Cortical Tau Aggregation Patterns associated with Apraxia in Alzheimer's Disease.

Objectives: Apraxia is a core feature of Alzheimer's disease, but the pathomechanism of this characteristic symptom is not well understood. Here, we systematically investigated apraxia profiles in a well-defined group of patients with Alzheimer's disease (AD; N=32) who additionally underwent PET imaging with the second-generation tau PET tracer [18F]PI-2620. We hypothesized that specific patterns of tau pathology might be related to apraxic deficits. Methods: Patients (N=32) with a biomarker-confirmed diagnosis of Alzheimer's disease were recruited in addition to a sample cognitively unimpaired controls (CU 1 ; N=41). Both groups underwent in-depth neuropsychological assessment of apraxia (Dementia Apraxia Screening Test; DATE and the Cologne Apraxia Screening; KAS). In addition, static PET imaging with [18F]PI-2620 was performed to assess tau pathology in the AD patients. To specifically investigate the association of apraxia with regional tau-pathology, we compared the PET-data from this group with an independent sample of amyloid-negative cognitively intact participants (CU 2; N=54) by generation of z-score-deviation maps as well as voxel- based multiple regression analyses. Results: We identified significant clusters of tau-aggregation in praxis-related regions (e.g., supramarginal gyrus, angular gyrus, temporal, parietal and occipital regions) that were associated with apraxia. These regions were similar between the two apraxia assessments. No correlations between tau-tracer uptake in primary motor cortical or subcortical brain regions and apraxia were observed. Conclusions: These results suggest that tau deposition in specific cortical brain regions may induce local neuronal dysfunction leading to a dose-dependent functional decline in praxis performance.

Chronic Hyponatremia and Brain Structure and Function Before and After Treatment.

RATIONALE & OBJECTIVE: Hyponatremia is the most common electrolyte disorder and is associated with significant morbidity and mortality. This study investigated neurocognitive impairment, brain volume, and alterations in magnetic resonance imaging (MRI)-based measures of cerebral function in patients before and after treatment for hyponatremia. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with presumed chronic hyponatremia without signs of hypo- or hypervolemia treated in the emergency department of a German tertiary-care hospital. EXPOSURE: Hyponatremia (ie, plasma sodium concentration [Na+]<125mmol/L) before and after treatment leading to [Na+]>130mmol/L. OUTCOMES: Standardized neuropsychological testing (Mini-Mental State Examination, DemTect, Trail Making Test A/B, Beck Depression Inventory, Timed Up and Go) and resting-state MRI were performed before and after treatment of hyponatremia to assess total brain and white and gray matter volumes as well as neuronal activity and its synchronization. ANALYTICAL APPROACH: Changes in outcomes after treatment for hyponatremia assessed using bootstrapped confidence intervals and Cohen d statistic. Associations between parameters were assessed using correlation analyses. RESULTS: During a 3.7-year period, 26 patients were enrolled. Complete data were available for 21 patients. Mean [Na+]s were 118.4mmol/L before treatment and 135.5mmol/L after treatment. Most measures of cognition improved significantly. Comparison of MRI studies showed a decrease in brain tissue volumes, neuronal activity, and synchronization across all gray matter after normalization of [Na+]. Volume effects were particularly prominent in the hippocampus. During hyponatremia, synchronization of neuronal activity was negatively correlated with [Na+] (r=-0.836; 95% CI, -0.979 to-0.446) and cognitive function (Mini-Mental State Examination, r=-0.523; 95% CI, -0.805 to-0.069; DemTect, r=-0.744; 95% CI, -0.951 to-0.385; and Trail Making Test A, r=0.692; 95% CI, 0.255-0.922). LIMITATIONS: Small sample size, insufficient quality of several MRI scans as a result of motion artifact. CONCLUSIONS: Resolution of hyponatremia was associated with improved cognition and reductions in brain volumes and neuronal activity. Impaired cognition during hyponatremia is closely linked to increased neuronal activity rather than to tissue volumes. Furthermore, the hippocampus appears to be particularly susceptible to hyponatremia, exhibiting pronounced changes in tissue volume. PLAIN-LANGUAGE SUMMARY: Hyponatremia is a common clinical problem, and patients often present with neurologic symptoms that are at least partially reversible. This study used neuropsychological testing and magnetic resonance imaging to examine patients during and after correction of hyponatremia. Treatment led to an improvement in patients' cognition as well as a decrease in their brain volumes, spontaneous neuronal activity, and synchronized neuronal activity between remote brain regions. Volume effects were particularly prominent in the hippocampus, an area of the brain that is important for the modulation of memory. During hyponatremia, patients with the lowest sodium concentrations had the highest levels of synchronized neuronal activity and the poorest cognitive test results.

