Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms.

While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = -0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.

Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.

[Neuropsychological disorders of memory]. / Neuropsychologische Störungen des Gedächtnisses.

This article provides an introduction to the neuropsychology of human memory. The terms short-term memory, working memory, episodic memory, semantic and procedural memory are defined and the anatomical correlates of these various memory systems are presented. Additionally, a brief introduction to the methods for neuropsychological research on human memory is given together with advice on the neuropsychological diagnostics and therapy.

Amyloid imaging for differential diagnosis of dementia: incremental value compared to clinical diagnosis and [18F]FDG PET.

PURPOSE: Cerebral beta-amyloid and regional glucose metabolism assessed by positron emission tomography (PET) are used as diagnostic biomarkers for Alzheimer's disease (AD). The present study validates the incremental diagnostic value of amyloid PET in addition to clinical diagnosis and [18F]FDG PET in a real-life memory clinic population. METHODS: Of 138 consecutive patients with cognitive impairment who received combined [18F]FDG and [11C]PIB PET, 84 were diagnosed with major neurocognitive disorder (DSM-5) and included. Baseline clinical and [18F]FDG PET diagnoses were independently established with and without access to amyloid PET results and were dichotomized into AD or non-AD disorders. The incremental value of amyloid PET was evaluated in terms of: (1) the change in clinical and [18F]FDG PET diagnoses, (2) the change in agreement between clinical and [18F]FDG PET diagnoses, and (3) diagnostic accuracy using an interdisciplinary consensus diagnosis after an extended follow-up (2.4 ± 1.3 years after PET) as the reference. RESULTS: After disclosure of the amyloid PET results, clinical and [18F]FDG PET diagnoses changed in 23% and 18% of patients, respectively, and agreement between both ratings increased from 62% to 86% (p < 0.001). The accuracy of clinical and [18F]FDG PET diagnoses improved from 71% to 89% (p < 0.01) and from 76% to 94% (p < 0.001), respectively. The additional value of amyloid PET was rather uniform in relation to age at onset and consistency with appropriate use criteria. CONCLUSION: Amyloid PET provides significant incremental diagnostic value beyond clinical and [18F]FDG PET diagnoses of AD. Given the high diagnostic accuracy of combined clinical and amyloid PET assessment, further studies are needed to clarify the role of an additional [18F]FDG PET scan in these patients.

Distinct Contributions of Dorsal and Ventral Streams to Imitation of Tool-Use and Communicative Gestures.

Imitation of tool-use gestures (transitive; e.g., hammering) and communicative emblems (intransitive; e.g., waving goodbye) is frequently impaired after left-hemispheric lesions. We aimed 1) to identify lesions related to deficient transitive or intransitive gestures, 2) to delineate regions associated with distinct error types (e.g., hand configuration, kinematics), and 3) to compare imitation to previous data on pantomimed and actual tool use. Of note, 156 patients (64.3 ± 14.6 years; 56 female) with first-ever left-hemispheric ischemic stroke were prospectively examined 4.8 ± 2.0 days after symptom onset. Lesions were delineated on magnetic resonance imaging scans for voxel-based lesion-symptom mapping. First, while inferior-parietal lesions affected both gesture types, specific associations emerged between intransitive gesture deficits and anterior temporal damage and between transitive gesture deficits and premotor and occipito-parietal lesions. Second, impaired hand configurations were related to anterior intraparietal damage, hand/wrist-orientation errors to premotor lesions, and kinematic errors to inferior-parietal/occipito-temporal lesions. Third, premotor lesions impacted more on transitive imitation compared with actual tool use, pantomimed and actual tool use were more susceptible to lesioned insular cortex and subjacent white matter. In summary, transitive and intransitive gestures differentially rely on ventro-dorsal and ventral streams due to higher demands on temporo-spatial processing (transitive) or stronger reliance on semantic information (intransitive), respectively.

Amyloid load but not regional glucose metabolism predicts conversion to Alzheimer's dementia in a memory clinic population.

