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.

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.

The Taxonomy of Subjective Cognitive Decline: Proposal and First Clinical Evidence from the Geneva Memory Clinic Cohort.

INTRODUCTION: Subjective cognitive decline (SCD) is characterized by subjective cognitive concerns without objective cognitive impairment and is considered a risk factor for cognitive decline and dementia. However, most SCD patients will not develop neurodegenerative disorders, yet they may suffer from minor psychiatric, neurological, or somatic comorbidities. The aim of the present study was to provide a taxonomy of the heterogeneous SCD entity and to conduct a preliminary validation using data from a memory clinic sample. METHODS: Participants were fifty-five SCD individuals consecutively recruited at the Geneva Memory Center. Based on clinical reports, they were classified into three clinically pre-defined subgroups: (i) those with psychological or psychiatric comorbidities (Psy), (ii) those with somatic comorbidities (SomCom), (iii) and those with no apparent cause (NAC). Baseline demographics, clinical, cognitive, and biomarker differences among the SCD subgroups were assessed. Longitudinal cognitive changes (average 3 years follow-up) were modeled using a linear mixed model. RESULTS: Out of the 55 SCD cases, 16 were SomCom, 18 Psy, and 21 NAC. 47% were female, mean age was 71 years. We observed higher frequency of APOE ε4 carriers in NAC (53%) compared to SomCom (14%) and Psy (0%, p = 0.023) and lower level of plasma Aß42 in NAC (6.8 ± 1.0) compared to SomCom (8.4 ± 1.1; p = 0.031). SomCom subjects were older (74 years) than Psy (67 years, p = 0.011), and had greater medial temporal lobe atrophy (1.0 ± 1.0) than Psy (0.2 ± 0.6) and NAC (0.4 ± 0.5, p = 0.005). SomCom has worse episodic memory performances (14.5 ± 3.5) than Psy (15.8 ± 0.4) and NAC (15.8 ± 0.7, p = 0.032). We observed a slightly steeper, yet not statistically significant, cognitive decline in NAC (ß = -0.48) compared to Psy (ß = -0.28) and SomCom (ß = -0.24). CONCLUSIONS: NAC features a higher proportion of APOE ε4 carriers, lower plasma Aß42 and a trend towards steeper cognitive decline than SomCom and Psy. Taken together, these findings suggest that NACs are at higher risk of cognitive decline due to AD. The proposed clinical taxonomy might be implemented in clinical practice to identify SCD at higher risk. However, such taxonomy should be tested on an independent cohort with a larger sample size.

[Early cognitive rehabilitation for patients with severe neurological impairment]. / Prise en charge cognitive précoce des patients cérébrolésés sévères.

Improving the state and future of patients severely impaired following brain injury is at the heart of early rehabilitation, established from the first days of hospitalization. For cognitive deficits, this management involves several challenges, related to hospital conditions and to the patients' capacities during the acute phase. A relevant intervention can be provided, as long as it involves an assessment adapted to these particularities and a rehabilitation targeting the most limiting deficits at this stage. These findings, discussed in the light of our clinical experience and current knowledge in the field, have yet to be scientifically tested since randomized clinical trials are still lacking. The integration of new technologies to facilitate the bedside work presents another prospect for the future.

Améliorer sans délai l'état et le devenir des patients sévèrement touchés par une lésion cérébrale constitue l'essence de la rééducation précoce, instaurée dès les premiers jours de l'hospitalisation. Pour les aspects cognitifs, cette prise en charge comporte plusieurs défis, liés aux conditions hospitalières et aux capacités des patients. Une intervention pertinente peut être pratiquée, sous réserve d'une évaluation adaptée à ces particularités et d'une rééducation ciblant les déficits les plus limitants à ce stade. Ces constats, discutés à la lumière de notre expérience clinique et des connaissances actuelles, doivent encore être prouvés scientifiquement car les essais cliniques randomisés manquent cruellement. L'intégration des nouvelles technologies pour faciliter le travail au chevet des patients constitue une autre perspective d'avenir.

Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

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.

Neglecting the bottom space: an object-based disorder? A two-case observational study.