The structure of cognitive strategies for wayfinding decisions.

Literature proposes five distinct cognitive strategies for wayfinding decisions at intersections. Our study investigates whether those strategies rely on a generalized decision-making process, on two frame-specific processes-one in an egocentric and the other in an allocentric spatial reference frame, and/or on five strategy-specific processes. Participants took six trips along a prescribed route through five virtual mazes, each designed for decision-making by a particular strategy. We found that wayfinding accuracy on trips through a given maze correlated significantly with the accuracy on trips through another maze that was designed for a different reference frame (rbetween-frames = 0.20). Correlations were not significantly higher if the other maze was designed for the same reference frame (rwithin-frames = 0.19). However, correlations between trips through the same maze were significantly higher than those between trips through different mazes that were designed for the same reference frame (rwithin-maze = 0.52). We conclude that wayfinding decisions were based on a generalized cognitive process, as well as on strategy-specific processes, while the role of frame-specific processes-if any-was relatively smaller. Thus, the well-established dichotomy of egocentric versus allocentric spatial representations did not translate into a similar, observable dichotomy of decision-making.

Improved connectivity and cognition due to cognitive stimulation in Alzheimer's disease.

Background: Due to the increasing prevalence of Alzheimer's disease (AD) and the limited efficacy of pharmacological treatment, the interest in non-pharmacological interventions, e.g., cognitive stimulation therapy (CST), to improve cognitive dysfunction and the quality of life of AD patients are on a steady rise. Objectives: Here, we examined the efficacy of a CST program specifically conceptualized for AD dementia patients and the neural mechanisms underlying cognitive or behavioral benefits of CST. Methods: Using neuropsychological tests and MRI-based measurements of functional connectivity, we examined the (neuro-) psychological status and network changes at two time points: pre vs. post-stimulation (8 to 12 weeks) in the intervention group (n = 15) who received the CST versus a no-intervention control group (n = 15). Results: After CST, we observed significant improvement in the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale, cognitive subsection (ADAS-cog), and the behavioral and psychological symptoms of dementia (BPSD) scores. These cognitive improvements were associated with an up-regulated functional connectivity between the left posterior hippocampus and the trunk of the left postcentral gyrus. Conclusion: Our data indicate that CST seems to induce short-term global cognition and behavior improvements in mild to moderate AD dementia and enhances resting-state functional connectivity in learning- and memory-associated brain regions. These convergent results prove that even in mild to moderate dementia AD, neuroplasticity can be harnessed to alleviate cognitive impairment with CST.

Fine-grained age-matching improves atrophy-based detection of mild cognitive impairment more than amyloid-negative reference subjects.

INTRODUCTION: In clinical practice, differentiating between age-related gray matter (GM) atrophy and neurodegeneration-related atrophy at early disease stages, such as mild cognitive impairment (MCI), remains challenging. We hypothesized that fined-grained adjustment for age effects and using amyloid-negative reference subjects could increase classification accuracy. METHODS: T1-weighted magnetic resonance imaging (MRI) data of 131 cognitively normal (CN) individuals and 91 patients with MCI from the Alzheimer's disease neuroimaging initiative (ADNI) characterized concerning amyloid status, as well as 19 CN individuals and 19 MCI patients from an independent validation sample were segmented, spatially normalized and analyzed in the framework of voxel-based morphometry (VBM). For each participant, statistical maps of GM atrophy were computed as the deviation from the GM of CN reference groups at the voxel level. CN reference groups composed with different degrees of age-matching, and mixed and strictly amyloid-negative CN reference groups were examined regarding their effect on the accuracy in distinguishing between CN and MCI. Furthermore, the effects of spatial smoothing and atrophy threshold were assessed. RESULTS: Approaches with a specific reference group for each age significantly outperformed all other age-adjustment strategies with a maximum area under the curve of 1.0 in the ADNI sample and 0.985 in the validation sample. Accounting for age in a regression-based approach improved classification accuracy over that of a single CN reference group in the age range of the patient sample. Using strictly amyloid-negative reference groups improved classification accuracy only when age was not considered. CONCLUSION: Our results demonstrate that VBM can differentiate between age-related and MCI-associated atrophy with high accuracy. Crucially, age-specific reference groups significantly increased accuracy, more so than regression-based approaches and using amyloid-negative reference groups.

Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer's disease.

Objective: Elevated cortisol levels have been frequently reported in Alzheimer's disease (AD) and linked to brain atrophy, especially of the hippocampus. Besides, high cortisol levels have been shown to impair memory performance and increase the risk of developing AD in healthy individuals. We investigated the associations between serum cortisol levels, hippocampal volume, gray matter volume and memory performance in healthy aging and AD. Methods: In our cross-sectional study, we analyzed the relationships between morning serum cortisol levels, verbal memory performance, hippocampal volume, and whole-brain voxel-wise gray matter volume in an independent sample of 29 healthy seniors (HS) and 29 patients along the spectrum of biomarker-based AD. Results: Cortisol levels were significantly elevated in patients with AD as compared to HS, and higher cortisol levels were correlated with worse memory performance in AD. Furthermore, higher cortisol levels were significantly associated with smaller left hippocampal volumes in HS and indirectly negatively correlated to memory function through hippocampal volume. Higher cortisol levels were further related to lower gray matter volume in the hippocampus and temporal and parietal areas in the left hemisphere in both groups. The strength of this association was similar in HS and AD. Conclusion: In AD, cortisol levels are elevated and associated with worse memory performance. Furthermore, in healthy seniors, higher cortisol levels show a detrimental relationship with brain regions typically affected by AD. Thus, increased cortisol levels seem to be indirectly linked to worse memory function even in otherwise healthy individuals. Cortisol may therefore not only serve as a biomarker of increased risk for AD, but maybe even more importantly, as an early target for preventive and therapeutic interventions.

Concordance of Intrinsic Brain Connectivity Measures Is Disrupted in Alzheimer's Disease.

Background: Recently, a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to evaluate the concordance between different rs-fMRI metrics has been proposed and has not been investigated in Alzheimer's disease (AD). Methods: 3T rs-fMRI data were obtained from healthy young controls (YC, n = 26), healthy senior controls (SC, n = 29), and AD patients (n = 35). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were analyzed, followed by the calculation of their concordance using Kendall's W for each brain voxel across time. Group differences in the concordance were compared globally, within seven intrinsic brain networks, and on a voxel-by-voxel basis with covariates of age, sex, head motion, and gray matter volume. Results: The global concordance was lowest in AD among the three groups, with similar differences for the single metrics. When comparing AD to SC, reductions of concordance were detected in each of the investigated networks apart from the limbic network. For SC in comparison to YC, lower global concordance without any network-level difference was observed. Voxel-wise analyses revealed lower concordance in the right middle temporal gyrus in AD compared to SC and lower concordance in the left middle frontal gyrus in SC compared to YC. Lower fALFF were observed in the right angular gyrus in AD in comparison to SC, but ReHo and DC showed no group differences. Conclusions: The concordance of resting-state measures differentiates AD from healthy aging and may represent a novel imaging marker in AD.

Multidomain cognitive impairment in non-hospitalized patients with the post-COVID-19 syndrome: results from a prospective monocentric cohort.

