Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort.

OBJECTIVE: Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. METHOD: Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. RESULTS: The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. CONCLUSIONS: Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

Monocytosis in the acute phase of SARS-CoV-2 infection predicts the presence of anosognosia for cognitive deficits in the chronic phase.

Reduced awareness of neuropsychological disorders (i.e., anosognosia) is a striking symptom of post-COVID-19 condition. Some leukocyte markers in the acute phase may predict the presence of anosognosia in the chronic phase, but they have not yet been identified. This study aimed to determine whether patients with anosognosia for their memory deficits in the chronic phase presented specific leukocyte distribution in the acute phase, and if so, whether these leukocyte levels might be predictive of anosognosia. First, we compared the acute immunological data (i.e., white blood cell differentiation count) of 20 patients who displayed anosognosia 6-9 months after being infected with SARS-CoV-2 (230.25 ± 46.65 days) versus 41 patients infected with SARS-Cov-2 who did not develop anosognosia. Second, we performed an ROC analysis to evaluate the predictive value of the leukocyte markers that emerged from this comparison. Blood circulating monocytes (%) in the acute phase of SARS-CoV-2 infection were associated with long-term post-COVID-19 anosognosia. A monocyte percentage of 7.35% of the total number of leukocytes at admission seemed to predict the presence of chronic anosognosia 6-9 months after infection.

Motoric cognitive risk syndrome and incident dementia: results from a population-based prospective and observational cohort study.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR), which is the juncture of subjective cognitive complaint and slow gait speed, is a pre-dementia stage. The aims of the study are (i) to compare characteristics between individuals who have MCR defined using slow walking speed and/or increased five-times-sit-to-stand (FTSS) time as its motor component(s); and (ii) to characterize the association of MCR and its various motor components with incident dementia including Alzheimer disease and non-Alzheimer dementia in the participants of the Epidémiologie de l'Ostéoporose (EPIDOS) study. METHODS: This prospective and observational cohort study selected 651 participants recruited from the EPIDOS study in Toulouse (France). MCR was defined as the association of subjective cognitive complaint and slow gait speed and/or increased FTSS time in participants without either dementia and mobility disabilities at baseline. Individuals with dementia were prospectively diagnosed during the physical and neuropsychological assessments included in the 7-year follow-up. RESULTS: The prevalence of MCR was around 7% when using an exclusive motor criterion, either slow gait speed or increased FTSS time, and was 20.9% when MCR subgroups were pooled. MCR was positively associated with incident dementia regardless of its type, and with Alzheimer disease in the slow gait speed MCR subgroup [odds ratio (OR) > 2.18 with P ≤ 0.037] but not with non-Alzheimer dementia. No significant association between incident dementia and MCR defined using increased FTSS time was shown. CONCLUSIONS: Our findings confirm that MCR is associated with incident dementia and that slow gait speed is the appropriate motor criterion for detecting dementia risk.

Motoric cognitive risk syndrome and mortality: results from the EPIDOS cohort.

BACKGROUND AND PURPOSE: Cognitive impairment, slow walking speed and motoric cognitive risk syndrome (MCR) have separately been associated with an increased risk for mortality in the short term. The aim of the study was to examine the association of MCR and its components [i.e. subjective cognitive complaint (SCC) and slow walking speed] with short-, medium- and long-term mortality in older community-dwellers. METHODS: In all, 3778 participants from the Epidémiologie de l'Ostéoporose (EPIDOS) study were selected. MCR was defined as the combination of slow walking speed and SCC in participants without major neurocognitive disorders. Deaths were prospectively recorded using mail, phone calls, questionnaires and/or the French national death registry at 5, 10, 15 and 19 (end of follow-up period) years. RESULTS: Over the follow-up of 19 years, 80.5% (n = 3043) participants died. Slow walking speed and MCR were associated with mortality [hazard ratio (HR) 1.20 with P = 0.004 for slow walking speed and HR = 1.26 with P = 0.002 for MCR at 10 years; HR = 1.27 with P ≤ 0.001 for slow walking speed and HR = 1.22 with P = 0.001 for MCR at 15 years; HR = 1.41 with P ≤ 0.001 at 19 years for slow walking speed and MCR]. There was no association between SCC and mortality. Kaplan-Meier distributions of mortality showed that participants with MCR and slow walking speed died earlier compared to healthy participants and those with SCC (P < 0.001). CONCLUSIONS: Slow walking speed and MCR were associated with an increased risk for mortality at the medium and long term, whereas no association was found with SCC.

