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In 2024, therapeutic and diagnostic advancements are shaping the field of neurology. Three new drugs show promise for treating myasthenia gravis and chronic inflammatory demyelinating polyneuropathy. A new classification for Parkinson's disease has been proposed, while a neuroprosthesis is improving gait in advanced stages. Revised criteria for inclusion body myositis and multiple sclerosis are refining diagnoses, and blood biomarkers are enabling early detection of Alzheimer's disease. The effectiveness of early thrombolysis in stroke has been confirmed, and new treatments are being explored for cerebral hemorrhages. In epilepsy, surgery reduces mortality by 30% in drug-resistant patients. Finally, new treatments targeting PACAP and CGRP are reducing refractory migraines with good tolerability., Competing Interests: le CHUV a reçu pour M. Théaudin : des honoraires de conférencière, des frais pour participation à des comités consultatifs et des subventions de voyage de la part d’Alexion, Argenx, Sanofi, Biogen, Roche, Novartis, CSL Behring, Merck, Alnylam et AstraZeneca. P. Ryvlin a perçu des honoraires des laboratoires Novartis, Lundbeck et Angelini Pharma dans le cadre de présentations orales et de comités consultatifs, ainsi qu’une subvention de recherche du laboratoire Novartis. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction: The possible authorisation of new monoclonal antibody therapies for Alzheimer's disease poses challenges for healthcare systems worldwide. In this paper, the Swiss Memory Clinics association (SMC) analyses the available resources and identifies potential health care shortages. Overcoming potential bottlenecks is a challenge that requires action at various levels. However, our analysis also shows that we are well positioned in Switzerland to integrate new developments into existing care structures., Competing Interests: Die Autorinnen und Autoren dieser Publikation haben alle relevanten Informationen über mögliche Interessenkonflikte offengelegt. Sollten Sie weitere Informationen wünschen, wenden Sie sich bitte an die Geschäftsstelle unter: info@swissmemoryclinics.ch., (© 2024 Aerzteverlag medinfo AG.)

Background: Tight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes., Methods: Retrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated., Results: Among 161 patients included (median age 76.8 years, range 60.8-93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj β coeff: -0.217, 95%CI: [-0.416 to -0.018], p = .033), the precentral gyri (adj βcoeff:-0.277, 95%CI: [-0.482 to -0.073], p = .009), the superior frontal gyri (adj βcoeff: -0.244, 95%CI: [-0.458 to -0.030], p = .026), the calcarine cortex (adj βcoeff:-0.193, 95%CI: [-0.386 to -0.001], p = .049), the superior occipital gyri (adj βcoeff: -0.291, 95%CI: [-0.521 to -0.061], p = .014) and the inferior occipital gyri (adj βcoeff: -0.236, 95%CI: [-0.456 to - 0.015], p = .036)., Conclusion: A significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample., (© 2024. The Author(s).)