Altitudinal neglect is an atypical form of spatial neglect where brain-damaged patients neglect the lower, or sometimes the upper, part of the space. Our understanding of this phenomena is limited, with unknown occurrence across different reference frames, such as distance (peripersonal vs. extrapersonal) and system of reference (egocentric vs. allocentric). Two patients with acute bilateral (P1) or right hemispheric (P2) stroke, with signs of bottom altitudinal neglect, underwent an extensive evaluation of neglect within 10 days post-stroke. Assessments involved altitudinal neglect and unilateral spatial neglect (USN) in peripersonal space, exploring egocentric and allocentric signs and in extrapersonal space. Compared to a control group of 15 healthy age-matched subjects, patients showed allocentric and egocentric left USN in peripersonal space, and mostly allocentric signs of altitudinal neglect. No signs of neglect were evidenced in extrapersonal space. Altitudinal neglect could thus present as an allocentric form of spatial neglect, suggesting that allocentric representations may not only affect the deployment of attentional resources along horizontal dimensions but also operate along vertical dimensions. Future studies should deepen our understanding of altitudinal neglect, eventually leading to further unravel spatial processes that control attention, their corresponding brain mechanisms, and implications for patients' rehabilitation and functional outcome.

[Cerebral amyloid angiopathy-related cognitive decline: small vessels, big problems]. / Déclin cognitif vasculaire et angiopathie amyloïde cérébrale : petits vaisseaux, gros problèmes.

Cerebral amyloid angiopathy (CAA) is a common and well-defined small vessel disease characterized by the deposition of amyloid ß in the vascular wall. CAA causes devastating outcomes related to intracerebral hemorrhage and cognitive decline in older adults. The shared pathogenic pathway between CAA and Alzheimer's disease, co-occuring frequently in the same subject, has important implications for cognitive outcomes and novel anti-amyloid-ß immunotherapies. In this review, we present the epidemiology, pathophysiology, current diagnostic criteria of CAA, and future developments in the field.

L'angiopathie amyloïde cérébrale (AAC) est une maladie fréquente des petits vaisseaux, caractérisée par un dépôt de ß-amyloïde dans la paroi vasculaire entraînant des hémorragies cérébrales et un déclin cognitif. L'AAC et la maladie d'Alzheimer présentent des caractéristiques physiopathologiques communes et peuvent se retrouver chez un même individu. Cela influence le tableau cognitif et sera à prendre en compte lors de l'utilisation prochaine des nouvelles immunothérapies anti-amyloïde. Dans cet article, nous passons en revue l'épidémiologie, la pathophysiologie, les présentations cliniques ainsi que les critères diagnostiques de l'AAC et discutons des futurs développements dans le domaine.

[Dementia with Lewy bodies: state of the art and perspectives for the clinician]. / Démence à corps de Lewy : état de l'art et perspectives pour le clinicien.

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia, after Alzheimer's disease (AD) and vascular dementia. Its diagnosis remains a challenge for the clinician because of the variety of clinical presentations and comorbidities. The diagnosis is based on clinical criteria such as cognitive fluctuations, visual hallucinations, progressive cognitive impairment, Parkinsonian signs and REM sleep behavioral disorder. Although not specific, biomarkers are helpful for increasing the likelihood of LBD diagnosis and for differentiating LBD from other differential diagnoses such as Parkinson's disease with dementia and Alzheimer's disease. Clinicians should be aware of LBD clinical features and actively look for them in patients with cognitive symptoms, take into consideration the often-associated co-pathologies and to optimize patient's management.

La démence à corps de Lewy (DCL) est l'une des démences les plus fréquentes, après la maladie d'Alzheimer (MA) et la démence vasculaire. Son diagnostic est un défi pour le clinicien du fait de la variété des présentations cliniques et des comorbidités. Le diagnostic repose sur des critères cliniques comme des fluctuations cognitives, des hallucinations visuelles, des troubles cognitifs progressifs, des signes parkinsoniens et un trouble comportemental du sommeil paradoxal. L'utilisation des biomarqueurs, bien que non spécifiques, permet d'augmenter la probabilité de diagnostic de la DCL et de la différencier de la maladie de Parkinson avec démence et de la MA. De ce fait, devant tout sujet âgé avec trouble cognitif, une recherche des symptômes de la DCL est à réaliser en considérant aussi les traitements iatrogènes et les copathologies.