PURPOSE: The value of imaging regional glucose metabolism with [18F]FDG PET for the prediction of progression from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. The predictive value of imaging with [18F]FDG PET was therefore tested and compared with that of imaging beta-amyloid load with [11C]PIB PET in the same memory clinic population of MCI patients. METHODS: Thirty-nine patients with MCI who had undergone [18F]FDG as well as [11C]PIB PET were identified from a single-centre clinical registry. [18F]FDG and [11C]PIB PET images were rated as positive or negative for the presence of regional hypometabolism typical of AD and beta-amyloid deposition, respectively. Raters were blinded to the clinical information. Patients were followed clinically for 2.7 ± 1.2 years after PET. Cox proportional hazards models, adjusted for age and sex, were used to test the predictive value of [18F]FDG PET, [11C]PIB PET, and both in combination. RESULTS: [18F]FDG PET did not significantly predict conversion to AD (p > 0.1). By contrast, models including [11C]PIB PET only (p < 0.05) or both [18F]FDG and [11C]PIB PET (p < 0.05) significantly predicted conversion to AD. The hazard ratio for AD in patients with a positive [11C]PIB scan was 10.2 (95% confidence interval 1.3-78.1). The results were confirmed by analysis of semiquantitative measures using normalized [18F]FDG uptake and [11C]PIB standardized uptake value ratios in AD-typical regions as continuous predictors. CONCLUSION: In contrast to [11C]PIB PET, [18F]FDG PET did not predict conversion from MCI to AD in this clinical patient sample. Therefore, amyloid PET should be preferred for individual prediction and patient counselling in clinical practice.

Do all visual deficits cause pure alexia? Dissociations between visual processing and reading suggest "no".

Pure alexia is a deficit of reading affecting the ability to process a word's letters in parallel. Instead, a slow, effortful letter-by-letter reading strategy is employed. It has been claimed that a visual impairment caused the reading impairment. The present study compares visual processing and word reading of a patient with severe visuospatial deficits due to probable posterior cortical atrophy (PCA) to two patients with pure alexia. A double dissociation emerged between visual processing and word reading: The participant with PCA was severely impaired in all visual tasks but read fluently while the patients with pure alexia read slowly but exhibited better preserved visual processing. It is concluded that a visual impairment does not inevitably lead to pure alexia, and that this syndrome is more plausibly conceived of as an orthographic deficit. In addition, the PCA patient's hypometabolism was assessed, and the interaction of the dorsal and ventral visual stream in word reading is discussed.

Componential Network for the Recognition of Tool-Associated Actions: Evidence from Voxel-based Lesion-Symptom Mapping in Acute Stroke Patients.

The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively.

Frequency and Chunking in Derived Words: A Parametric fMRI Study.

In usage-based linguistic theories, the assumption that high-frequency language strings are mentally represented as unitary chunks has been invoked to account for a wide range of phenomena. However, neurocognitive evidence in support of this assumption is still lacking. In line with Gestalt psychological assumptions, we propose that a language string qualifies as a chunk if the following two conditions are simultaneously satisfied: The perception of the whole string does not involve strong activation of its individual component parts, but the component parts in isolation strongly evoke the whole. Against this background, we explore the relationship between different frequency metrics and the chunk status of derived words (e.g., "government," "worthless") in a masked visual priming experiment with two conditions of interest. One condition investigates "whole-to-part" priming (worthless-WORTH), whereas the other one analyzes "part-to-whole" priming (tear-TEARLESS). Both conditions combine mixed-effects regression analyses of lexical decision RTs with a parametric fMRI design. Relative frequency (the frequency of the whole word relative to that of its onset-embedded part) emerges as the only frequency metric to correlate with chunk status in behavioral terms. The fMRI results show that relative frequency modulates activity in regions that have been related to morphological (de)composition or general task performance difficulty (notably left inferior frontal areas) and in regions associated with competition between whole, undecomposed words (right inferior frontal areas). We conclude that relative frequency affects early stages of processing, thereby supporting the usage-based concept of frequency-induced chunks.

A formal analysis of alexia in persistent aura and a comparison to acquired pure alexia.

A patient is reported with reversible pure alexia in the context of migraine with aura. Following previous, anecdotal reports, the present study is the first to formally assess word reading, writing, and other linguistic and visual processing and to compare these to a patient with stroke-related pure alexia. The reading impairment, suggestive of letter-by-letter reading, was observed across 7 days but had remitted at a 3-month follow-up. The deficit also affected recognition of letters, suggesting a functional impairment at the level of letter recognition, not just word reading. It went along with reversible abnormalities in diffusion-weighted and fluid-attenuated inversion recovery imaging in areas known to be involved in word reading.

Differential Roles of Ventral and Dorsal Streams for Conceptual and Production-Related Components of Tool Use in Acute Stroke Patients.