The year 2023 is marked by the arrival on the market of lecanemab for the treatment of Alzheimer's disease. New biomarkers have demonstrated their usefulness in monitoring peripheral neuropathies and diagnosing synucleinopathies. A genetic study has highlighted the role of nervous system cells in the risk of progression of multiple sclerosis (MS). The adverse effects of anticonvulsant treatments after prenatal exposure and on lipid metabolism have been clarified. New anti-CGRP treatments have demonstrated their efficacy in migraine attacks and chronic migraines. The criteria for thrombectomy have been further broadened. And finally, rehabilitation is refining the management of cerebrovascular patients and those with secondary progressive MS., Competing Interests: La Dre M. Théaudin a reçu des subventions de voyage et des honoraires de conférencière et de conseil de la part d’Alnylam, Sobi, Merck, Sanofi, Novartis et Biogen. Le Pr P. Ryvlin a reçu des honoraires de conférencier et de conseil de la part de Novartis, Eli-Lilly et Lundbeck. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Alzheimer's disease (AD) is emerging as a significant public health challenge in Africa, with predictions indicating a tripling in incidence by 2050. The diagnosis of AD on the African continent is notably difficult, leading to late detection that severely limits treatment options and significantly impacts the quality of life for patients and their families., Summary: This review focuses on the potential of high-sensitivity specific blood biomarkers as promising tools for improving AD diagnosis and management globally, particularly in Africa. These advances are particularly pertinent in the continent, where access to medical and technical resources is often limited., Key Messages: Identifying precise, sensitive, and specific blood biomarkers could contribute to the biological characterization and management of AD in Africa. Such advances promise to improve patient care and pave the way for new regional opportunities in pharmaceutical research and drug trials on the continent for AD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Amnestic syndrome of the hippocampal type (ASHT) in Memory Clinics is a presentation common to Alzheimer's disease (AD). However, ASHT can be found in other neurodegenerative disorders., Objective: To compare brain morphometry including hippocampal volumes between amnestic older adults with and without AD pathology and investigate their relationship with memory performance and cerebrospinal fluid (CSF) biomarkers., Methods: Brain morphometry of 92 consecutive patients (72.5±6.8 years old; 39% female) with Free and Cued Selective Recall Reminding Test (FCSRT) total recall < 40/48 was assessed with an automated algorithm and compared between AD and non-AD patients, as defined by CSF biomarkers., Results: AD and non-AD patients presented comparable brain morphology. Total recall was associated to hippocampal volume irrespectively from AD pathology., Conclusions: Brain morphometry, including hippocampal volumes, is similar between AD and non-AD older adults with ASHT evaluated in a Memory Clinic, underlying the importance of using molecular biomarkers for the diagnosis of AD.

Introduction: The risk of developing Alzheimer's disease (AD) in older adults increasingly is being discussed in the literature on Post-Acute COVID-19 Syndrome (PACS). Remote digital Assessments for Preclinical AD (RAPAs) are becoming more important in screening for early AD, and should always be available for PACS patients, especially for patients at risk of AD. This systematic review examines the potential for using RAPA to identify impairments in PACS patients, scrutinizes the supporting evidence, and describes the recommendations of experts regarding their use., Methods: We conducted a thorough search using the PubMed and Embase databases. Systematic reviews (with or without meta-analysis), narrative reviews, and observational studies that assessed patients with PACS on specific RAPAs were included. The RAPAs that were identified looked for impairments in olfactory, eye-tracking, graphical, speech and language, central auditory, or spatial navigation abilities. The recommendations' final grades were determined by evaluating the strength of the evidence and by having a consensus discussion about the results of the Delphi rounds among an international Delphi consensus panel called IMPACT, sponsored by the French National Research Agency. The consensus panel included 11 international experts from France, Switzerland, and Canada., Results: Based on the available evidence, olfaction is the most long-lasting impairment found in PACS patients. However, while olfaction is the most prevalent impairment, expert consensus statements recommend that AD olfactory screening should not be used on patients with a history of PACS at this point in time. Experts recommend that olfactory screenings can only be recommended once those under study have reported full recovery. This is particularly important for the deployment of the olfactory identification subdimension. The expert assessment that more long-term studies are needed after a period of full recovery, suggests that this consensus statement requires an update in a few years., Conclusion: Based on available evidence, olfaction could be long-lasting in PACS patients. However, according to expert consensus statements, AD olfactory screening is not recommended for patients with a history of PACS until complete recovery has been confirmed in the literature, particularly for the identification sub-dimension. This consensus statement may require an update in a few years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vandersteen, Plonka, Manera, Sawchuk, Lafontaine, Galery, Rouaud, Bengaied, Launay, Guérin, Robert, Allali, Beauchet and Gros.)