[Post-COVID-19 neuropsychological syndrome]. / Syndrome post-Covid-19 neuropsychologique.

Recent observations suggest the persistence of neurological and neuropsychological symptoms in the long-term following SARS-CoV-2 infection. Currently described within the post-COVID-19 syndrome. The objective of this article is to discuss recent epidemiological data and data from neuroimaging studies. Finally, a discussion is proposed regarding recent suggestions regarding the existence of distinct phenotypes of post-COVID-19 syndrome.

De récentes observations suggèrent la persistance de symptômes neurologiques et neuropsychologiques à long terme suite à une infection par le SARS-CoV-2, actuellement décrit au sein du syndrome post-Covid-19. L'objectif de cet article est d'aborder les récentes données épidémiologiques et les données provenant d'études en neuro-imagerie. Finalement, une discussion est proposée quant aux récentes suggestions concernant l'existence de phénotypes distincts au sein du syndrome post-Covid-19.

[Long COVID : neurological aspects]. / Covid long : aspects neurologiques.

The study of post-COVID-19 symptomatology revealed a first wave of post-acute (persistence of symptoms less than 3 months) neurocognitive symptoms. However, some of these symptoms worsened, while others improved. To our knowledge, these symptoms may persist for up to 1 to 2 years after infection. The intensity, variability and persistence of neurocognitive symptoms may rise the hypotheses of accelerated neurodegenerative processes, as well as neuropsychiatric and/or genetic vulnerabilities that are still poorly understood. Moreover, the multi-organ manifestations of post-COVID-19 symptoms remind us of the importance of promoting an interdisciplinary perspective at both clinical and fundamental levels. Finally, many social and economic issues parallel to the neuropathological consequences remain to be investigated.

L'étude de la symptomatologie post-Covid-19 a permis de mettre en évidence une première vague de symptômes neurocognitifs postaigus (persistance des symptômes inférieurs à 3 mois). Certains se sont aggravés, tandis que d'autres se sont améliorés. Ils peuvent perdurer jusqu'à 1 à 2 ans après l'infection. L'intensité, la variabilité et la persistance des symptômes neurocognitifs pourraient suggérer des hypothèses d'accélération de processus neurodégénératifs et des vulnérabilités neuropsychiatriques et/ou génétiques encore mal comprises. De plus, les manifestations multi-organiques des symptômes post-Covid-19 nous rappellent l'importance de promouvoir une perspective multidisciplinaire sur les plans clinique et fondamental. Finalement, de nombreuses questions sociales et économiques parallèles aux conséquences neuropathologiques restent à investiguer.

Lifelong bilingualism and mechanisms of neuroprotection in Alzheimer dementia.

Lifelong bilingualism is associated with delayed dementia onset, suggesting a protective effect on the brain. Here, we aim to study the effects of lifelong bilingualism as a dichotomous and continuous phenomenon, on brain metabolism and connectivity in individuals with Alzheimer's dementia. Ninety-eight patients with Alzheimer's dementia (56 monolinguals; 42 bilinguals) from three centers entered the study. All underwent an [18F]-fluorodeoxyglucose positron emission tomography (PET) imaging session. A language background questionnaire measured the level of language use for conversation and reading. Severity of brain hypometabolism and strength of connectivity of the major neurocognitive networks was compared across monolingual and bilingual individuals, and tested against the frequency of second language life-long usage. Age, years of education, and MMSE score were included in all above mentioned analyses as nuisance covariates. Cerebral hypometabolism was more severe in bilingual compared to monolingual patients; severity of hypometabolism positively correlated with the degree of second language use. The metabolic connectivity analyses showed increased connectivity in the executive, language, and anterior default mode networks in bilingual compared to monolingual patients. The change in neuronal connectivity was stronger in subjects with higher second language use. All effects were most pronounced in the left cerebral hemisphere. The neuroprotective effects of lifelong bilingualism act both against neurodegenerative processes and through the modulation of brain networks connectivity. These findings highlight the relevance of lifelong bilingualism in brain reserve and compensation, supporting bilingual education and social interventions aimed at usage, and maintenance of two or more languages, including dialects, especially crucial in the elderly people.

