Prevalence and trajectories of neuropsychological post-COVID-19 symptoms in initially hospitalized patients.

OBJECTIVE: To investigate the prevalence and trajectories of post-COVID-19 neuropsychological symptoms. DESIGN: Prospective longitudinal multicentre cohort study. SUBJECTS: A total of 205 patients initially hospitalized with SARS-CoV-2 (COVID-19). METHODS: Validated questionnaires were administered at 9 months (T1) and 15 months (T2) post-hospital discharge to assess fatigue, cognitive complaints, insomnia, anxiety, depression, and post-traumatic stress symptoms. RESULTS: Analyses included 184 out of 205 patients. Approximately 50% experienced high cognitive complaints at T1 and T2, while severe fatigue affected 52.5% at T1 and 55.6% at T2. Clinically relevant insomnia scores were observed in 25% of patients at both time-points. Clinically relevant anxiety scores were present in 18.3% at T1 and 16.7% at T2, depression in 15.0% at T1 and 18.9% at T2, and PTSD in 12.4% at T1 and 11.8% at T2. Most symptoms remained stable, with 59.2% of patients experiencing at least 1 persistent symptom. In addition, 31.5% of patients developed delayed-onset symptoms. CONCLUSION: Post-COVID-19 cognitive complaints and fatigue are highly prevalent and often persist. A subgroup develops delayed symptoms. Emotional distress is limited. Screening can help identify most patients experiencing long-term problems. Future research should determine risk factors for persistent and delayed onset symptoms.

A Biopsychosocial Approach to Persistent Post-COVID-19 Fatigue and Cognitive Complaints: Results of the Prospective Multicenter NeNeSCo Study.

OBJECTIVE: To evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints. DESIGN: Prospective, multicenter cohort study. SETTING: Six Dutch hospitals. PARTICIPANTS: 205 initially hospitalized (March-June 2020), confirmed patients with SARS-CoV-2, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, magnetic resonance imaging (MRI) contraindication, or severe neurologic damage post-hospital discharge (N=205). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Nine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from medical dossiers. Hierarchical regression analyses were performed on fatigue severity (Fatigue Severity Scale; FSS) and cognitive complaints (Cognitive Consequences after Intensive Care Admission; CLC-IC; dichotomized into CLC-high/low). Variable blocks: (1) Demographic and premorbid factors (sex, age, education, comorbidities), (2) Illness severity (ICU/general ward, PROMIS physical functioning [PROMIS-PF]), (3) Neuro-cognitive factors (self-reported neurological symptoms, MRI abnormalities, cognitive performance), (4) Psychological and social factors (Hospital Anxiety and Depression Scale [HADS], Utrecht Coping List, Social Support List), and (5) Fatigue or cognitive complaints. RESULTS: The final models explained 60% (FSS) and 48% (CLC-IC) variance, with most blocks (except neuro-cognitive factors for FSS) significantly contributing. Psychological and social factors accounted for 5% (FSS) and 11% (CLC-IC) unique variance. Higher FSS scores were associated with younger age (P=.01), lower PROMIS-PF (P<.001), higher HADS-Depression (P=.03), and CLC-high (P=.04). Greater odds of CLC-high were observed in individuals perceiving more social support (OR=1.07, P<.05). CONCLUSIONS: Results show that psychological and social factors add to biomedical factors in explaining persistent post-COVID-19 fatigue and cognitive complaints. Objective neuro-cognitive factors were not associated with symptoms. Findings highlight the importance of multidomain treatment, including psychosocial care, which may not target biologically-rooted symptoms directly but may reduce associated distress.

Facilitators and barriers in caring for a person with Huntington's disease: input for a remote support program.

OBJECTIVES: This study aims to provide more insight into possible barriers and facilitators caregivers of people with Huntington's disease (HD) encounter, and what their needs and wishes are regarding a remote support program. METHODS: In total, 27 persons participated in four focus group interviews. Eligible participants were caregivers (n = 19) of a person with HD, and healthcare professionals (n = 8) involved in HD care. Qualitative data were analyzed by two researchers who independently performed an inductive content analysis. RESULTS: Four major themes emerged from the data, including (1) a paradox between taking care of yourself and caring for others; (2) challenges HD caregivers face in daily life, including lack of HD awareness, taboo and shame, feelings of loneliness, concerns about heredity and children, and coping with HD symptoms; (3) facilitators in the caregiving process, including a social network, professional support, openness, talking in early phases, and daily structure; (4) needs regarding a support program. CONCLUSION: These insights will be used to develop a remote support program for HD caregivers, using a blended and self-management approach. Newly developed and tailored support should be aimed at empowering caregivers in their role and help them cope with their situation, taking into account barriers and facilitators.