Neurocognitive disorders (TNC) are of a public health concern. An early and accurate diagnosis is important to tailor a personalised care. We illustrate the importance of a graduated etiological diagnostic approach centered on the clinical presentation employing the case of a patient with a progressive neurovisual disorder suggestive of a common form of Alzheimer's disease. The results of the CSF biomarkers analysis argue against this diagnosis and justifies seeking a Lewy body disease as a differential diagnosis even if all the clinical criteria are initially incomplete. In this article, we illustrate the progressive and graduated approach in the use of complementary medical tests available for reliable and early diagnosis in order to optimise the care plan and predict clinical progress and needs., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction: Dopaminergic scintigraphic imaging is a cornerstone to support the diagnosis in dementia with Lewy bodies. To clarify the current state of knowledge on this imaging modality and its impact on clinical diagnosis, we performed an updated systematic review of the literature., Methods: This systematic review was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through June 2022 was performed using the following search algorithm: (a) "Lewy body" [TI] OR "Lewy bodies" [TI] and (b) ("DaTscan" OR "ioflupane" OR "123ip" OR "123?ip" OR "123 ip" OR "123i-FP-CIT" OR "FPCIT" OR "FP-CIT" OR "beta?CIT" OR "beta CIT" OR "CIT?SPECT" OR "CIT SPECT" OR "Dat?scan*" OR "dat scan*" OR "dat?spect*" OR "SPECT"). Risk of bias and applicability concerns of the studies were evaluated using the QUADAS-2 tool., Results: We performed a qualitative analysis of 59 studies. Of the 59 studies, 19 (32%) addressed the diagnostic performance of dopamine transporter imaging, 15 (25%) assessed the identification of dementia with Lewy bodies in the spectrum of Lewy body disease and 18 (31%) investigated the role of functional dopaminergic imaging in distinguishing dementia with Lewy bodies from other dementias. Dopamine transporter loss was correlated with clinical outcomes in 19 studies (32%) and with other functional imaging modalities in 15 studies (25%). Heterogeneous technical aspects were found among the studies through the use of various radioligands, the more prevalent being the [123I]N‑ω‑fluoropropyl‑2β‑carbomethoxy‑3β‑(4‑iodophenyl) nortropane ( 123 I-FP-CIT) in 54 studies (91.5%). Image analysis used visual analysis (9 studies, 15%), semi-quantitative analysis (29 studies, 49%), or a combination of both (16 studies, 27%)., Conclusion: Our systematic review confirms the major role of dopaminergic scintigraphic imaging in the assessment of dementia with Lewy bodies. Early diagnosis could be facilitated by identifying the prodromes of dementia with Lewy bodies using dopaminergic scintigraphic imaging coupled with emphasis on clinical neuropsychiatric symptoms. Most published studies use a semi-quantitative analytical assessment of tracer uptake, while there are no studies using quantitative analytical methods to measure dopamine transporter loss. The superiority of a purely quantitative approach to assess dopaminergic transmission more accurately needs to be further clarified., (© 2023. The Author(s).)

In most soft wheat products such as cakes, baking powder (BP) plays an important role in achieving the desired product volume through batter aeration by the release of CO 2 during baking. However, the optimization of a blend of constituents in BP is minimally documented, especially the selection of acids, which is often supported by the suppliers based on their experience. The objective of this study was to evaluate the impact of two sodium acid pyrophosphate leavening acids (SAPP10 and SAPP40) at different levels in BP on final pound cake properties. A central composite design of the response surface methodology (RSM) was used to design the blend ratio of SAPP with different amounts of BP to investigate some selected cake parameters such as specific volume and conformation. Results showed that increasing the BP level significantly increased the batter specific volume and porosity but dropped as BP approached maximum (4.52%). The batter pH was influenced by SAPP type; SAPP40 presented a relatively sufficient neutralization of the leaving system as compared to SAPP10. Furthermore, lower BP levels resulted in cakes with large air cells, which presented a non-homogeneous crumb grain. This study therefore highlights the need to identify the optimum amount of BP to attain the desired product qualities.