Age and gender differences in motor imagery.

BACKGROUND: Few studies have explored the effects of ageing and gender in the dimensions of motor imagery (MI) such as vividness (vivid images and sensations of mental movements) and timing (the duration of an imagined movement). This study aims 1) to investigate the effect of age and gender effect in vividness and timing capabilities on MI, and 2) to examine the relationship between these two dimensions of MI. METHODS: A population of 72 (47% of males) good imagers including 41 young subjects and 31 older subjects were assessed on MI vividness using the Vividness of Movement Imagery Questionnaire (VMIQ-2) and on MI timing using the performances of the real Timed Up and Go (rTUG) test and its imagined version (iTUG). The main outcome variables were the VMIQ-2 score and the delta-TUG, i.e. the difference between rTUG and iTUG. RESULTS: Mental vividness was affected by ageing with a loss of visual dominance in favor of kinesthetic imagery in older subjects compared to younger ones; however, no difference between both groups was found in timing measured by delta-TUG. Vividness capabilities were similar between men and women, but women performed better in timing. VMIQ-2 scores were not associated with delta-TUG; only gender was significantly associated with delta-TUG. CONCLUSIONS: This study revealed 1) an age-related transfer from a visual to a kinesthetic MI ability, but no impact on timing of MI; 2) a gender effect on timing with no impact on mental vividness; 3) no association between vividness and timing capabilities.

Neural correlates of gait variability in people with multiple sclerosis with fall history.

BACKGROUND AND PURPOSE: The aim was to investigate the association between step time variability and related brain structures in accordance with fall status in people with multiple sclerosis (PwMS). METHODS: The study included 225 PwMS. Whole-brain magnetic resonance imaging was performed with a high-resolution 3.0 T magnetic resonance scanner in addition to volumetric analysis based on 3D T1-weighted images using the FreeSurfer image analysis suite. Step time variability was measured with an electronic walkway. Participants were defined as 'fallers' (at least two falls during the previous year) and 'non-fallers'. RESULTS: In all, 105 PwMS were defined as fallers and had a greater step time variability compared to non-fallers [5.6% (SD = 3.4) vs. 3.4% (SD = 1.5); P = 0.001]. MS fallers exhibited a reduced volume in the left caudate and both cerebellum hemispheres compared to non-fallers. On using a linear regression analysis no association was found between gait variability and related brain structures in the total cohort and the non-fallers group. However, the analysis found an association between the left hippocampus and left putamen volumes with step time variability in the faller group: P = 0.031, 0.048, respectively, controlling for total cranial volume, walking speed, disability, age and gender. Nevertheless, according to the hierarchical regression model, the contribution of these brain measures to predict gait variability was relatively small compared to walking speed. CONCLUSIONS: An association between low left hippocampal, putamen volumes and step time variability was found in PwMS with a history of falls, suggesting that brain structural characteristics may be related to falls and increased gait variability in PwMS.

From swing to cane: Sex differences of EEG resting-state temporal patterns during maturation and aging.

While many insights on brain development and aging have been gained by studying resting-state networks with fMRI, relating these changes to cognitive functions is limited by the temporal resolution of fMRI. In order to better grasp short-lasting and dynamically changing mental activities, an increasing number of studies utilize EEG to define resting-state networks, thereby often using the concept of EEG microstates. These are brief (around 100 ms) periods of stable scalp potential fields that are influenced by cognitive states and are sensitive to neuropsychiatric diseases. Despite the rising popularity of the EEG microstate approach, information about age changes is sparse and nothing is known about sex differences. Here we investigated age and sex related changes of the temporal dynamics of EEG microstates in 179 healthy individuals (6-87 years old, 90 females, 204-channel EEG). We show strong sex-specific changes in microstate dynamics during adolescence as well as at older age. In addition, males and females differ in the duration and occurrence of specific microstates. These results are of relevance for the comparison of studies in populations of different age and sex and for the understanding of the changes in neuropsychiatric diseases.