The impact of deep brain stimulation of the subthalamic nucleus on facial emotion recognition in patients with Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is successful in patients with advanced Parkinson's disease (PD) but may worsen cognitive outcome, including facial emotion recognition (FER). Data-analyses on 59 consecutive PD patients with complete pre- and postoperative assessments, using a sensitive FER test, showed no changes in FER 1 year after STN-DBS surgery, both after group and individual analyses. These findings do however not exclude the impact of FER in and on itself on the outcome after STN-DBS.

Neurological and (neuro)psychological sequelae in intensive care and general ward COVID-19 survivors.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) affects the brain, leading to long-term complaints. Studies combining brain abnormalities with objective and subjective consequences are lacking. Long-term structural brain abnormalities, neurological and (neuro)psychological consequences in COVID-19 patients admitted to the intensive care unit (ICU) or general ward were investigated. The aim was to create a multidisciplinary view on the impact of severe COVID-19 on functioning and to compare long-term consequences between ICU and general ward patients. METHODS: This multicentre prospective cohort study assessed brain abnormalities (3 T magnetic resonance imaging), cognitive dysfunction (neuropsychological test battery), neurological symptoms, cognitive complaints, emotional distress and wellbeing (self-report questionnaires) in ICU and general ward (non-ICU) survivors. RESULTS: In al, 101 ICU and 104 non-ICU patients participated 8-10 months post-hospital discharge. Significantly more ICU patients exhibited cerebral microbleeds (61% vs. 32%, p < 0.001) and had higher numbers of microbleeds (p < 0.001). No group differences were found in cognitive dysfunction, neurological symptoms, cognitive complaints, emotional distress or wellbeing. The number of microbleeds did not predict cognitive dysfunction. In the complete sample, cognitive screening suggested cognitive dysfunction in 41%, and standard neuropsychological testing showed cognitive dysfunction in 12%; 62% reported ≥3 cognitive complaints. Clinically relevant scores of depression, anxiety and post-traumatic stress were found in 15%, 19% and 12%, respectively; 28% experienced insomnia and 51% severe fatigue. CONCLUSION: Coronavirus disease 2019 ICU survivors had a higher prevalence for microbleeds but not for cognitive dysfunction compared to general ward survivors. Self-reported symptoms exceeded cognitive dysfunction. Cognitive complaints, neurological symptoms and severe fatigue were frequently reported in both groups, fitting the post-COVID-19 syndrome.

Machine learning prediction of motor response after deep brain stimulation in Parkinson's disease-proof of principle in a retrospective cohort.

INTRODUCTION: Despite careful patient selection for subthalamic nucleus deep brain stimulation (STN DBS), some Parkinson's disease patients show limited improvement of motor disability. Innovative predictive analysing methods hold potential to develop a tool for clinicians that reliably predicts individual postoperative motor response, by only regarding clinical preoperative variables. The main aim of preoperative prediction would be to improve preoperative patient counselling, expectation management, and postoperative patient satisfaction. METHODS: We developed a machine learning logistic regression prediction model which generates probabilities for experiencing weak motor response one year after surgery. The model analyses preoperative variables and is trained on 89 patients using a five-fold cross-validation. Imaging and neurophysiology data are left out intentionally to ensure usability in the preoperative clinical practice. Weak responders (n = 30) were defined as patients who fail to show clinically relevant improvement on Unified Parkinson Disease Rating Scale II, III or IV. RESULTS: The model predicts weak responders with an average area under the curve of the receiver operating characteristic of 0.79 (standard deviation: 0.08), a true positive rate of 0.80 and a false positive rate of 0.24, and a diagnostic accuracy of 78%. The reported influences of individual preoperative variables are useful for clinical interpretation of the model, but cannot been interpreted separately regardless of the other variables in the model. CONCLUSION: The model's diagnostic accuracy confirms the utility of machine learning based motor response prediction based on clinical preoperative variables. After reproduction and validation in a larger and prospective cohort, this prediction model holds potential to support clinicians during preoperative patient counseling.