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion. The causal relationship between Epstein-Barr infection and multiple sclerosis has been proved thanks to a large cohort study. A new possibility of subcutaneous continuous levodopa administration gave promising result. Finally, numerous studies confirmed the efficacy and excellent tolerability of anti-CGRP antibodies., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Syphilis is a sexually transmitted disease which incidence increased over the last 10 years in Switzerland. The clinical and neurocognitive manifestations observed in case of symptomatic neurosyphilis can be very heterogeneous and can mimic neurocognitive disorders of other origins. This article discusses the diagnostic and management pitfalls in an older patient whose diagnosis of neurosyphilis was initially suspected during a home visit., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Cerebellar ataxia can be caused by neoplasia, toxics (drugs, heavy metals, alcohol), infection, vascular lesions or auto-immune and paraneoplastic pathologies. Neuroimaging must be performed urgently in case of sudden onset and serologies as well as a lumbar puncture should be performed. Several case reports of ataxia associated with COVID-19 have been published, however the underlying pathogenic mechanisms remain unclear. This is a diagnosis of exclusion when other causes are ruled out and when the ataxia appears simultaneously to COVID-19 infection. We lack data on best management, but the prognosis appears mostly favorable with good functional recovery without any specific treatment. This paper describes the case of a patient who developed a cerebellar ataxia as the only neurological manifestation of a SARS-CoV-2 infection., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate diffusion-weighted imaging lesions (HPDL). The literature suggests that TGA may present with unusual features. This study analyses atypical clinical and radiological manifestations of patients with TGA and/or HPDL., Methods: We retrospectively reviewed patients with atypical clinical or radiological presentations of TGA and/or HPDL in three neurology centers. We also performed a systematic review of literature using predefined search terms. Results were classified as: A) Atypical clinical manifestations of TGA (such as amnesia with additional manifestations, or only non-amnesic manifestations); B) Atypical radiological manifestations of clinically typical TGA., Results: We identified 83 patients: 18 in our centres (median age 63.5 years, 39% female) and 65 in the literature. In group A, 43 patients presented atypical clinical manifestations such as TGA with added transitory cognitive or sensory-motor deficits, seizures, headaches, but also non-amnesic presentations associated with HPDL and incidental HPDL without symptoms. In group B, 40 patients with typical clinical TGA showed extra-hippocampal punctate diffusion lesions (E-HPDL) which disappeared on follow-up imaging. Using clinical and radiological manifestations, we classified these patients into different categories describing a "TGA-PDL spectrum"., Conclusions: TGA may have atypical clinical manifestations despite typical neuroimaging and patients with typical TGA may show vanishing extra-hippocampal punctate diffusion lesions. TGA, related clinical manifestations, and vanishing punctate diffusion lesions should be considered part of a larger "TGA-PDL spectrum", allowing for better diagnosis of typical and atypical cases and stimulating further studies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate lesions on diffusion-weighted imaging (hippocampal punctate diffusion lesion, HPDL). The recent literature suggests that TGA may be triggered by acute neurological conditions., Objective: To study patients with TGA triggered by an acute neurological disease., Methods: We retrospectively reviewed patients from two neurology centres with TGA (with or without HPDL) in whom an acute neurological condition could be identified as trigger. We also performed a systematic review of the literature of this situation using predefined search terms., Results: We identified 38 patients (median age 62 years, 55.3% female): 6 from our centres and 32 from the literature. Acute neurovascular diseases that preceded or were associated with TGA included ischemic and haemorrhagic strokes, convexity subarachnoid haemorrhage, and reversible cerebral vasoconstriction syndrome. As non-vascular acute neurological diseases, we identified migraine and peripheral-origin vertigo. The clinical manifestation of the neurological trigger showed a variable temporal relation with TGA onset; in some cases preceding and in others co-occurring with TGA manifestation. In some cases, presumed neurological triggers were asymptomatic and diagnosed from the neuroimaging done for the TGA., Conclusions: Acute vascular and non-vascular neurological events may trigger TGAs or may occur simultaneously. In the first case, such an acute neurological disease may activate direct pathways within the nervous systems leading to TGA, or alternatively elicit a bodily sympathetic overactivity cascade. In the second case, both neurological events may be the result of a common external stressor., (© 2022. Fondazione Società Italiana di Neurologia.)

In 2021, we assisted to the publication of new diagnostic criteria, classifications, and guidelines (CIDP, brain tumors, auto-immune encephalitis). Several studies helped to define the pharmacological management of focal and generalized epileptic seizures and epilepsy in pregnant women. The availability of biomarkers and the approval of immunotherapies are modifying the landscape of dementia management. Endovascular interventions without previous thrombolysis seems to be effective in anterior circulation acute ischemic stroke (AIS) and severe posterior circulation AIS. Neurologic complications of Sars-CoV-2 infection were further studied, as well as the efficacy of vaccines in immunosuppressed patients. New molecules and techniques show promising results for the treatment of migraine and cluster headache., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

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., (© 2020 John Wiley & Sons Ltd.)

