Forget About Memory: Disentangling the Amnestic Syndrome in Idiopathic Normal Pressure Hydrocephalus.

Background: Idiopathic normal pressure hydrocephalus (iNPH) can present with both episodic amnestic syndrome and biomarkers of Alzheimer's disease (AD) pathology. Objective: To examine the associations between amnestic syndrome and cerebrospinal fluid (CSF) AD biomarkers in iNPH and the CSF tap test response in iNPH patients with amnestic syndrome. Methods: We used the Free and Cued Selective Reminding Test to divide iNPH into amnestic and non-amnestic patients. We compared their clinical, biological, and radiological characteristics and examined the reversibility of gait spatiotemporal parameters and neuropsychological performances after a CSF tap test. Univariate and multiple linear regression models examined the association between memory performance and clinical-biological characteristics. Results: Sixty-two non-amnestic patients (mean age 77.0±7.0 years, 38.7% female) and thirty-eight amnestic patients (mean age 77.0±5.9 years, 36.8% female) presented similar levels of AD biomarkers and clinical-radiological profiles. Global cognition and education levels were lower in the amnestic iNPH group. We found no association between AD biomarkers and memory performances (total tau: ß= -4.50; 95% CI [-11.96;2.96]; p = 0.236; amyloid-ß (1-42): ß= 8.60, 95% CI [-6.30;23.50]; p = 0.240). At baseline, amnestic iNPH patients performed worse on executive functions, attention, and gait speed but improved similarly to the non-amnestic iNPH patients after the tap test. Conclusions: In our clinical sample of iNPH patients, we confirm the lack of specificity of the amnestic profile for predicting AD pathology. Clinicians should not preclude amnestic iNPH patients from undergoing an invasive procedure of CSF derivation.

The contribution of cognitive reserve in explaining the dual-task walking performance in iNPH patients: comparison with other cognitive, functional, and socio-demographic variables.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a prevalent neurological disorder, but its diagnosis remains challenging. Dual-task (DT) walking performance is a reliable indicator of iNPH but less is known about the role of cognitive reserve (CR) in predicting DT walking performance. AIMS: The objective of this study was to evaluate the contribution of CR on DT walking in healthy controls (HC) and in iNPH patients (iNPH-P). METHODS: 68 iNPH-P (77.2 +/- 6.7 years old) and 28 HC (74.5 +/- 5.7 years old) were evaluated on their single-task walking (Vsimple) and on 4 DT walking (walking and counting or counting backwards, naming animals, naming words beginning with the letter P) (Vcount, VcountB, Vanimals and Vletter respectively). The contribution of CR on the different DT walking speeds was compared between HC and iNPH-P. In iNPH-P, the contribution of CR on the walking speeds was compared with regard to other cognitive, functional, and socio-demographic variables. RESULTS: Simple linear regression demonstrated a moderate influence of CR on single and DT walking speed in iNPH-P (ß > 0.3, p < .001) but not in HC where the relation was not significant. In iNPH-P, results showed that CR played a major role in explaining each of the single and DT walking speeds with NPH-scale. CONCLUSION: As CR could be improved through the life cycle, these results support the idea of developing and supporting physical activity programs that will enrich social, physical, and cognitive resources to protect against age-related functional decline, especially in iNPH-P patients where the age-related deficits are greater.

Amnestic Syndrome in Memory Clinics: Similar Morphological Brain Patterns in Older Adults with and without Alzheimer's Disease.

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.

Normal pressure hydrocephalus and cognitive impairment: The gait phenotype matters too.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is a chronic neurological disease resulting in progressive gait and cognitive disorders. We investigated whether the gait phenotype is associated with the severity of cognitive deficits in iNPH. METHODS: This retrospective study recruited 88 patients (mean age = 76.18 ± 7.21 years, 42% female). Patients were initially referred for suspicion of iNPH and underwent a comprehensive analysis, including gait analysis and cognitive evaluation. RESULTS: In this cohort (27% normal gait, 25% frontal gait, 16% parkinsonian gait, 27% other gait abnormalities), patients with parkinsonian and frontal gait had the lowest Mini-Mental State Examination (MMSE) scores and the slowest gait speed. Patients with normal gait had the highest MMSE scores and gait speed. Frontal gait was associated with lower MMSE score, even after adjusting for age, gender, comorbidities, white matter lesions, and education level (ß = -0.221 [95% confidence interval (CI) = -3.718 to -0.150], p = 0.034). Normal gait was associated with the best MMSE scores, even after adjusting for the abovementioned variables (ß = 0.231 [95% CI = 0.124-3.639], p = 0.036). CONCLUSIONS: Gait phenotypes among iNPH patients are linked to global cognition as assessed with MMSE.