Cognitive-motor dual-task interference modulates mediolateral dynamic stability during gait in post-stroke individuals.

Gait asymmetry and dynamic balance impairments observed in post-stroke individuals increase their risk of fall. Moreover, walking while performing a cognitive task (i.e. dual-task) disturbs the control of balance in post-stroke individuals. Here we investigated the mediolateral dynamic stability in twenty-two community-dwelling participants (12 post-strokes and 10 healthy controls) while walking in single-task (normal gait) and four different dual-tasks (cognitive-motor interference). Positions of the extrapolated center of mass and mediolateral widths of both margin of stability and base of support were extracted from 35 marker trajectories. Post-stroke participants presented larger margin of stability and base of support than controls during single-task (both p < 0.01), with a larger margin of stability on the non-paretic side than on the paretic side at ipsilateral foot-strike (p < 0.05). No significant effect of the dual-task was found between groups. In post-stroke participants, dual-task induced slight modification of the mediolateral stability strategy, as the margin of stability was not different between the two limbs at foot-strike, and significantly reduced the performance in every cognitive task. Post-stroke participants increased their dynamic stability in the frontal plane in single-task by extending their base of support and mainly relying on their non-paretic limb. Under cognitive-motor interference (dual-task), post-stroke participants prioritized dynamic stability over cognitive performance to ensure a safe locomotion. Thus, rehabilitation programs should consider both dynamic balance and dual-task training, even at a chronic delay following stroke, to reduce the risk of fall in post-stroke individuals.

Brain comorbidities in normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: This cross-sectional study aims to compare gait changes after the cerebrospinal fluid (CSF) tap test between normal pressure hydrocephalus patients with and without brain comorbidities (NPH+ and NPH- respectively) and then to identify significant contributors to a poor CSF tap test amongst individuals with NPH+. METHODS: Gait changes (during the single task and the dual task of backward counting) were quantified before and 24 h after the CSF tap test with an optoelectronic system in 52 NPH patients (77.4 ± 6.0 years; 34.6% women). Changes after the CSF tap test in stride time variability (STV, %) were our main outcome. CSF Alzheimer's disease biomarkers, cerebrovascular white matter changes assessed with brain imaging and neurodegenerative diseases with parkinsonian syndrome represented the three individual brain comorbidities. RESULTS: Brain comorbidities were frequently identified, NPH+ patients representing 40 patients of our sample (76.9%). NPH- patients improved their STV better in the single task (delta of STV = -58.6% ± 54.3% vs. -14.1% ± 62.0%; P = 0.031) and in the dual task (delta of STV =-32.2% ± 33.7% vs. 6.3% ± 58.4%; P = 0.028) after the CSF tap test than NPH+ patients. Amongst NPH+ individuals, only comorbid Alzheimer's disease was associated with STV increase (i.e. deterioration of gait) in the dual task [ß 38.4; 95% confidence interval (5.64; 71.24); P = 0.023] after the CSF tap test, whilst it was borderline in the single task [ß 35.0; 95% confidence interval (-1.97; 71.90); P = 0.063]. CONCLUSIONS: Brain comorbidities affect gait improvement after the CSF tap test in NPH patients; this influence is driven by Alzheimer's disease-related pathology.

The spectrum of pre-dementia stages: cognitive profile of motoric cognitive risk syndrome and relationship with mild cognitive impairment.