Cognitive impairment can interfere with the fitness to drive. An increase in requests to assess this aspect is observed at Leenaards Memory Centre. Changes in the law could be an explanatory factor. The views formulated in 2019 are mainly unfavorable because all the patients present cognitive disorders, generally attributed to Alzheimer's disease or a related disorder, but never linked with aging only. Moreover, unfavorable views are frequently expressed before the age of 75. Therefore, each patient is unique, and each decision is based neither on the patient's age or his diagnosis, but rather on his cognitive profile. In this article we discuss the reasons for an unfavorable view and discuss them in the context of the tasks of our centre., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Significant developments were published in 2020 in the field of blood biomarkers in Alzheimer's disease. Several studies helped to define more accurately the management of status epilepticus and of epilepsy in women of childbearing age. The new Swiss guidelines for the pre-hospital management of acute stroke were issued, as are new targets for stroke prevention. Numerous advances concerning the management of NMO-SD (NeuroMyelitis Optica Spectrum Disorder) were published. Different neurological presentations linked to the COVID-19 pandemic were described (central and peripheral). Several studies confirmed the effectiveness of new migraine treatments (including anti-CGRP). New pharmacological therapies are available for Parkinson's disease., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: The frontal variant of Alzheimer's disease (fAD) is poorly understood and poorly defined. The diagnosis remains challenging. The main differential diagnosis is the behavioral variant of frontotemporal degeneration (bvFTD). For fAD, there is some dissociation between the clinical frontal presentation and imaging and neuropathological studies, which do not always find a specific involvement of the frontal lobes. DAPHNE is a behavioral scale, which demonstrated excellent performance to distinguish between bvFTD and AD., Objective: The aim of the present study was to assess the reliability of this new tool to improve the clinical diagnosis of fAD., Methods: Twenty fAD patients and their caregivers were prospectively included and were compared with 36 bvFTD and 22 AD patients., Results: The three main behavioral disorders in the fAD patients were apathy, loss of empathy, and disinhibition. Three disorders were discriminant because they were less frequent and less severe in the fAD patients than in the bvFTD patients, namely hyperorality, neglect, and perseverations. This specific pattern of behavioral disorders was corroborated by SPECT or 18FDG PET-CT scan that showed that patients with fAD could have a medial frontal hypoperfusion, whereas in bvFTD patients the orbitofrontal cortex was the main involved region, with more diffuse hypoperfusion., Conclusion: We demonstrated that DAPHNE had good sensitivity and good specificity to discriminate between the three groups and in particular between fAD and bvFTD patients. DAPHNE is a quick tool that could help clinicians in memory clinics not only to differentiate bvFTD from typical AD but also from fAD.

Chemotherapy is associated with transient or permanent cognitive dysfunction ranging from subjective complaints to measurable deficits in working memory, attention and language. Given that old age may be related to cognitive decline, the interaction between chemotherapy-induced cognitive impairment and the effects of age is of growing concern in view of our aging population. Chemotherapy-associated cognitive dysfunction may have an additive impact on pre-existing age-related cognitive performance decline, which calls for awareness in its detection, to reduce impact on quality of life and improve management of older patients. We discuss here the « chemobrain », concept, review the existing evidence about pathophysiology, neuroimaging and cognitive phenotype and propose practical tools for routine detection in the outpatient setting., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