A Decision-Making Algorithm for Remote Digital Assessments of Alzheimer's Disease.

INTRODUCTION: Remote digital assessments (RDAs) such as voice recording, video and motor sensors, olfactory, hearing, and vision screenings are now starting to be employed to complement classical biomarker and clinical evidence to identify patients in the early AD stages. Choosing which RDA can be proposed to individual patients is not trivial and often time-consuming. This position paper presents a decision-making algorithm for using RDA during teleconsultations in memory clinic settings. METHOD: The algorithm was developed by an expert panel following the Delphi methodology. RESULTS: The decision-making algorithm is structured as a series of yes-no questions. The resulting questionnaire is freely available online. DISCUSSION: We suggest that the use of screening questionnaires in the context of memory clinics may help accelerating the adoption of RDA in everyday clinical practice.

Residual Partial Least Squares Learning: Brain Cortical Thickness Simultaneously Predicts Eight Non-pairwise-correlated Behavioural and Disease Outcomes in Alzheimer's Disease.

Alzheimer's Disease (AD) is the leading cause of dementia. It results in cortical thickness changes and is associated with a decline in cognition and behaviour. Such decline affects multiple important day-to-day functions, including memory, language, orientation, judgment and problem-solving. Recent research has made important progress in identifying brain regions associated with single outcomes, such as individual AD status and general cognitive decline. The complex projection from multiple brain areas to multiple AD outcomes, however, remains poorly understood. This makes the assessment and especially the prediction of multiple AD outcomes - each of which may unveil an integral yet different aspect of the disease - challenging, particularly when some are not strongly correlated. Here, uniting residual learning, partial least squares (PLS), and predictive modelling, we develop an explainable, generalisable, and reproducible method called the Residual Partial Least Squares Learning (the re-PLS Learning) to (1) chart the pathways between large-scale multivariate brain cortical thickness data (inputs) and multivariate disease and behaviour data (outcomes); (2) simultaneously predict multiple, non-pairwise-correlated outcomes; (3) control for confounding variables (e.g., age and gender) affecting both inputs and outcomes and the pathways in-between; (4) perform longitudinal AD disease status classification and disease severity prediction. We evaluate the performance of the proposed method against a variety of alternatives on data from AD patients, subjects with mild cognitive impairment (MCI), and cognitively normal individuals (n=1,196) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our results unveil pockets of brain areas in the temporal, frontal, sensorimotor, and cingulate areas whose cortical thickness may be respectively associated with declines in different cognitive and behavioural subdomains in AD. Finally, we characterise re-PLS' geometric interpretation and mathematical support for delivering meaningful neurobiological insights and provide an open software package (re-PLS) available at https://github.com/thanhvd18/rePLS.

Circulating Biomarkers for Alzheimer's Disease: Unlocking the Diagnostic Potential in Low- and Middle-Income Countries, Focusing on Africa.

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.

Persistence and emergence of new neuropsychological deficits following SARS-CoV-2 infection: A follow-up assessment of the Geneva COVID-COG cohort.