BACKGROUND: A fraction of patients with asymptomatic to mild/moderate acute COVID-19 disease report cognitive deficits as part of the post-COVID-19 syndrome. This study aimed to assess the neuropsychological profile of these patients. METHODS: Assessment at baseline (three months or more following acute COVID-19) of a monocentric prospective cohort of patients with post-COVID-19 syndrome. Multidomain neuropsychological tests were performed, and questionnaires on depression, anxiety, fatigue, sleep, and general health status were administered. RESULTS: Of the 58 patients screened, six were excluded due to possible alternative causes of cognitive impairment (major depression, neurodegenerative disease). Of the remaining 52 individuals, only one had a below-threshold screening result on Mini-Mental State Examination, and 13 scored below the cut-off on Montreal Cognitive Assessment. Extended neuropsychological testing revealed a neurocognitive disorder (NCD) in 31 (59.6%) participants with minor NCD in the majority of cases (n = 26). In patients with NCD, the cognitive domains learning/memory and executive functions were impaired in 60.7%, complex attention in 51.6%, language in 35.5%, and perceptual-motor function in 29.0%. Cognitive profiles were associated with daytime sleepiness but not with depression, anxiety, sleep quality, total general health status, or fatigue. CONCLUSION: Neurocognitive impairment can be confirmed in around 60% of individuals with self-reported deficits as part of post-COVID-19 syndrome following a mild acute COVID-19 disease course. Notably, screening tests cannot reliably detect this dysfunction. Standard psychiatric assessments showed no association with cognitive profiles. Longitudinal studies are needed to further evaluate the course of neurocognitive deficits and clarify pathophysiology.

[The Cost of Early Diagnosis of Cognitive Decline in German Memory Clinics]. / Kosten der Diagnostik kognitiver Störungen in deutschen Gedächtnisambulanzen.

Dementias are expensive diseases: the net annual cost in European healthcare is about € 28.000 per case with a strong stage dependency, of which medical care accounts for about 19%. Diagnostic costs, on the other hand, account for only a small proportion of the total costs. With changes in the guidelines, biomarker tests are becoming increasingly important. At present, the concrete economic impact of biomarker-based diagnosis is largely unknown. To determine the actual costs of diagnostic procedures based on guidelines, we conducted a survey among the members of the German Memory Clinic Network (DNG). From 15 expert centres, the staff engagement time for all procedures was collected. Based on the individual engagement times of the different professions, the total of personnel costs for diagnostics was calculated using current gross personnel costs. The total sum of diagnostic costs (personnel plus procedures) was calculated for three different scenarios e. g. € 633,97 for diagnostics without biomarkers, € 1.214,90 for diagnostics with CSF biomarkers and € 4.740,58 € for diagnostics with FDG- plus Amyloid-PET. In addition, the actual diagnostic costs of the current practice in expert memory clinics were estimated, taking into account personnel costs, costs for the different procedures and the frequency of their use across all patients. This results in total average costs of € 1.394,43 per case as the mean across all centres (personnel costs € 351,72, costs for diagnostic procedures € 1.042,71). The results show that state-of-the-art diagnosis of dementia and pre-dementia states, such as mild cognitive impairment (MCI) requires financial resources, which are currently not fully reimbursed in Germany. The need for a biomarker-based etiological diagnosis of dementia and pre-dementia states will increase, due to availability of disease-modifying treatments. Therefore, the current gap of reimbursement must be filled by new models of compensation.

Decreased Efficiency of Between-Network Dynamics During Early Memory Consolidation With Aging.

Aging is associated with memory decline and progressive disabilities in the activities of daily living. These deficits have a significant impact on the quality of life of the aging population and lead to a tremendous burden on societies and health care systems. Understanding the mechanisms underlying aging-related memory decline is likely to inform the development of compensatory strategies promoting independence in old age. Research on aging-related memory decline has mainly focused on encoding and retrieval. However, some findings suggest that memory deficits may at least partly be due to impaired consolidation. To date, it remains elusive whether aging-related memory decline results from defective consolidation. This study examined age effects on consolidation-related neural mechanisms and their susceptibility to interference using functional magnetic resonance imaging data from 13 younger (20-30 years, 8 female) and 16 older (49-75 years, 5 female) healthy participants. fMRI was performed before and during a memory paradigm comprised of encoding, consolidation, and retrieval phases. Consolidation was variously challenged: (1) control (no manipulation), (2) interference (repeated stimulus presentation with interfering information), and (3) reminder condition (repeated presentation without interfering information). We analyzed the fractional amplitude of low-frequency fluctuations (fALFF) to compare brain activity changes from pre- to post-encoding rest. In the control condition, fALFF was decreased in the left supramarginal gyrus, right middle temporal gyrus, and left precuneus but increased in parts of the occipital and inferior temporal cortex. Connectivity analyses between fALFF-derived seeds and network ROIs revealed an aging-related decrease in the efficiency of functional connectivity (FC) within the ventral stream network and between salience, default mode, and central executive networks during consolidation. Moreover, our results indicate increased interference susceptibility in older individuals with dynamics between salience and default mode networks as a neurophysiological correlate. Conclusively, aging-related memory decline is partly caused by inefficient consolidation. Memory consolidation requires a complex interplay between large-scale brain networks, which qualitatively decreases with age.