New studies confirm the possibility of late thrombolysis. Meta-analyses have confirmed that CGRP inhibitors are efficacious for migraines. Cladribine is a new oral treatment for relapsing-remitting multiple sclerosis. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a new clinical entity accounting for cognitive decline in old patients. The timing of levodopa introduction has no effect on the long-term course of idiopathic Parkinson's disease. Hypophosphatemia helps distinguish between seizures and syncopes in the emergency department. A second course of intravenous immunoglobulins provides no benefit for severe Guillain Barre syndrome. Outdoor therapy improves clinical scales in patients with disorder of consciousness. Ultrasound guided lumbar puncture improves the yield of the procedure., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Purpose: Social cognition disorders after stroke are poorly described. Yet, rehabilitation difficulties are frequent after stroke. This study aimed to evaluate the frequency of social cognition disorders 3 years after a first-ever stroke and to assess the factors associated with this condition. The second aim was to describe all the cognitive domains altered in the same population., Methods: Patients who suffered from a first-ever ischemic or hemorrhagic stroke underwent clinical and neuropsychological assessment, which included the mini-Social cognition and Emotional Assessment (SEA) for evaluating social cognition., Results: The 43 included patients were 67±15 years old, with a median Neurological Institute of Health Stroke Scale (NIHSS) (± interquartile range) at 0±1, and a median modified Rankin Scale (± interquartile range) at 1±1. Twenty patients (46.5%) had poor results in the facial emotions subtest; this factor was associated with a low educational grade (P=0.001). Fourteen patients (34.2%) had poor results on the "faux-pas" recognition subtest; this factor was associated with nonverbal episodic memory disorders (P=0.01). Thirty four patients (79.1%) had cognitive impairment, with at least 1 cognitive domain affected., Conclusions: The study demonstrates the high frequency of social cognition impairment 3 years after the first-ever stroke in young patients. Doctors and nurses should be sensitized to cognitive handicap after stroke because of difficulties for rehabilitation and returning to work.

According to neuropsychological models of anosognosia, there is a failure to transfer on-line awareness of dysfunction into a more generalised long term belief about memory function in Alzheimer's disease. This failure results in specific metamemory deficits for global predictions: patients overestimate their performance before the task but are able to monitor their memory performance after having experienced the task. However, after a delay, they are still not able to make accurate predictions. As previous work has mainly focused on long-term memory, the present study investigates this issue in short-term and working memory. Using both global and item-by-item metacognitive judgements in a digit span task, we showed that Alzheimer's disease patients are as accurate as older adults in monitoring their performance despite impaired memory. When they have the opportunity to test themselves, or when they have already performed the task, patients are able to use feedback to adjust their metacognitive judgements. Overall, these results show that even for a relatively complex task, patients with Alzheimer's disease are aware of their difficulties in the here-and-now., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: We aimed to study the epidemiology of the prodromal and mild stages of Alzheimer's disease (AD) patients who are eligible for clinical trials with disease-modifying therapies., Settings: We analysed two large complementary databases to study the incidence and characteristics of this population on a nationwide scope in France from 2014 to 2018. The National Alzheimer Database contains data from 357 memory centres and 90 private neurologists. Data from 2014 to 2018 have been analysed., Participants: Patients, 50-85 years old, diagnosed with AD who had an Mini-Mental State Exam (MMSE) score of ≥20 were included. We excluded patients with mixed and non-AD neurocognitive disorders., Primary Outcome Measure: Descriptive statistics of the population of interest was the primary measure., Results: In the National Alzheimer Database, 550 198 patients were assessed. Among them, 72 174 (13.1%) were diagnosed with AD and had an MMSE ≥20. Using corrections for specificity of clinical diagnosis of AD, we estimated that about 50 000 (9.1%) had a prodromal or mild AD. In the combined electronic clinical records database of 11 French expert memory centres, a diagnosis of prodromal or mild AD, certified by the use of cerebrospinal fluid AD biomarkers, could be established in 195 (1.3%) out of 14 596 patients., Conclusions: AD was not frequently diagnosed at a prodromal or mild dementia stage in France in 2014 to 2018. Diagnosis rarely relied on a pathophysiological marker even in expert memory centres. National databases will be valuable to monitor early stage AD diagnosis efficacy in memory centres when a disease-modifying treatment becomes available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Thrombolysis and late thrombectomy can be performed in case of compatible radiological imaging. Anti-CGRP monoclonal antibodies seem more effective for the treatment of migraine. Siponimod can reduce significantly disability progression in secondarily progressive MS. Brand-to-generic levetiracetam switching does not cause recrudescence of epileptic seizures. A new definition of Alzheimer's disease using biomarkers of cerebrospinal fluid (CSF) and imaging provides a better understanding of the underlying mechanisms. The use of levodopa-carbidopa intestinal gel and a subcutaneous apomorphine infusion allow a reduction of motor fluctuations in Parkinson's disease. Eculizumab appears as an alternative treatment in severe forms of myasthenia gravis., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