Crossed functional specialization between the basal ganglia and cerebellum during vocal emotion decoding: Insights from stroke and Parkinson's disease.

There is growing evidence that both the basal ganglia and the cerebellum play functional roles in emotion processing, either directly or indirectly, through their connections with cortical and subcortical structures. However, the lateralization of this complex processing in emotion recognition remains unclear. To address this issue, we investigated emotional prosody recognition in individuals with Parkinson's disease (model of basal ganglia dysfunction) or cerebellar stroke patients, as well as in matched healthy controls (n = 24 in each group). We analysed performances according to the lateralization of the predominant brain degeneration/lesion. Results showed that a right (basal ganglia and cerebellar) hemispheric dysfunction was likely to induce greater deficits than a left one. Moreover, deficits following left hemispheric dysfunction were only observed in cerebellar stroke patients, and these deficits resembled those observed after degeneration of the right basal ganglia. Additional analyses taking disease duration / time since stroke into consideration revealed a worsening of performances in patients with predominantly right-sided lesions over time. These results point to the differential, but complementary, involvement of the cerebellum and basal ganglia in emotional prosody decoding, with a probable hemispheric specialization according to the level of cognitive integration.

One-year persistent symptoms and functional impairment in SARS-CoV-2 positive and negative individuals.

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

The Two-Way Route between Delirium Disorder and Dementia: Insights from COVID-19.

BACKGROUND: Delirium disorder is a frequent neurological complication of SARS-CoV-2 infection and associated with increased disease severity and mortality. Cognitive impairment is a major risk factor for developing delirium disorder during COVID-19, which, in turn, increases the risk of subsequent neurological complications and cognitive decline. SUMMARY: The bidirectional connection between delirium disorder and dementia likely resides at multiple levels, and its pathophysiological mechanisms during COVID-19 include endothelial damage, blood-brain barrier dysfunction, and local inflammation, with activation of microglia and astrocytes. Here, we describe the putative pathogenic pathways underlying delirium disorder during COVID-19 and highlight how they cross with the ones leading to neurodegenerative dementia. KEY MESSAGES: The analysis of the two-sided link can offer useful insights for confronting with long-term neurological consequences of COVID-19 and framing future prevention and early treatment strategies.

Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test.

Idiopathic Normal Pressure Hydrocephalus (iNPH)-the leading cause of reversible dementia in aging-is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH-specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer's disease (AD). Here we investigate the resting-state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer's pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive-control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD-pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross-network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.

COVID-19 encephalopathy: Clinical and neurobiological features.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has been associated with neurological complications, including acute encephalopathy. To better understand the neuropathogenesis of this acute encephalopathy, we describe a series of patients with coronavirus disease 2019 (COVID-19) encephalopathy, highlighting its phenomenology and its neurobiological features. On May 10, 2020, 707 patients infected by SARS-CoV-2 were hospitalized at the Geneva University Hospitals; 31 (4.4%) consecutive patients with an acute encephalopathy (64.6 ± 12.1 years; 6.5% female) were included in this series, after exclusion of comorbid neurological conditions, such as stroke or meningitis. The severity of the COVID-19 encephalopathy was divided into severe and mild based on the Richmond Agitation Sedation Scale (RASS): severe cases (n = 14, 45.2%) were defined on a RASS < -3 at worst presentation. The severe form of this so-called COVID-19 encephalopathy presented more often a headache. The severity of the pneumonia was not associated with the severity of the COVID-19 encephalopathy: 28 of 31 (90%) patients did develop an acute respiratory distress syndrome, without any difference between groups (p = .665). Magnetic resonance imaging abnormalities were found in 92.0% (23 of 25 patients) with an intracranial vessel gadolinium enhancement in 85.0% (17 of 20 patients), while an increased cerebrospinal fluid/serum quotient of albumin suggestive of blood-brain barrier disruption was reported in 85.7% (6 of 7 patients). Reverse transcription-polymerase chain reaction for SARS-CoV-2 was negative for all patients in the cerebrospinal fluid. Although different pathophysiological mechanisms may contribute to this acute encephalopathy, our findings suggest the hypothesis of disturbed brain homeostasis and vascular dysfunction consistent with a SARS-CoV-2-induced endotheliitis.