Feasibility of a Cognitive Training Game in Parkinson's Disease: The Randomized Parkin'Play Study.

Cognitive training (CT) shows modest positive effects on cognitive function in patients with Parkinson's disease (PD). Gamification may enhance adherence to traditional CT, but this has not been studied yet. Here, we investigated the feasibility of a gamified CT. We performed a randomized controlled trial including PD patients with mild cognitive impairment. Participants were randomly allocated to a 12-week home-based gamified CT intervention or waiting-list control group. Assessments were performed at baseline and at weeks 12 and 24. Forty-one patients were included (21 intervention and 20 waiting-list controls). Sixty-three percent of the intervention group trained >50% of the recommended sessions, while 81% voluntarily continued training after 12 weeks. After 24 weeks, 87.5% graded the game to be satisfactory. Global cognition scores improved after 24 weeks. Home-based gamified CT shows acceptable feasibility in patients with PD, and we observed preliminary indications for efficacy. Larger trials are needed to establish this efficacy.

Effectiveness of ReSET; a strategic executive treatment for executive dysfunctioning in patients with Parkinson's disease.

In this multicentre randomised controlled trial (RCT), 43 patients with Parkinson's disease (PD) were randomly allocated to either the experimental condition receiving cognitive rehabilitation including strategy training (ReSET; Strategic Executive Treatment, n = 24) or to the control condition receiving computerised repetitive practice training for attention (Cogniplus, n = 16). We expected that strategy training (ReSET) would be more effective than cognitive training (Cogniplus) in improving patients' everyday life executive functioning. Neuropsychological assessment was administered at baseline, at 2 weeks and 3-5 months post-treatment. Primary outcome measure was the Role Resumption List (RRL). Secondary outcome measures were treatment goal attainment (TGA), Dysexecutive Questionnaire (DEX), Parkinson's Disease Questionnaire (PDQ-39), Zarit Burden Interview (ZBI) and neuropsychological tests. No effects of treatment were found on the primary outcome measure and on neuropsychological tests, except for one test of attention. At 2 weeks and 3-5 months post-treatment, PD patients in both the ReSET and Cogniplus group reported a significant improvement in everyday life executive functioning, as measured with TGA and the DEX-self, with an advantage for ReSET only shortly after treatment. Given these results and that PD patients were able to adhere to these treatments despite their motor symptoms and fatigue (i.e., the drop-out rate was small), we conclude that both strategy training and cognitive training for impairments in EF might be beneficial and feasible for PD patients.

Performance and Symptom Validity Assessment in Patients with Apathy and Cognitive Impairment.

OBJECTIVE: Performance and symptom validity tests (PVTs and SVTs) measure the credibility of the assessment results. Cognitive impairment and apathy potentially interfere with validity test performance and may thus lead to an incorrect (i.e., false-positive) classification of the patient's scores as non-credible. The study aimed at examining the false-positive rate of three validity tests in patients with cognitive impairment and apathy. METHODS: A cross-sectional, comparative study was performed in 56 patients with dementia, 41 patients with mild cognitive impairment, and 41 patients with Parkinson's disease. Two PVTs - the Test of Memory Malingering (TOMM) and the Dot Counting Test (DCT) - and one SVT - the Structured Inventory of Malingered Symptomatology (SIMS) - were administered. Apathy was measured with the Apathy Evaluation Scale, and severity of cognitive impairment with the Mini Mental State Examination. RESULTS: The failure rate was 13.7% for the TOMM, 23.8% for the DCT, and 12.5% for the SIMS. Of the patients with data on all three tests (n = 105), 13.5% failed one test, 2.9% failed two tests, and none failed all three. Failing the PVTs was associated with cognitive impairment, but not with apathy. Failing the SVT was related to apathy, but not to cognitive impairment. CONCLUSIONS: In patients with cognitive impairment or apathy, failing one validity test is not uncommon. Validity tests are differentially sensitive to cognitive impairment and apathy. However, the rule that at least two validity tests should be failed to identify non-credibility seemed to ensure a high percentage of correct classification of credibility.