Background: Despite numerous observations of neuropsychological deficits immediately following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, little is known about what happens to these deficits over time and whether they are affected by changes in fatigue and any psychiatric symptoms. We aimed to assess the prevalence of neuropsychological deficits at 6-9 months and again at 12-15 months after coronavirus disease 2019 (COVID-19) and to explore whether it was associated with changes in fatigue and psychiatric symptoms. Methods: We administered a series of neuropsychological tests and psychiatric questionnaires to 95 patients (mean age = 57.12 years, standard deviation (SD) = 10.68; 35.79% women) 222 (time point 1 (T1)) and 441 (time point 2 (T2)) days on average after infection. Patients were categorised according to the severity of their respiratory COVID-19 symptoms in the acute phase: mild (no hospitalisation), moderate (conventional hospitalisation), and severe (hospitalisation in intensive care unit (ICU) plus mechanical ventilation). We ran Monte-Carlo simulation methods at each time point to generate a simulated population and then compared the cumulative percentages of cognitive disorders displayed by the three patient subgroups with the estimated normative data. We calculated generalised estimating equations for the whole sample to assess the longitudinal associations between cumulative neuropsychological deficits, fatigue, and psychiatric data (anxiety, depressive symptoms, posttraumatic stress disorder, and apathy). Results: Most participants (>50%) exhibited a decrease in their neuropsychological impairments, while approximately 25% showed an escalation in these cognitive deficits. At T2, patients in the mild subgroup remained free of accumulated neuropsychological impairments. Patients with moderate severity of symptoms displayed a decrease in the magnitude of cumulative deficits in perceptual and attentional functions, a persistence of executive, memory and logical reasoning deficits, and the emergence of language deficits. In patients with severe symptoms, perceptual deficits emerged and executive deficits increased, while attentional and memory deficits remained unchanged. Changes in executive functions were significantly associated with changes in depressive symptoms, but the generalised estimating equations failed to reveal any other significant effect. Conclusion: While most cumulative neuropsychological deficits observed at T1 persisted and even worsened over time in the subgroups of patients with moderate and severe symptoms, a significant proportion of patients, mainly in the mild subgroup, exhibited improved performances. However, we identified heterogeneous neuropsychological profiles both cross-sectionally and over time, suggesting that there may be distinct patient phenotypes. Predictors of these detrimental dynamics have yet to be identified.

High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study.

OBJECTIVES: Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group. METHOD: Thirty-six patients with COVID-19 AE (mean age 72.6 ± 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 ± 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 ± 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored. RESULTS: The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014). CONCLUSION: This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19.

[Neurology: what's new in 2023]. / Neurologie: ce qui a changé en 2023.

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.

L'année 2023 est marquée par l'arrivée sur le marché du lécanémab pour le traitement de la maladie d'Alzheimer. De nouveaux biomarqueurs ont démontré leur utilité dans le suivi des neuropathies périphériques ou dans le diagnostic des synucléinopathies. Une étude génétique a mis en évidence le rôle des cellules du système nerveux dans le risque de progression de la sclérose en plaques (SEP). Les effets indésirables des traitements anticonvulsivants lors d'exposition prénatale ou sur le métabolisme des lipides ont été précisés. De nouveaux traitements anti-CGRP ont démontré leur efficacité dans les crises migraineuses et les migraines chroniques. Les critères de thrombectomie se sont encore élargis. Et enfin, la réhabilitation affine la prise en charge des patients cérébrovasculaires et de ceux atteints d'une SEP secondaire progressive.

Evidence for increased parallel information transmission in human brain networks compared to macaques and male mice.

Brain communication, defined as information transmission through white-matter connections, is at the foundation of the brain's computational capacities that subtend almost all aspects of behavior: from sensory perception shared across mammalian species, to complex cognitive functions in humans. How did communication strategies in macroscale brain networks adapt across evolution to accomplish increasingly complex functions? By applying a graph- and information-theory approach to assess information-related pathways in male mouse, macaque and human brains, we show a brain communication gap between selective information transmission in non-human mammals, where brain regions share information through single polysynaptic pathways, and parallel information transmission in humans, where regions share information through multiple parallel pathways. In humans, parallel transmission acts as a major connector between unimodal and transmodal systems. The layout of information-related pathways is unique to individuals across different mammalian species, pointing at the individual-level specificity of information routing architecture. Our work provides evidence that different communication patterns are tied to the evolution of mammalian brain networks.

[Practical management of post-COVID-19 condition. Update and illustration by clinical situations]. / Prise en charge pratique de l'affection post-Covid-19. Mise à jour et illustration par des situations cliniques.