Diagnostic value of amyloid-PET and tau-PET: a head-to-head comparison.

PURPOSE: Assess the individual and combined diagnostic value of amyloid-PET and tau-PET in a memory clinic population. METHODS: Clinical reports of 136 patients were randomly assigned to two diagnostic pathways: AMY-TAU, amyloid-PET is presented before tau-PET; and TAU-AMY, tau-PET is presented before amyloid-PET. Two neurologists independently assessed all reports with a balanced randomized design, and expressed etiological diagnosis and diagnostic confidence (50-100%) three times: (i) at baseline based on the routine diagnostic workup, (ii) after the first exam (amyloid-PET for the AMY-TAU pathway, and tau-PET for the TAU-AMY pathway), and (iii) after the remaining exam. The main outcomes were changes in diagnosis (from AD to non-AD or vice versa) and in diagnostic confidence. RESULTS: Amyloid-PET and tau-PET, when presented as the first exam, resulted in a change of etiological diagnosis in 28% (p = 0.006) and 28% (p < 0.001) of cases, and diagnostic confidence increased by 18% (p < 0.001) and 19% (p < 0.001) respectively, with no differences between exams (p > 0.05). We observed a stronger impact of a negative amyloid-PET versus a negative tau-PET (p = 0.014). When added as the second exam, amyloid-PET and tau-PET resulted in a further change in etiological diagnosis in 6% (p = 0.077) and 9% (p = 0.149) of cases, and diagnostic confidence increased by 4% (p < 0.001) and 5% (p < 0.001) respectively, with no differences between exams (p > 0.05). CONCLUSION: Amyloid-PET and tau-PET significantly impacted diagnosis and diagnostic confidence in a similar way, although a negative amyloid-PET has a stronger impact on diagnosis than a negative tau-PET. Adding either of the two as second exam further improved diagnostic confidence. TRIAL NUMBER: PB 2016-01346.

Normal pressure hydrocephalus and CSF tap test response: the gait phenotype matters.

This study compared gait speed changes after CSF tap test in patients with idiopathic normal pressure hydrocephalus presenting with various gait phenotypes (frontal, parkinsonian, normal, or other). All patients improved, except those with parkinsonian gait.

C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy.

Encephalopathy is a neurological complication of COVID-19. The objective of this exploratory study is to investigate the link between systemic inflammation and brain microstructural changes (measured by diffusion-weighted imaging) in patients with COVID-19 encephalopathy. 20 patients with COVID-19 encephalopathy (age: 67.3 [Formula: see text] 10.0 years; 90% men) hospitalized in the Geneva University Hospitals for a SARS-CoV-2 infection between March and May 2020 were included in this retrospective cohort study. COVID-19 encephalopathy was diagnosed following a comprehensive neurobiological evaluation, excluding common causes of delirium, such as hypoxemic or metabolic encephalopathy. We investigated the correlation between systemic inflammation (measured by systemic C-reactive protein (CRP)) and brain microstructural changes in radiologically normal white matter (measured by apparent diffusion coefficient (ADC)) in nine spatially widespread regions of the white matter previously associated with delirium. Systemic inflammation (CRP = 60.8 ± 50.0 mg/L) was positively correlated with ADC values in the anterior corona radiata (p = 0.0089), genu of the corpus callosum (p = 0.0064) and external capsule (p = 0.0086) after adjusting for patients' age. No statistically significant association between CRP and ADC was found in the other six white matter regions. Our findings indicate high risk of white matter abnormalities in COVID-19 encephalopathy patients with high peripheral inflammatory markers, suggesting aggressive imaging monitoring may be warranted in these patients. Future studies should clarify a possible specificity of the spatial patterns of CRP-white matter microstructure association in COVID-19 encephalopathy patients and disentangle the role of individual cytokines on brain inflammatory mechanisms.