Grey matter abnormalities are associated only with severe cognitive decline in early stages of Parkinson's disease.

Cognitive impairment is common in Parkinson's disease (PD), yet with large heterogeneity in the range and course of deficits. In a cross-sectional study, 124 PD patients underwent extensive clinical and neuropsychological assessment as well as a 3T MRI scan of the brain. Our aim was to identify differences in grey matter volume and thickness, as well as cortical folding, across different cognitive profiles as defined through a data-driven exploratory cluster analysis of neuropsychological data. The identified cognitive groups ranged from cognitively intact patients to patients with severe deficits in all cognitive domains, whilst showing comparable levels of motor disability and disease duration. Each group was compared to the cognitively intact PD group using voxel- and vertex-based morphometry. Results revealed widespread age-related grey matter abnormalities associated with progressive worsening of cognitive functions in mild PD. When adjusted for age, significant differences were only seen between cognitively intact and severely affected PD patients and these were restricted to the right posterior cingulate and the right precuneus. Reduced cortical thickness was seen in the right inferior temporal gyrus and reduced folding in the right temporal region. As these differences were not associated with age, we assume that they are associated with underlying pathology of the cognitive decline. Given the limited involvement of grey matter differences, and the absence of differences in vascular changes across the groups, we hypothesize a more important role for white matter tract changes in cognitive decline in PD.

[Deep brain stimulation in Parkinson's disease: better balanced through consideration of the psychosocial consequences]. / Diepe hersenstimulatie bij de ziekte van Parkinson.

Deep Brain Stimulation (DBS) is an effective intervention for Parkinson's disease if drug therapy with dopaminergic medication has become insufficient. Current post-operative care focuses on optimizing the neurostimulator in combination with medication. We believe that the success rate of DBS surgery can be enhanced if more attention is paid to the (psychosocial) adjustment problems of patients and their families. Finding a new balance after surgery, in the relationship, family and work, is not easy and can be complicated by postoperative non-motor changes. Care for psychosocial adjustment may improve the quality of life and as such increase the overall outcome after surgery. We present two cases to illustrate these psychosocial adjustment problems. One case describes the impact of stimulation-related behavioural changes on relationships, while the other case describes difficulties in resuming work despite successful surgery. Psychosocial support appeared helpful for both cases to find their new balance in life.

Do-It-Yourself Gamified Cognitive Training: Viewpoint.

Cognitive decline is an important nonmotor symptom in Parkinson disease (PD). Unfortunately, very few treatment options are available. Recent research pointed to small positive effects of nonpharmacological cognitive training in PD. Most of these trainings are performed under supervision and solely computerized versions of (traditional) paper-pencil cognitive training programs, lacking rewarding gamification stimulants that could help to promote adherence. By describing 3 different self-invented ways of cognitive gaming in patients with PD, we aimed to raise awareness for the potential of gamified cognitive training in PD patients. In addition, we hoped to inspire the readers with our case descriptions, highlighting the importance of both personalization and cocreation in the development of games for health. In this viewpoint, we have presented 3 PD patients with different ages, with different disease stages, and from various backgrounds, who all used self-invented cognitive training, including elements of personalization and gamification. To indicate generalization into a larger PD population, the recruitment results from a recent cognitive game trial are added. The presented cases show similarities in terms of awareness of their cognitive decline and the ways this process could potentially be counteracted, by looking for tools to train their cognition. On the basis of the response of the recruitment procedure, there seems to be interest in gamified cognitive training in a larger PD population too. Gamification may add to traditional therapies in terms of personalization and adherence. Positive results have already been found with gamified trainings in other populations, and the cases described here suggest that PD is also an attractive area to develop and test gamified cognitive trainings. However, no results of gamified cognitive trainings in PD have been published to date. This suggests an unmet need in this area and may justify the development of gamified cognitive training and its evaluation, for which our considerations can be used.

Resting-state fMRI in Parkinson's disease patients with cognitive impairment: A meta-analysis.