[Acute Aortic Dissection: A Life-Threatening Disease Also in Neurological Emergency Medicine]. / Akute Aortendissektion: Ein lebensbedrohlicher Notfall auch in der neurologischen Notfallmedizin.

Acute aortic dissection is rare but life-threatening. The symptoms depend on the localization and reduced perfusion of the downstream organs or limbs and are therefore variable. Neurological symptoms may occur that do not immediately lead to a diagnosis and thus delay the necessary therapy. Knowing the early symptoms and warning signs of aortic dissection is therefore also crucial in neurological emergency care for quickly identifying the affected patients and for providing acute therapy. A misdiagnosis with delayed initiation of therapy can significantly worsen the patient's outcome. This study aims to establish a standardized diagnostic and therapeutic algorithm for suspected acute aortic dissection in neurological emergency care. Close interdisciplinary cooperation is mandatory.

Alzheimer's Disease Plasma Biomarkers Distinguish Clinical Diagnostic Groups in Memory Clinic Patients.

INTRODUCTION: Several recent research studies show high performance of blood biomarkers to identify Alzheimer's disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed. METHODS: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Aß42), amyloid-beta40 (Aß40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed. RESULTS: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Aß42/Aß40 (H(2) = 7.50, p = 0.02) and pTau181/Aß42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Aß42 and an SCD versus MCI difference for Aß42/Aß40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Aß42, Aß40, and NFL concentrations. CONCLUSION: Plasma pTau181 and NFL, as well as the ratios Aß42/Aß40 and pTau181/Aß42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies.

[Brain Stimulation for the Treatment of Dementia]. / Stimulationsverfahren zur Behandlung von Demenzen.

Due to the increasing number of cases of Alzheimer's disease and the relatively moderate success with the available symptomatic and causal pharmacological therapies, there is a considerable need to explore non-pharmacological treatment options. In the field of non-invasive brain stimulation (NIBS), various methods have been investigated, particularly transcranial magnetic stimulation and transcranial electrical stimulation. In addition, deep brain stimulation (DBS) is currently being researched as an innovative method for targeted neuromodulation. Both non-invasive and invasive approaches aim to modulate neuronal activity and improve cognitive-mnestic functions. Secondary mechanisms such as long-term potentiation in NIBS or neurogenesis in DBS could also achieve long-term positive effects. Preclinical and clinical studies have already shown promising results in patients in early stages of Alzheimer's disease. However, inconsistent study and stimulation protocols and small sample sizes make it difficult to assess efficacy. Further research is warranted to enable the use of non-invasive or invasive neuromodulatory approaches in clinical practice in the near future.

IGNITE Status Epilepticus Survey: A Nationwide Interrogation about the Current Management of Status Epilepticus in Germany.