Persistent manifestations of COVID-19, known as «long COVID¼ or post-COVID-19 condition (RA02, CIM-11), affect many infected individuals, with a 24-month prevalence depending on the studies context (18 % in a recent Swiss study). The diversity of clinical presentation, the sometimes complex diagnostic methods, and the multidisciplinary management highlight the importance of a holistic approach, with practical advice for assessing work capacity in the outpatient setting. This article offers an update and synthesis of current knowledge concerning post-COVID-19 condition with practical recommendations for primary care medicine, illustrated by real clinical situations.

Les manifestations persistantes du Covid-19, connues sous le nom de « Covid long ¼ ou affection post-Covid-19 (RA02, CIM-11), concernent un nombre significatif de personnes infectées, avec une prévalence à 24 mois de l'infection variant en fonction des études et du contexte (18 % dans une étude suisse récente). La diversité de présentation clinique, les méthodes diagnostiques, parfois complexes, et les approches multidisciplinaires pour la prise en charge soulignent l'importance d'une approche holistique. Cet article propose une mise à jour et une synthèse des connaissances actuelles concernant l'affection post-Covid-19, avec des recommandations pratiques de prise en charge en médecine de premiers recours, illustrées par des situations cliniques réelles et des conseils pratiques pour l'appréciation de la capacité de travail.

ER2 risk levels and their association with incident falls, their recurrence and post-fall fractures in older women: Results of the EPIDOS study.

BACKGROUND: "Emergency Room Evaluation and Recommendations" (ER2) is a validated clinical tool which stratifies the risk of the occurrence of adverse outcomes in three levels (i.e., low, moderate and high) in older people attending emergency departments. This study examines the association of ER2 risk levels with incident falls, their recurrence and post-fall fractures in older community women. METHODS: 7147 participants of the EPIDémiologie de l'OStéoporose (EPIDOS) study - an observational population-based cohort study - were selected. ER2 low, moderate and high risk levels were determined at baseline. Incident fall outcomes (i.e., one incident fall without fracture, one incident fall with fracture, ≥2 falls without fracture and ≥ 2 falls with fracture) were collected prospectively every 4 months over a 4-year follow-up period. RESULTS: The overall incidence of falls was 26.4.%, regardless of their characteristics. ER2 low risk level (hazard ratio (HR) ≤0.80 with P ≤ 0.001) and high risk (HR ≥ 1.26 with P ≤ 0.001) were associated respectively with low and high incident fall outcomes, except for recurrent falls without fracture. CONCLUSIONS: ER2 low and high risk levels were associated with incident falls outcomes in EPIDOS participants, suggesting that the ER2 tool may be useful for stratifying the risk of falls in the older population.

Obstructive sleep apnea: a major risk factor for COVID-19 encephalopathy?

BACKGROUND: This study evaluates the impact of high risk of obstructive sleep apnea (OSA) on coronavirus disease 2019 (COVID-19) acute encephalopathy (AE). METHODS: Between 3/1/2020 and 11/1/2021, 97 consecutive patients were evaluated at the Geneva University Hospitals with a neurological diagnosis of COVID-19 AE. They were divided in two groups depending on the presence or absence of high risk for OSA based on the modified NOSAS score (mNOSAS, respectively ≥ 8 and < 8). We compared patients' characteristics (clinical, biological, brain MRI, EEG, pulmonary CT). The severity of COVID-19 AE relied on the RASS and CAM scores. RESULTS: Most COVID-19 AE patients presented with a high mNOSAS, suggesting high risk of OSA (> 80%). Patients with a high mNOSAS had a more severe form of COVID-19 AE (84.8% versus 27.8%), longer mean duration of COVID-19 AE (27.9 versus 16.9 days), higher mRS at discharge (≥ 3 in 58.2% versus 16.7%), and increased prevalence of brain vessels enhancement (98.1% versus 20.0%). High risk of OSA was associated with a 14 fold increased risk of developing a severe COVID-19 AE (OR = 14.52). DISCUSSION: These observations suggest an association between high risk of OSA and COVID-19 AE severity. High risk of OSA could be a predisposing factor leading to severe COVID-19 AE and consecutive long-term sequalae.

Markers of limbic system damage following SARS-CoV-2 infection.

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P < 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.