Impaired tool use despite preserved basic motor functions occurs after stroke in the context of apraxia, a cognitive motor disorder. To elucidate the neuroanatomical underpinnings of different tool use deficits, prospective behavioral assessments of 136 acute left-hemisphere stroke patients were combined with lesion delineation on magnetic resonance imaging (MRI) images for voxel-based lesion-symptom mapping. Deficits affecting both the selection of the appropriate recipient for a given tool (ToolSelect, e.g., choosing the nail for the hammer), and the performance of the typical tool-associated action (ToolUse, e.g., hammering in the nail) were associated with ventro-dorsal stream lesions, particularly within inferior parietal lobule. However, ToolSelect compared with ToolUse deficits were specifically related to damage within ventral stream regions including anterior temporal lobe. Additional retrospective error dichotomization based on the videotaped performances of ToolUse revealed that spatio-temporal errors (movement errors) were mainly caused by inferior parietal damage adjacent to the intraparietal sulcus while content errors, that is, perplexity, unrecognizable, or semantically incorrect movements, resulted from lesions within supramarginal gyrus and superior temporal lobe. In summary, our results suggest that in the use of tools, conceptual and production-related aspects can be differentiated and are implemented in anatomically distinct streams.

Asymmetries of amyloid-ß burden and neuronal dysfunction are positively correlated in Alzheimer's disease.

Clinical Alzheimer's disease affects both cerebral hemispheres to a similar degree in clinically typical cases. However, in atypical variants like logopenic progressive aphasia, neurodegeneration often presents asymmetrically. Yet, no in vivo imaging study has investigated whether lateralized neurodegeneration corresponds to lateralized amyloid-ß burden. Therefore, using combined (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography, we explored whether asymmetric amyloid-ß deposition in Alzheimer's disease is associated with asymmetric hypometabolism and clinical symptoms. From our database of patients who underwent positron emission tomography with both (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose (n = 132), we included all amyloid-positive patients with prodromal or mild-to-moderate Alzheimer's disease (n = 69). The relationship between (11)C-Pittsburgh compound B binding potential and (18)F-fluorodeoxyglucose uptake was assessed in atlas-based regions of interest covering the entire cerebral cortex. Lateralizations of amyloid-ß and hypometabolism were tested for associations with each other and with type and severity of cognitive symptoms. Positive correlations between asymmetries of Pittsburgh compound B binding potential and hypometabolism were detected in 6 of 25 regions (angular gyrus, middle frontal gyrus, middle occipital gyrus, superior parietal gyrus, inferior and middle temporal gyrus), i.e. hypometabolism was more pronounced on the side of greater amyloid-ß deposition (range: r = 0.41 to 0.53, all P < 0.001). Stronger leftward asymmetry of amyloid-ß deposition was associated with more severe language impairment (P < 0.05), and stronger rightward asymmetry with more severe visuospatial impairment (at trend level, P = 0.073). Similarly, patients with predominance of language deficits showed more left-lateralized amyloid-ß burden and hypometabolism than patients with predominant visuospatial impairment and vice versa in several cortical regions. Associations between amyloid-ß deposition and hypometabolism or cognitive impairment were predominantly observed in brain regions with high amyloid-ß load. The relationship between asymmetries of amyloid-ß deposition and hypometabolism in cortical regions with high amyloid-ß load is in line with the detrimental effect of amyloid-ß burden on neuronal function. Asymmetries were also concordant with lateralized cognitive symptoms, indicating their clinical relevance.

Neural bases of imitation and pantomime in acute stroke patients: distinct streams for praxis.