The main aim of this study was to develop a continuous microwave treatment system of whey proteins and then apply this process at 37 °C, 50 °C, 65 °C and 70 °C to achieve pepsinolysis and produce extensively hydrolysed bovine whey protein hydrolysates with low allergenic properties. The microwave process was compared to a conventional thermal treatment with similar temperature set points. Both processes were deeply analysed in terms of the thermal kinetics and operating conditions. The pepsin hydrolysates obtained by the continuous microwave treatment and conventional heating were characterized by SDS-PAGE and RP-HPLC. The allergenicity of the whey protein hydrolysates was explored using a human IgE sensitized rat basophil leukaemia cell assay. The results indicate that extensively hydrolysed whey protein hydrolysates were obtained by microwave only at 65 °C and in a shorter time compared with the conventional thermal treatment. In the same temperature conditions under conventional heating, β-lactoglobulin was resistant to pepsinolysis, and 37% of it remained intact. As demonstrated by an in vitro degranulation assay using specific human IgE-sensitized rat basophils, the extensively hydrolysed whey protein obtained by microwave showed maximum degranulation values of 6.53% compared to those of the native whey protein isolate (45.97%) and hence elicited no more allergenic reactions in basophils. This work emphasizes the potential industrial use of microwave heating specific to milk protein processing to reduce their allergenicity and improve their end-use properties., Competing Interests: Compliance with ethical standardsThe authors declare that there is no conflict of interest.

Background: Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer's disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants., Objective: To describe the proportion of each genetic variation among patients with very young-onset sporadic AD., Methods: We first screened PSEN1, PSEN2, and APP in 154 EOAD patients with an onset before 51 years and a negative family history. Among 99 patients with no mutation (NMC), whole exome sequencing (WES) was performed. We analyzed the APOE genotype and rare protein-truncating or missense predicted damaging variants of TREM2, SORL1, and ABCA7. Neurological examination and cerebrospinal fluid (CSF) biomarkers were systematically retrieved., Results: Nineteen (12.3%) mutation carriers (MC) harbored an APP or PSEN1 pathogenic or likely pathogenic variant. Among the NMC, 54/99 carried at least one genetic risk factor, including 9 APOE4/E4 homozygous, 37 APOE4 heterozygous, and 14 with a rare variant in another risk factor gene: 3 SORL1, 4 TREM2, and 9 ABCA7. MC presented an earlier disease onset (p < 0.0001) and associated neurologic symptoms more frequently (p < 0.002). All but one patient had at least 2 CSF biomarkers in abnormal ranges., Conclusion: The genetic component of very early sporadic EOAD gathers a substantial proportion of pathogenic variants in autosomal dominant genes and an even higher proportion of patients carrying genetic risk factors, suggesting an oligogenic determinism, even at this range of ages.

Introduction: The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory., Methods: We investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose-positron emission tomography evaluations., Results: Encoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions., Discussion: The neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied.

Background: There are now significant evidences that lipid metabolism is affected in numerous neurodegenerative diseases including Alzheimer's disease. These dysfunctions lead to abnormal levels of certain lipids in the brain, cerebrospinal fluid and plasma. It is consequently of interest to establish lipid profiles in neurodegenerative diseases. This approach, which can contribute to identify lipid biomarkers of Alzheimers' disease, can also permit to identify new therapeutic targets. It was therefore of interest to focus on central and peripheral biomarkers in Alzheimer's disease., Methods: A review of the literature on 148 papers was conducted. Based on this literature, the involvement of lipids (cholesterol and oxysterols, fatty acids, phospholipids) in Alzheimer's disease has been proposed., Results: Of the 148 references cited for lipid biomarkers for Alzheimer's disease, 65 refer to cholesterol and oxysterols, 35 to fatty acids and 40 to phospholipids. Among these lipids, some of them such as 24S-hydroxyckolesterol, open up new therapeutic perspectives in gene therapy, in particular. The results on the very long-chain fatty acids suggest the potential of peroxisomal dysfunctions in Alzheimer's disease. As for the phospholipids, they could constitute interesting biomarkers for detecting the disease at the prodromal stage., Conclusion: There are now several lines of evidence that lipids play fundamental roles in the pathogenesis of AD and that some of them have a prognostic and diagnosis value. This may pave the way for the identification of new therapeutic targets, new effective drugs and / or new treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)