.2%) were younger, had more depressive symptoms, and poorer life satisfaction and quality of life compared to those without awareness of their specific diagnosis. Practical and emotional consequences RADIX scores showed a significant negative correlation with Quality of Life in Alzheimer’s Disease score (rho = − 0.389 and − 0.413, respectively; p, [Conclusions] Awareness of diagnosis was a common phenomenon in persons with early-stage AD negatively impacting their quality of life. Understanding illness representations in earlier stages may facilitate implementing optimized care that supports improved quality of life and well-being., This study was funded by the Medical Department of Roche Farma Spain (ML42346); funding sources with Life Molecular Imaging, Bioiberica, and Schwabe; and grants from CIBERNED, EU/EFPIA, Instituto de Salud Carlos III (ISCIII), Fundación La Caixa, and Grífols.

[Background] There is a need to better understand the experience of patients living with Alzheimer's disease (AD) in the early stages., [Objective] The aim of the study was to evaluate the perception of quality of life in patients with early-stage AD., [Methods] A multicenter, non-interventional study was conducted including patients of 50–90 years of age with prodromal or mild AD, a Mini-Mental State Examination (MMSE) score ≥22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5.–1.0. The Quality of Life in Alzheimer ’s Disease (QoL-AD) questionnaire was used to assess health-related quality of life. A battery of self-report instruments was used to evaluate different psychological and behavioral domains. Associations between the QoL-AD and other outcome measures were analyzed using Spearman’s rank correlations., [Results] A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years and mean disease duration was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1). The mean QoL-AD score was 37.9 (4.5). Eighty-three percent (n = 124) of patients had moderate-to-severe hopelessness, 22.1% (n = 33) had depressive symptoms, and 36.9% (n = 55) felt stigmatized. The quality of life showed a significant positive correlation with self-efficacy and negative correlations with depression, emotional and practical consequences, stigma, and hopelessness., [Conclusion] Stigma, depressive symptoms, and hopelessness are frequent scenarios in AD negatively impacting quality of life, even in a population with short disease duration and minimal cognitive impairment., This study was funded by the Medical Department of Roche Farma Spain (ML42346).

Data de publicació electrónica: 20-09-2021 Objetivo: ell presente estudio tiene como objetivo proporcionar normas y ajustes para edad, educación y género para el Wisconsin Card Sorting Test (WCST), la Figura Compleja Modificada de Taylor (FCMT) y el Ruff-Light Trail Learning Test (RULIT) como parte del proyecto NEURONORMA-Plus. método: la muestra consiste en 308 individuos cognitivamente sanos de entre 18 y 92 años. Se proporcionan tablas para convertir las puntuaciones brutas en puntuaciones escalares ajustadas por edad y ajustes por educación y género tras aplicar modelos de regresión independientes en 2 grupos de edad (< 50 y ≥ 50 años).Resultados: la edad tuvo un efecto negativo en el rendimiento en ambos grupos etarios. Observamos un efecto positivo de la educación en el rendimiento del WCST en el grupo más joven (< 50 años), y en todas las medidas del FCMT (con la excepción de la tarea de reconocimiento) en el grupo de mayor edad (≥ 50 años). La educación no influyó en el rendimiento en el RULIT, pero sí el género, que tuvo un efecto leve, aunque significativo, mostrando los hombres jóvenes un mayor rendimiento en una variable. conclusión: los datos normativos aportados pueden contribuir en la interpretación clínica del rendimiento en estas pruebas en población española.

Objectives Unilateral spatial neglect (USN) is the incapacity to respond to stimuli presented opposite to a dysfunctional cerebral hemisphere. It is usually caused by non-dominant hemisphere lesions, leads to poorer prognosis and might be underdiagnosed. The objectives of the study were to ascertain the presence of USN in acute stroke patients and analyze the possible degree of underdiagnosis in a Stroke Unit. Materials and methods Prospective study of consecutive non-dominant hemisphere stroke patients within a period of 21 months. "Line Bisection" and "Triangles Cancellation" tests were used for USN screening and "Circle Gap Detection Task" to confirm the USN. The results were compared with routine Stroke Unit assessment using the NIHSS to determine the possible degree of underdiagnosis. Results A total of 62 subjects, 38 women (61.29%), mean age of 74.05 (SD 10.5) years, were included. USN was diagnosed in 25 cases (40.3%) but 56% of them were not detected in routine evaluation using the NIHSS. Conclusions Unilateral spatial neglect, a common cognitive deficit after acute stroke, is greatly underdiagnosed in routine Stroke Unit assessment. The use of simple USN-specific screening tools would improve diagnosis and therefore the possibility of implementing appropriate rehabilitation strategies.