Apraxia is a cognitive disorder of skilled movements that characteristically affects the ability to imitate meaningless gestures, or to pantomime the use of tools. Despite substantial research, the neural underpinnings of imitation and pantomime have remained debated. An influential model states that higher motor functions are supported by different processing streams. A dorso-dorsal stream may mediate movements based on physical object properties, like reaching or grasping, whereas skilled tool use or pantomime rely on action representations stored within a ventro-dorsal stream. However, given variable results of past studies, the role of the two streams for imitation of meaningless gestures has remained uncertain, and the importance of the ventro-dorsal stream for pantomime of tool use has been questioned. To clarify the involvement of ventral and dorsal streams in imitation and pantomime, we performed voxel-based lesion-symptom mapping in a sample of 96 consecutive left-hemisphere stroke patients (mean age ± SD, 63.4 ± 14.8 years, 56 male). Patients were examined in the acute phase after ischaemic stroke (after a mean of 5.3, maximum 10 days) to avoid interference of brain reorganization with a reliable lesion-symptom mapping as best as possible. Patients were asked to imitate 20 meaningless hand and finger postures, and to pantomime the use of 14 common tools depicted as line drawings. Following the distinction between movement engrams and action semantics, pantomime errors were characterized as either movement or content errors, respectively. Whereas movement errors referred to incorrect spatio-temporal features of overall recognizable movements, content errors reflected an inability to associate tools with their prototypical actions. Both imitation and pantomime deficits were associated with lesions within the lateral occipitotemporal cortex, posterior inferior parietal lobule, posterior intraparietal sulcus and superior parietal lobule. However, the areas specifically related to the dorso-dorsal stream, i.e. posterior intraparietal sulcus and superior parietal lobule, were more strongly associated with imitation. Conversely, in contrast to imitation, pantomime deficits were associated with ventro-dorsal regions such as the supramarginal gyrus, as well as brain structures counted to the ventral stream, such as the extreme capsule. Ventral stream involvement was especially clear for content errors which were related to anterior temporal damage. However, movement errors were not consistently associated with a specific lesion location. In summary, our results indicate that imitation mainly relies on the dorso-dorsal stream for visuo-motor conversion and on-line movement control. Conversely, pantomime additionally requires ventro-dorsal and ventral streams for access to stored action engrams and retrieval of tool-action relationships.

Fast word reading in pure alexia: "fast, yet serial".

Pure alexia is a severe impairment of word reading in which individuals process letters serially with a pronounced length effect. Yet, there is considerable variation in the performance of alexic readers with generally very slow, but also occasionally fast responses, an observation addressed rarely in previous reports. It has been suggested that "fast" responses in pure alexia reflect residual parallel letter processing or that they may even be subserved by an independent reading system. Four experiments assessed fast and slow reading in a participant (DN) with pure alexia. Two behavioral experiments investigated frequency, neighborhood, and length effects in forced fast reading. Two further experiments measured eye movements when DN was forced to read quickly, or could respond faster because words were easier to process. Taken together, there was little support for the proposal that "qualitatively different" mechanisms or reading strategies underlie both types of responses in DN. Instead, fast responses are argued to be generated by the same serial-reading strategy.

Invariant natural killer T (iNKT) cells prevent autoimmunity, but induce pulmonary inflammation in cystic fibrosis.

BACKGROUND/AIMS: Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition. METHODS: We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung. RESULTS: Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17(+) iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs. CONCLUSION: Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation.

Morphological-compound dysgraphia in an aphasic patient: "A wild write through the lexicon".

We describe the case of a dysgraphic aphasic individual--S.G.W.--who, in writing to dictation, produced high rates of formally related errors consisting of both lexical substitutions and what we call morphological-compound errors involving legal or illegal combinations of morphemes. These errors were produced in the context of a minimal number of semantic errors. We could exclude problems with phonological discrimination and phonological short-term memory. We also excluded rapid decay of lexical information and/or weak activation of word forms and letter representations since S.G.W.'s spelling showed no effect of delay and no consistent length effects, but, instead, paradoxical complexity effects with segmental, lexical, and morphological errors that were more complex than the target. The case of S.G.W. strongly resembles that of another dysgraphic individual reported in the literature--D.W.--suggesting that this pattern of errors can be replicated across patients. In particular, both patients show unusual errors resulting in the production of neologistic compounds (e.g., "bed button" in response to "bed"). These patterns can be explained if we accept two claims: (a) Brain damage can produce both a reduction and an increase in lexical activation; and (b) there are direct connections between phonological and orthographic lexical representations (a third spelling route). We suggest that both patients are suffering from a difficulty of lexical selection resulting from excessive activation of formally related lexical representations. This hypothesis is strongly supported by S.G.W.'s worse performance in spelling to dictation than in written naming, which shows that a phonological input, activating a cohort of formally related lexical representations, increases selection difficulties.

The German version of the Oxford Cognitive Screen (D-OCS): Normative data and validation in acute stroke and a mixed neurological sample.