BACKGROUND AND PURPOSE: Motoric cognitive risk (MCR) syndrome is a pre-dementia syndrome. There is little information on the cognitive profile of individuals with MCR syndrome and its overlap with mild cognitive impairment (MCI) syndrome. This study aimed to examine and compare the cognitive performance of non-demented older community dwellers with and without MCR and MCI syndromes. METHODS: A total of 291 non-demented individuals were selected from the Gait and Alzheimer Interactions Tracking study, which is a cross-sectional study. All participants were referred to a memory clinic. Individuals with and without MCR were separated into those with and without MCI. Cognitive performance was measured using the scores of the Mini Mental Status Examination, Frontal Assessment Battery, Free and Cued Selective Reminding Test, Trail Making Test part A and B, and Stroop test. RESULTS: The prevalence of MCI was 40.1% and that of MCR was 18.2%, with a higher prevalence of MCI in MCR group compared with the non-MCR group (47.2% vs. 39.5%). Individuals with MCR and MCI syndromes had poorer cognitive performance in all domains compared with those without MCR (P < 0.005), except for the ratio part III: part I of the Stroop test (P = 0.345). The association between cognitive performance and MCR syndrome was worse on the Mini Mental Status Examination score [effect size, -0.57 (95% confidence interval, -1.02 to -0.12)] and Trail Making Test part B [effect size, 0.59 (95% confidence interval, 0.14-1.04)] in individuals with MCR and MCI syndromes. CONCLUSIONS: Motoric cognitive risk syndrome is associated with low global cognitive performance. Association of MCR and MCI syndromes is characterized by a worse cognitive performance.

Postural control is associated with cognition and fear of falling in patients with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting various neurological domains, such as postural control, cognition, fear of falling, depression-anxiety, and fatigue. This study examined the associations of cognitive functions, fear of falling, depression-anxiety, and fatigue with postural control in patients with MS. Postural control (sway velocity) of 63 patients with MS (age 39.0 ± 8.9 years; %female 57%; Expanded Disability Status Scale score median (interquartile range) 2.0 (1.5)) was recorded on two platforms at stable and unstable conditions. Cognition, fear of falling, depression-anxiety, and fatigue were evaluated by a comprehensive neuropsychological assessment. The associations between these domains and postural control have been measured by multivariable linear regression (adjusted for age, gender, disability, and education). In stable condition, only working memory was associated with postural control (p < 0.05). In unstable condition, working memory, executive functions, attention/processing speed, and fear of falling were associated with postural control (p < 0.05). Specific cognitive domains and fear of falling were associated with postural control in MS patients, particularly in unstable condition. These findings highlight the association of cognitive functions and fear of falling with postural control in MS.

Gait phenotype from mild cognitive impairment to moderate dementia: results from the GOOD initiative.

BACKGROUND AND PURPOSE: The differences in gait abnormalities from the earliest to the later stages of dementia and in the different subtypes of dementia have not been fully examined. This study aims to compare spatiotemporal gait parameters in cognitively healthy individuals, patients with amnestic mild cognitive impairment (MCI) and non-amnestic MCI, and patients with mild and moderate stages of Alzheimer's disease (AD) and non-Alzheimer's disease (non-AD). METHODS: Based on a cross-sectional design, 1719 participants (77.4 ± 7.3 years, 53.9% female) were recruited from cohorts from seven countries participating in the Gait, Cognition and Decline (GOOD) initiative. Mean values and coefficients of variation of spatiotemporal gait parameters were measured during normal pace walking with the GAITRite system at all sites. RESULTS: Performance of spatiotemporal gait parameters declined in parallel with the stage of cognitive decline from MCI status to moderate dementia. Gait parameters of patients with non-amnestic MCI were more disturbed compared to patients with amnestic MCI, and MCI subgroups performed better than demented patients. Patients with non-AD dementia had worse gait performance than those with AD dementia. This degradation of gait parameters was similar between mean values and coefficients of variation of spatiotemporal gait parameters in the earliest stages of cognitive decline, but different in the most advanced stages, especially in the non-AD subtypes. CONCLUSIONS: Spatiotemporal gait parameters were more disturbed in the advanced stages of dementia, and more affected in the non-AD dementias than in AD. These findings suggest that quantitative gait parameters could be used as a surrogate marker for improving the diagnosis of dementia.