Objective Serial cognitive assessments are useful for many purposes, such as monitoring cognitive decline or evaluating the result of an intervention. In order to determine if an observed change is reliable and meaningful, longitudinal reference data from non-clinical samples are needed. Since neuropsychological outcomes are affected by language and cultural background, cognitive tests should be adapted, and country-based norms collected. The lack of cross-sectional normative data for Spanish population has been partially remediated, but there is still a need of reliable change norms. This paper aims to give an initial response to this need by providing several reliable change indices (RCI) for 1-year follow-up in a Spanish sample. Method A longitudinal observational study was designed. A total of 122 healthy subjects over age 50 were evaluated twice (M = 369.5, SD= 10.7 days) with the NEURONORMA battery. Scores changes were analyzed, and simple discrepancy scores, standard deviation indices, RCI, and standardized regression-based scores were calculated. Results Significant improvements were observed in variables related to memory, both verbal and visual, visuospatial function, and the completion time of complex problems. Reference tables for several RCI are provided for their use in clinical settings. Conclusions Our results confirm the existence of heterogeneous practice effects after 1 year, and support the recommendation of using reliable change norms to avoid misdiagnosis in repeated assessments. This study provides with initial, preliminary norms of cognitive change for its use in Spanish elders. Further studies on larger samples and different inter-visit intervals are still needed.

// Victoria Valls-Comamala 1 , Biuse Guivernau 1 , Jaume Bonet 2 , Marta Puig 1 , Alex Peralvarez-Marin 3 , Ernest Palomer 1 , Xavier Fernandez-Busquets 4, 5 , Xavier Altafaj 6 , Marta Tajes 7 , Albert Puig-Pijoan 8 , Ruben Vicente 1 , Baldomero Oliva 2 and Francisco J. Munoz 1 1 Laboratory of Molecular Physiology, Faculty of Health and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain 2 Laboratory of Structural Bioinformatics (GRIB), Faculty of Health and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain 3 Unitat de Biofisica, Departament de Bioquimica i de Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain 4 Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain 5 ISGlobal, Barcelona Centre for International Health Research, Hospital Clinic-Universitat de Barcelona, Barcelona, Spain 6 Bellvitge Biomedical Research Institute (IDIBELL) - Unit of Neuropharmacology and Pain, University of Barcelona, Barcelona, Spain 7 Heart Diseases Biomedical Research Group, IMIM-Hospital del Mar Medical Research Institute, Barcelona, Spain 8 Servei de Neurologia, Hospital del Mar-IMIM-Parc de Salut Mar, Barcelona, Spain Correspondence to: Francisco J. Munoz, email: paco.munoz@upf.edu Keywords: Alzheimer’s disease, amyloid, immunoglobulin, Fab, oligomers Received: December 22, 2016 Accepted: March 22, 2017 Published: April 13, 2017 ABSTRACT The amyloid beta-peptide (Aβ) plays a leading role in Alzheimer’s disease (AD) physiopathology. Even though monomeric forms of Aβ are harmless to cells, Aβ can aggregate into β-sheet oligomers and fibrils, which are both neurotoxic. Therefore, one of the main therapeutic approaches to cure or delay AD onset and progression is targeting Aβ aggregation. In the present study, we show that a pool of human gamma immunoglobulins (IgG) protected cortical neurons from the challenge with Aβ oligomers, as assayed by MTT reduction, caspase-3 activation and cytoskeleton integrity. In addition, we report the inhibitory effect of IgG on Aβ aggregation, as shown by Thioflavin T assay, size exclusion chromatography and atomic force microscopy. Similar results were obtained with Palivizumab, a human anti-sincitial virus antibody. In order to dissect the important domains, we cleaved the pool of human IgG with papain to obtain Fab and Fc fragments. Using these cleaved fragments, we functionally identified Fab as the immunoglobulin fragment inhibiting Aβ aggregation, a result that was further confirmed by an in silico structural model. Interestingly, bioinformatic tools show a highly conserved structure able to bind amyloid in the Fab region. Overall, our data strongly support the inhibitory effect of human IgG on Aβ aggregation and its neuroprotective role.