Given the frequency of stroke worldwide, tools for neuropsychological assessment of patients with acute stroke are needed to identify cognitive impairments, guide rehabilitation efforts and allow for a prognosis of outcome. However, requirements for assessment tools for acute cognitive deficits differ substantially from tests for chronic neuropsychological impairments and screening tools for suspected dementia. The Oxford Cognitive Screen (OCS) has been developed as a quick to administer neurocognitive screening for acute neurological patients providing information on various cognitive domains. It is available in different languages. The present study reports cut-off scores, parallel-test reliability and concurrent validity of the German version (D-OCS). Following standardized language adaptation and translation, the D-OCS was administered to 100 healthy individuals to generate cut-off scores (5th percentile). Subsequently, 88 neurological patients were assessed with both versions of the D-OCS as well as other tests to evaluate reliability and validity of the D-OCS subscales. In a further study, the D-OCS was compared to the MoCA test in 65 acute stroke patients revealing comparable sensitivity but also differences between both tools. The cut-off scores were comparable to other international versions of the OCS. Intraclass correlations were highly significant and document reliability of the D-OCS subtests. Scores on subtests correlated significantly with independent tests securing validity. Comparison with the MoCA revealed comparable sensitivity and specificity. The D-OCS is a reliable and valid assessment tool well suited for patients with acute stroke. Differences to the MoCA test are discussed.

More extensive hypometabolism and higher mortality risk in patients with right- than left-predominant neurodegeneration of the anterior temporal lobe.

BACKGROUND: Left-predominant neurodegeneration of the anterior temporal lobe (ATL) and the associated syndrome termed semantic variant primary progressive aphasia (svPPA) are well characterized. Less is known about right-predominant neurodegeneration of the ATL, which has been associated with the clinical syndrome named right temporal variant of frontotemporal dementia (rtvFTD). Here, we assessed glucose metabolism across the brain, cognitive performance, and mortality in patients with right-predominant neurodegeneration of the ATL. METHODS: Patients with predominant hypometabolism of the ATL on FDG PET (as a measure of neurodegeneration) were retrospectively identified and categorized into those with asymmetrical right, left, or symmetric bilateral involvement (N = 10, 17, and 8). We compared whole-brain, normalized regional glucose metabolism using SPM12, cognitive performance on the CERAD Neuropsychological Assessment Battery, and mortality risk (age- and sex-adjusted Cox proportional hazard model) between groups. RESULTS: Hypometabolism was most pronounced and extensive in patients with right-predominant neurodegeneration of the ATL. Beyond the right temporal lobe, right frontal and left temporal lobes were affected in these patients. Cognitive performance was similarly impaired in all three groups, with predominant naming and hippocampal-dependent memory deficits. Mortality risk was 6.1 times higher in patients with right- than left-predominant ATL neurodegeneration (p < 0.05). Median survival duration after PET was shortest in patients with right- and longest in patients with left-predominant ATL neurodegeneration (5.7 vs 8.3 years after examination). DISCUSSION: More extensive neurodegeneration and shorter survival duration in patients with right- than left-predominant neurodegeneration of the ATL might indicate that the former consult memory clinics at a later disease stage, when symptoms like naming and episodic memory deficits have already emerged. At the time of diagnosis, the shorter survival duration of patients with right- than left-predominant ATL neurodegeneration should be kept in mind when counseling patients and caregivers.

Cognitive Deficits in Parkinson's Disease Are Associated with Neuronal Dysfunction and Not White Matter Lesions.

Background: Cognitive deficits considerably contribute to the patient's burden in Parkinson's disease (PD). While cognitive decline is linked to neuronal dysfunction, the additional role of white matter lesions (WML) is discussed controversially. Objective: To investigate the influence of WML, in comparison to neuronal dysfunction, on cognitive deficits in PD. Methods: We prospectively recruited patients with PD who underwent neuropsychological assessment using the Mattis Dementia Rating Scale 2 (DRS-2) or Parkinson Neuropsychometric Dementia Assessment (PANDA) and both MRI and PET with [18F]fluorodeoxyglucose (FDG). WML-load and PD cognition-related covariance pattern (PDCP) as a measure of neuronal dysfunction were read out. Relationship between cognitive performance and rank-transformed WML was analyzed with linear regression, controlling for the patients' age. PDCP subject scores were investigated likewise and in a second step adjusting for age and WML load. Results: Inclusion criteria were met by 76 patients with a mean (± SD) age of 63.5 ± 9.0 years and disease duration of 10.7 ± 5.4 years. Neuropsychological testing revealed front executive and parietal deficits and a median DRS-2 score of 137 (range 119-144)/144 and PANDA score of 22 (range 3-30)/30. No association between WML and cognition was observed, whereas PDCP subject scores showed a trend-level negative correlation with the DRS-2 (P = 0.060) as well as a negative correlation with PANDA (P = 0.049) which persisted also after additional correction for WML (P = 0.039). Conclusion: The present study indicates that microangiopathic WML do not have a relevant impact on neurocognitive performance in PD whereas neuronal dysfunction does.