Improvement in executive subfunctions following cerebrospinal fluid tap test identifies idiopathic normal pressure hydrocephalus from its mimics.

BACKGROUND AND PURPOSE: Patients with idiopathic normal pressure hydrocephalus (iNPH) present cognitive deficits that overlap with other neurological conditions such as Parkinson's disease or vascular dementia, therefore mimicking iNPH. This prospective study aimed to compare cognitive performances between iNPH and iNPH mimics before and after cerebrospinal fluid (CSF) tapping. METHODS: A total of 57 patients with suspicion of iNPH (75.84 ± 6.42 years; 39% female) were included in this study (37 iNPH and 20 iNPH mimics). Neuropsychological assessments were performed before and 24 h after CSF tapping of 40 ml. Multivariate logistic regressions were used to examine the association between iNPH and cognitive functions, adjusted for age, education, baseline cognitive assessment and disease duration. RESULTS: Both groups presented the same baseline cognitive performances. After CSF tapping, iNPH patients improved their semantic (P = 0.001) and phonemic verbal fluencies (P = 0.001), whereas iNPH mimics presented similar performances to before CSF tapping. The phonemic verbal fluency (odds ratio 1.43, 95% confidence interval 1.05; 1.96) and the Color Trails Test (odds ratio 0.10, 95% confidence interval 0.01; 0.76) improvements were the two discriminative cognitive tests that identified iNPH from iNPH mimics. CONCLUSION: Improvement in executive subfunctions after CSF tapping identified iNPH patients from other neurological conditions that mimic iNPH. These findings respond to clinical issues encountered on a daily basis and would improve the diagnostic process of iNPH.

Anti-dementia drugs-related changes in gait performance while single and dual tasking in patients with Alzheimer disease: a meta-analysis.

BACKGROUND: The effects of anti-dementia drugs on gait performance in Alzheimer disease (AD) are questionable. The objective of this meta-analysis was to examine the effects of anti-dementia drugs on the mean value and the coefficient of variation (CoV) of stride time among patients with AD while taking into account the type of drugs (i.e., acetylcholinesterase inhibitors [AChEIs] versus memantine) and the walking conditions (i.e., single versus dual-task). METHODS: An English and French Medline search was conducted in March 2015, with no limit of date, using the Medical Subject Headings terms "pharmaceutical preparations" combined with terms "Pharmaceutical preparations" OR "Therapeutic uses" OR "Drug substitution" OR "Drugs essential" OR "Drugs, Generic" OR "Psychotropic drugs" combined with "Delirium" OR "Dementia" OR "Amnestic" OR "Cognitive disorders" AND "Gait" OR "Gait Ataxia" OR "Gait disorders, Neurologic" OR "Gait apraxia". Fixed-effects meta-analyses were used to examine anti-dementia drugs-related changes in mean value and CoV of stride time. RESULTS: Of the 66 identified abstracts, 5 (7.6%) were included in the meta-analysis. Inter-group comparison of between-visit change underscored a significant decrease in CoV of stride time (P<0.004) in intervention group compared to control group, whatever the pooled analysis considered, but no significant change in the mean value (P>0.06). Intra-group changes in stride time parameters following the use of anti-dementia drugs showed a significant decrease for memantine (P<0.001) and while pooling AChEIs and memantine (P<0.001) under single task condition. Under dual task condition, only AChEIs improved significantly stride time parameters (P=0.002). CONCLUSION: Anti-dementia drugs demonstrated a significant improvement of gait performance with specific class effect depending on the walking conditions and on the type of stride time parameters considered.

Gait abnormalities in obstructive sleep apnea and impact of continuous positive airway pressure.

We aimed to determine the effect of continuous positive airway pressure (CPAP) on gait in obstructive sleep apnea (OSA) patients. Gait during single and dual tasks was recorded in 15 OSA patients at baseline and after 8 weeks of CPAP therapy. Step and stance time improved after CPAP. We showed a specific dual-task effect in the condition of verbal fluency. Eight weeks of CPAP seems to improve gait of OSA patients that are specifically disturbed by the dual task of verbal fluency.