Introduction: the current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. Methods: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. Results: the (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. Discussion: this is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD. This manuscript was facilitated by the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART), through the Biofluid Based Biomarkers Professional Interest Area (BBB-PIA). The views and opinions expressed in this publication represent those of the authors and do not necessarily reflect those of the BBB-PIA membership, ISTAART, or the Alzheimer's Association. The authors thank the French Society of Clinical Biology, the ISTAART BBB-PIA, and the Society for Neurochemistry and Clinical CSF analysis for their help in initiating this work. Constance Delaby received no support for the present manuscript. Charlotte Teunissen received the following grants during the last 36 months: Research of CET is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 [MIRIADE], and JPND), Health Holland, the Dutch Research Council (ZonMw), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association. CT and WF are recipients of ABOARD, which is a public-private partnership receiving funding from ZonMw (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. IV is appointed on a research grant by Alzheimer Nederland (NL-17004). She received no support for the present manuscript. Kaj Blennow is supported by the Swedish Alzheimer Foundation (#AF-742881) and Hjärnfonden, Sweden (#FO2017-0243). He received no support for the present manuscript. Daniel Alcolea received funding from Institute of Health Carlos III (ISCIII), Spain PI18/00435 and INT19/00016, and by the Department of Health Generalitat de Catalunya PERIS program SLT006/17/125. He received no support for the present manuscript. Ivan Arisi was partly supported by: Fondo Ordinario Enti (FOE D.M 865/2019) funds in the framework of a collaboration agreement between the Italian National Research Council and EBRI (2019-2021); POR (Operative Program Lazio Region, Italy) FESR (European Program Regional Development) 2014-2020, Public Notice “LIFE 2020” MODIAG Project. Elodie Bouaziz-Amar received no support for the present manuscript. Anne Beaume received no support for the present manuscript. Aurélie Bedel received no support for the present manuscript. Giovanni Bellomo is supported by University of Perugia, CIRMMP, IRST Istituto Romagnolo per lo Studio e la Cura dei Tumori, Innuvatech srl. He received no support for the present manuscript. Edith Bigot-Corbel received no support for the present manuscript. Maria Bjerke received no support for the present manuscript. Marie-Céline Blanc-Quintin received no support for the present manuscript. Mercè Boada received support from LA CAIXA, IMI, ISCIII H2020 the European Union/EFPIA Innovative Medicines Initiative Joint Undertaking MOPEAD project (Grants No. 115985) and is also supported by national grant, PI17/01474 from Acción Estratégica en Salud, integrated into the Spanish National Plan of R+D+I and founded by ISCIII (Instituto de Salud Carlos III)-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER- “Una manera de Hacer Europa”). She received no support for the present manuscript. Olivier Bousigues is supported by A2MCL Alsace Alzheimer. He received no support for the present manuscript. Miles D. Chapman received no support for the present manuscript. Mari L. DeMarco is supported by the Michael Smith Foundation for Health Research, Brain Canada (Canada Brain Research Fund), Health Canada, Women's Brain Health Initiative, Alzheimer Society of Canada, St. Paul's Foundation, Djavad Mowafaghian Centre for Brain Health at the University of British Columbia and the Canadian Consortium for Neurodegeneration and Aging; with all funds provided to the University of British Columbia. Mara D'Onofrio was partly supported by Fondo Ordinario Enti (FOE D.M 865/2019) funds in the framework of a collaboration agreement between the Italian National Research Council POR (Operative Program Lazio Region, Italy) FESR (European Program Regional Development) 2014-2020, Public Notice “LIFE 2020″, MODIAG Project. She received no support for the present manuscript. Julien Dumurgier received no support for the present manuscript. Diane Dufour received no support for the present manuscript. Sebastiaan Engelborghs is supported for various projects: Research Project GSKE/FMRE, Research Project FWO Vlaanderen, PhD fellowship FWO Vlaanderen (n = 3), VLAIO PhD fellowship. He received no support for the present manuscript. Hermann Esselmann received no support for the present manuscript. Anne Fogli received no support for the present manuscript. Audrey Gabelle received no support for the present manuscript. Elisabetta Galloni received no support for the present manuscript. Clémentine Gondolf received no support for the present manuscript. Frédérique Grandhomme received no support for the present manuscript. Oriol Grau-Rivera receives grants from the Spanish Ministry of Science, Innovation and Universities (FJCI-2017-33437), and from the Alzheimer's Association Research Fellowship Program (2019-AARF-644568). He received no support for the present manuscript. Melanie Hart receives UCLH