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Idiopathic normal pressure hydrocephalus (iNPH), a leading cause of reversible dementia in older adults, is marked by ventriculomegaly, gait disturbances, cognitive decline, and urinary incontinence. Emerging evidence suggests that gut dysbiosis (microbial imbalance) may influence neuroinflammation and cerebrospinal fluid dynamics, potentially contributing to glymphatic system dysfunction and ventricular enlargement. This study used shotgun metagenomics to analyze the gut microbiome in iNPH patients (n = 18) compared to healthy controls (n = 50), individuals with ventriculomegaly but no iNPH symptoms (n = 50), and Alzheimer’s disease patients (n = 50). Microbiome analysis showed an enrichment of species previously linked to various disease states, such as Enterocloster bolteae and Ruminococcus gnavus , indicating general dysbiosis. In contrast, enrichment of specific taxa, including Evtepia gabavorous and Cuneatibacter sp. , were specifically associated with iNPH clinical traits, pointing to possible disease-specific microbial markers. Functional analysis showed enrichment of pathways related to carbohydrate and amino acid metabolism, including the S-adenosyl-L-methionine superpathway, implicating inflammatory and immune processes. These findings suggest distinct gut microbiome signatures in iNPH, offering insights into potential gut-brain interactions that may contribute to the disorder’s pathophysiology and highlighting possible targets for future therapeutic strategies.

Feeling of presence (FOP) refers to the vivid sensation of a person’s presence near oneself and is common in Dementia with Lewy Bodies (DLB). Based on previous observations on epileptic subjects, we hypothesized that DLB subjects with FOP would harbour 18F-fluorodeoxyglucose PET hypometabolism in left parietal areas. 25 subjects (mean age 71.9 ± 6.7, disease duration at scan 1.7 ± 1.5 years) were included in the study, of whom nine (36%) experienced FOP. No significant between-group difference was observed regarding dopamine transporters striatal uptake (p = 0.64), daily dopaminergic treatment dosage (p = 0.88) and visual hallucinations (p = 0.83). Statistical parametric mapping showed that subjects with FOP had a significantly reduced glucose metabolism in several left frontoparietal areas (p < 0.001), including superior parietal lobule and precuneus. Interregional correlation analysis of these areas showed specific connectivity with right insula and putamen in the FOP subgroup and right orbitofrontal and superior frontal in subjects without FOP. This provides further evidence about the role of a left frontoparietal network and suggest a possible contribution of impaired orbitofrontal reality filtering associated with FOP.

PurposeTo compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm.MethodsTwo independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker.ResultsAmong patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3.ConclusionsAmyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence.Trial registrationEudraCT no.: 2014-005389-31

Purpose: The clinical diagnosis of motor speech disorders (MSDs) is mainly based on perceptual approaches. However, studies on perceptual classification of MSDs often indicate low classification accuracy. The aim of this study was to determine in a forced-choice dichotomous decision-making task (a) how accuracy of speech-language pathologists (SLPs) in perceptually classifying apraxia of speech (AoS) and dysarthria is impacted by speech task, severity of MSD, and listener's expertise and (b) which perceptual features they use to classify. Method: Speech samples from 29 neurotypical speakers, 14 with hypokinetic dysarthria associated with Parkinson's disease (HD), 10 with poststroke AoS, and six with mixed dysarthria associated with amyotrophic lateral sclerosis (MD-FlSp [combining flaccid and spastic dysarthria]), were classified by 20 expert SLPs and 20 student SLPs. Speech samples were elicited in spontaneous speech, text reading, oral diadochokinetic (DDK) tasks, and a sample concatenating text reading and DDK. For each recorded speech sample, SLPs answered three dichotomic questions following a diagnostic approach, (a) neurotypical versus pathological speaker, (b) AoS versus dysarthria, and (c) MD-FlSp versus HD, and a multiple-choice question on the features their decision was based on. Results: Overall classification accuracy was 72% with good interrater reliability, varying with SLP expertise, speech task, and MSD severity. Correct classification of speech samples was higher for speakers with dysarthria than for AoS and higher for HD than for MD-FlSp. Samples elicited with continuous speech reached the best classification rates. An average number of three perceptual features were used for correct classifications, and their type and combination differed between the three MSDs. Conclusions: The auditory-perceptual classification of MSDs in a diagnostic approach reaches substantial performance only in expert SLPs with continuous speech samples, albeit with lower accuracy for AoS. Specific training associated with objective classification tools seems necessary to improve recognition of neurotypical speech and distinction between AoS and dysarthria.