We aimed to evaluate the current management of status epilepticus (SE) in intensive care units (ICUs) in Germany, depending on the different hospital levels of care and the ICU specialty. We performed a nationwide web-based anonymized survey, including all German ICUs registered with the German Society for Neurointensive and Emergency Care (Deutsche Gesellschaft für Neurointensiv- und Notfallmedizin; DGNI). The response rate was 83/232 (36%). Continuous EEG monitoring (cEEG) was available in 86% of ICUs. Regular written cEEG reports were obtained in only 50%. Drug management was homogeneous with a general consensus regarding substance order: benzodiazepines-anticonvulsants-sedatives. Thereunder first choice substances were lorazepam (90%), levetiracetam (91%), and propofol (73%). Data suggest that network structures for super-refractory SE are not permeable, as 75% did not transfer SE patients. Our survey provides "real world data" concerning the current management of SE in Germany. Uniform standards in the implementation of cEEG could help further improve the overall quality. Initial therapy management is standardized. For super-refractory SE, a concentration of highly specialized centers establishing network structures analogous to neurovascular diseases seems desirable to apply rescue therapies with low evidence carefully, ideally collecting data on this rare condition in registries and clinical trials.

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.

COVID-19 and Intracranial Hemorrhage: A Multicenter Case Series, Systematic Review and Pooled Analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). RESULTS: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. CONCLUSION: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.

Methodological Considerations for Setting Up Deep Brain Stimulation Studies for New Indications.

Deep brain stimulation (DBS) is a neurosurgical treatment with a growing range of indications. The number of clinical studies is expanding because of DBS for new indications and efforts to improve DBS for existing indications. To date, various methods have been used to perform DBS studies. Designing a clinical intervention study with active implantable medical devices has specific challenges while expanding patient treatment. This paper provides an overview of the key aspects that are essential for setting up a DBS study.

Age and Anterior Basal Forebrain Volume Predict the Cholinergic Deficit in Patients with Mild Cognitive Impairment due to Alzheimer's Disease.

BACKGROUND: Early and severe neuronal loss in the cholinergic basal forebrain is observed in Alzheimer's disease (AD). To date, cholinomimetics play a central role in the symptomatic treatment of AD dementia. Although basic research indicates that a cholinergic deficit is present in AD before dementia, the efficacy of cholinomimetics in mild cognitive impairment (MCI) remains controversial. Predictors of cholinergic impairment could guide individualized therapy. OBJECTIVE: To investigate if the extent of the cholinergic deficit, measured using positron emission tomography (PET) and the tracer 11C-N-methyl-4-piperidyl acetate (MP4A), could be predicted from the volume of cholinergic basal forebrain nuclei in non-demented AD patients. METHODS: Seventeen patients with a high likelihood of MCI due to AD and 18 age-matched cognitively healthy adults underwent MRI-scanning. Basal forebrain volume was assessed using voxel-based morphometry and a cytoarchitectonic atlas of cholinergic nuclei. Cortical acetylcholinesterase (AChE) activity was measured using MP4A-PET. RESULTS: Cortical AChE activity and nucleus basalis of Meynert (Ch4 area) volume were significantly decreased in MCI. The extent of the cholinergic deficit varied considerably across patients. Greater volumes of anterior basal forebrain nuclei (Ch1/2 area) and younger age (Spearman's rho (17) â€Š= -0.596, 95% -CI [-0.905, -0.119] and 0.593, 95% -CI [0.092, 0.863])) were associated with a greater cholinergic deficit. CONCLUSION: Data suggest that less atrophy of the Ch1/2 area and younger age are associated with a more significant cholinergic deficit in MCI due to AD. Further investigations are warranted to determine if the individual response to cholinomimetics can be inferred from these measures.

Cerebrospinal Fluid Analysis Post-COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection.

This study was undertaken to assess whether SARS-CoV-2 causes a persistent central nervous system infection. SARS-CoV-2-specific antibody index and SARS-CoV-2 RNA were studied in cerebrospinal fluid following COVID-19. Cerebrospinal fluid was assessed between days 1 and 30 (n = 12), between days 31 and 90 (n = 8), or later than 90 days (post-COVID-19, n = 20) after COVID-19 diagnosis. SARS-CoV-2 RNA was absent in all patients, and in none of the 20 patients with post-COVID-19 syndrome were intrathecally produced anti-SARS-CoV-2 antibodies detected. The absence of evidence of SARS-CoV-2 in cerebrospinal fluid argues against a persistent central nervous system infection as a cause of neurological or neuropsychiatric post-COVID-19 syndrome. ANN NEUROL 2022;91:150-157.