Biomedical Research Centre support from NIHR (Neurosciences). She received no support for the present manuscript. Takeshi Ikeuchi received the following grants to his institution AMED: 21dk0207049, 21dk0207045, 21ek0109545, 20ek0109350, 20ek0109392. He received no support for the present manuscript. Andreas Jeromin received no support for the present manuscript. Kensaku Kasuga received no support for the present manuscript. Ashvini Keshavan is supported by the Weston Brain Institute/Selfridges Foundation grant UB170045. She received no support for the present manuscript. Michael Khalil received unrestricted research grants from Biogen and Novartis. He received no support for the present manuscript. Peter Körtvelyessy received no support for the present manuscript. Agnieszka Kulczynska-Przybik received no support for the present manuscript. Jean-Louis Laplanche received no support for the present manuscript. Qiao-Xin Li received no support for the present manuscript. Alberto Lleó is supported by grants from Generalitat de Catalunya (PERIS SLT002/16/00408), Instituto de Salud Carlos III (PI17/01896), Instituto de Salud Carlos III CIBERNED. He received no support for the present manuscript. Catherine Malaplate received no support for the present manuscript. Marta Marquié is supported by the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa) grant PI19/00335. She received no support for the present manuscript. Colin M. Masters received no support for the present manuscript. Barbara Mroczko received a grant from The Binding Site Group and Biokom Diagnostyka. She received no support for the present manuscript. Léonor Nogueira received no support for the present manuscript. Adelina Orellana received no support for the present manuscript. Markus Otto is supported by BMBF, Thierry Latran foundation, EU, DFG. He received no support for the present manuscript. Jean-Baptiste Oudart is supported by Astrazeneca grant for a research program on EGFR targeted therapy resistance in NSCLC. He received no support for the present manuscript. Claire Paquet received no support for the present manuscript. Federico Paolini received no support for the present manuscript. Lucilla Parnetti received no support for the present manuscript. Armand Perret-Liaudet received no support for the present manuscript. Katell Peoc'h is supported by contract with Siemens Healthineers. She received no support for the present manuscript. Koen Poesen received no support for the present manuscript. Albert Puig-Pijoan received no support for the present manuscript. Isabelle Quadrio received no support for the present manuscript. Murielle Quillard-Muraine received no support for the present manuscript. Benoît Rucheton received no support for the present manuscript. Susanne Schraen received no support for the present manuscript. Jonathan M. Schott is supported by the Medical Research Council, Alzheimer's Research UK, Weston Brain Institute, British Heart Foundation, Alzheimer's Association. He received no support for the present manuscript. Leslie M. Shaw is supported by NIA for ADNI Biomarker Core, UPENN ADRC Biomarker Corr, MJ Fox PPMI for CSF Biomarker measurements, Roche for IIS study of AD biomarkers. He received no support for the present manuscript. Marc Suárez-Calvet receives funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 948677). He also receives funding from the Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). He received no support for the present manuscript. Magda Tsolaki received no support for the present manuscript. Hayrettin Tumani is supported by Alexion, Bayer, Biogen, Celgene, Genzyme-Sanofi, Merck, Novartis, Roche, Teva. He received no support for the present manuscript. Chinedu T Udeh-Momoh is supported by Alzheimer research UK (Project Grant). He received no support for the present manuscript. Lucie Vaudran received no support for the present manuscript. Marcel M. Verbeek is supported by the BIONIC project (no. 733050822, which has been made possible by ZonMw within the framework of “Memorabel,” the research and innovation program for dementia, as part of the Dutch national “Deltaplan for Dementia”: zonmw.nl/dementiaresearch), and the CAFÉ project (the National Institutes of Health, USA, grant number 5R01NS104147-02). The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and University of Rhode Island University. MM Verbeek is also supported by a grant from the Selfridges Group Foundation. He received no support for the present manuscript. Federico Verde received no support for the present manuscript. Lisa Vermunt is supported by Alzheimer Nederland. She received no support for the present manuscript. Jonathan Volgesgang is supported by Clinician Scientist Research Fellowship, German Research Foundation (Deutsche Forschungsgesellschaft, project number: 413501650; 09/01/2019-02/28/2021); Eric Dorris Memorial Fellowship (McLean Hospital; 07/01/2020-06/30/2021). He received no support for the present manuscript. Jens Wiltfang is supported by Federal Ministry of Education and Research (BMBF) State of Lower Saxony; He received no support for the present manuscript. Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL. He received no support for the present manuscript. Sylvain Lehmann received no support for the present manuscript.