Background and Purpose Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with several complications of the central nervous system (CNS), including acute encephalopathy. Methods In this pilot study, we report a series of 39 patients (66.5 ± 9.2 years; 10.3% female) with acute encephalopathy, who underwent a standard brain magnetic resonance imaging (MRI) at 1.5 T during the acute symptomatic phase. In addition to diffusion-weighted imaging, MR angiography and susceptibility-weighted images, high-resolution vascular black blood sequences (in 34 cases) were used to investigate the vasculature of the brain. Results In 29 out of 34 patients with COVID-19 encephalopathy (85%) with high-resolution vessel wall imaging, we found a circular enhancement and thickening of the basilar and vertebral arteries, without any correlation with ischemia or microbleeds (reported in 21% and 59%, respectively). Conclusion We report a high prevalence of vascular changes suggestive of endotheliitis as reported in other organs. This could suggest an inflammatory mechanism underlying this 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.

Background and objective Phosphorylated tau ( p -tau) 217 has recently received attention because it seems more reliable than other p -tau variants for identifying Alzheimer’s disease (AD) pathology. Thus, we aimed to compare the diagnostic accuracy of plasma and CSF p -tau217 with p -tau181 and p -tau231 in a memory clinic cohort. Methods The study included 114 participants (CU = 33; MCI = 67; Dementia = 14). The p -tau variants were correlated versus continuous measures of amyloid (A) and tau (T)-PET. The p -tau phospho-epitopes were assessed through: (i) effect sizes ( δ ) between diagnostic and A ± and T ± groups; (ii) receiver operating characteristic (ROC) analyses in A-PET and T-PET. Results The correlations between both plasma and CSF p -tau217 with A-PET and T-PET ( r range 0.64–0.83) were stronger than those of p -tau181 ( r range 0.44–0.79) and p -tau231 ( r range 0.46–0.76). Plasma p -tau217 showed significantly higher diagnostic accuracy than p -tau181 and p -tau231 in (i) differences between diagnostic and biomarker groups ( δ range : p -tau217 = 0.55–0.96; p -tau181 = 0.51–0.67; p -tau231 = 0.53–0.71); (ii) ROC curves to identify A-PET and T-PET positivity (AUC average : p -tau217 = 0.96; p -tau181 = 0.76; p -tau231 = 0.79). On the other hand, CSF p -tau217 (AUC average  = 0.95) did not reveal significant differences in A-PET and T-PET AUC than p -tau181 (AUC average  = 0.88) and p -tau231 (AUC average  = 0.89). Discussion Plasma p -tau217 demonstrated better performance in the identification of AD pathology and clinical phenotypes in comparison with other variants of p -tau in a memory clinic cohort. Furthermore, p -tau217 had comparable performance in plasma and CSF. Our findings suggest the potential of plasma p -tau217 in the diagnosis and screening for AD, which could allow for a decreased use of invasive biomarkers in the future.

Background: It has been suggested that high stride-to-stride variability (STV) is a reflection of gait instability. However, both low and high STV has been shown in fallers and in nonfallers; therefore, the interpretation of STV of spatiotemporal gait parameters remains difficult. Thus, we sought to characterize and compare STV of spatial and temporal stride parameters among young and older healthy adults, and to determine the extent to which opposite results in STV could provide similar implications in terms of gait stability. Methods: Mean values of coefficients of variation of spatiotemporal gait parameters were collected from 30 young adults (14 men and 16 women; mean age 28.1 ± 6.0 years) and 33 older adults (2 men and 31 women; mean age 74.4 ± 7.1 years) walking at self-chosen normal walking speed over a GAITRite® System. Results: An age-related increase in STV was only observed with stride width (p = 0.012), whereas increased stride length and stance time variability in older adults were related to decreased walking speed (p = 0.006 and p = 0.018). In addition, both low and high STV was found in both groups of subjects and the highest value was observed for stride width (p < 0.001). Conclusion: The two main implications of the present results are that decreased walking speed should be taken into account when exploring age-related effects on gait variability, and that both low and high spatiotemporal STV may reflect gait stability in healthy adults.

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 (β = −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 (β = 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.

[...]direct and indirect costs of the post-COVID-19 condition have been recently estimated to range from US$140 to US$600 billion annually [4]. [...]one of the most prevalent and disabling symptoms of the post-COVID-19 condition is “brain fog”, reflecting the persistence of neurocognitive symptoms such as confusion, forgetfulness, a lack of focus and mental clarity, and fatigue [1,5]. [...]a recent European study showed that families with cognitive impairment require a 48% higher household income to achieve a normal living standard [8]. [...]the economic burden would not only be limited to direct and indirect costs for the patient, but also to their closer family circle, thus exacarbating the economic toxicity on society and highlighting the significant impact that cognitive disorders have on daily life. [...]based on patient testimonials, a gap exists between empirical evidence of post-COVID-19 symptoms and the knowledge of health care professionals and economists.