BACKGROUND: Cognitive impairment is a common non-motor symptom in Parkinson's disease. So far, the underlying pathophysiology remains unclear. Several alterations in functional network connectivity have been described in Parkinson's disease patients with cognitive impairment which are probably the result of the heterogenous pathophysiology underlying this cognitive decline, including dopaminergic and cholinergic deficits. Accordingly, the reported resting-state connectivity patterns vary greatly among studies. OBJECTIVE: To evaluate the localization and magnitude of functional connectivity patterns in resting-state brain networks in Parkinson's disease patients with cognitive impairment by pooling data from available studies. METHODS: We searched PubMed, the Cochrane Library, MEDLINE, Embase and PsycINFO to identify functional MRI studies in Parkinson's disease patients with cognitive impairment. A voxel-based meta-analysis combined with quality statistics was performed, using the anisotropic effect-size version of the signed differential mapping method. RESULTS: Seventeen studies with cognitively impaired Parkinson's disease patients were included consisting of 222 Parkinson's disease patients with mild cognitive impairment, 68 patients with Parkinson's disease dementia, 289 cognitively unimpaired Parkinson's disease patients and 353 healthy controls. Parkinson's disease patients with cognitive impairment predominantly showed a reduced connectivity in specific brain regions that are part of the default mode network. CONCLUSION: Cognitive impairment in Parkinson's disease is associated with reduced connectivity in networks relevant to cognition, most prominently the default mode network. Specific alterations in functional connectivity may contribute to cognitive decline in Parkinson patients and may be a promising future biomarker.

Thalamic Deep Brain Stimulation for Refractory Tourette Syndrome: Clinical Evidence for Increasing Disbalance of Therapeutic Effects and Side Effects at Long-Term Follow-Up.

OBJECTIVE: Thalamic deep brain stimulation (DBS) is effective in reducing tics in patients with refractory Tourette syndrome at the short-term. Here, we report on the long-term outcome. MATERIALS AND METHODS: Seven patients underwent bilateral DBS between 2001 and 2008. The target was the centromedian nucleus, substantia periventricularis and nucleus ventro-oralis internus cross point of the thalamus. The effect on tics and side effects were evaluated with a variable follow-up duration of 12 to 78 months. RESULTS: Patient 1 and 2 showed good tic improvements of 81.6% (60 months) and 50% (36 months), respectively. However, side effects like reducing levels of energy and visual disturbances increased. In patient 1, the target was changed to the anterior part of the internal pallidum and patient 2 switched the stimulator permanently off. Patient 3 experiences still satisfying results with a tic improvement of 88.9% (78 months). Patient 4 and 7 showed minor tic improvements of 34% (16 months) and 9% (60 months), respectively. In both patients side effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 5 showed a tic improvement of 27.5% (12 months) and went abroad for stimulation of the external globus pallidus. Patient 6 developed cerebellar atrophy. He experienced several nonstimulation related side effects and turned the stimulator off. CONCLUSIONS: There seems to be an increasing disbalance of therapeutic effects and side effects at long-term follow-up, often leading to either switching the stimulator off or new surgery with a different neuro-anatomic target.

Theory of mind performance in Parkinson's disease is associated with motor and cognitive functions, but not with symptom lateralization.

Next to the typical motor signs, Parkinson's disease (PD) goes along with neuropsychiatric symptoms, amongst others affecting social cognition. Particularly, Theory of Mind (ToM) impairments have mostly been associated with right hemispherical brain dysfunction, so that it might prevail in patients with left dominant PD. Fourty-four PD patients, twenty-four with left and twenty with right dominant motor symptoms, engaged in the Reading the Mind in the Eyes (RME) and the Faux Pas Detection Test (FPD) to assess affective and cognitive ToM. The results were correlated with performance in further cognitive tests, and analyzed with respect to associations with the side of motor symptom dominance and severity of motor symptoms. No association of ToM performance with right hemispheric dysfunction was found. RME results were inversely correlated with motor symptom severity, while FPD performance was found to correlate with the performance in verbal fluency tasks and the overall cognitive evaluation. Affective ToM was found associated with motor symptom severity and cognitive ToM predominantly with executive function, but no effect of PD lateralization on this was identified. The results suggest that deficits in social cognition occur as a sequel of the general corticobasal pathology in PD, rather than as a result of hemisphere-specific dysfunction.

Objective Versus Subjective Measures of Executive Functions: Predictors of Participation and Quality of Life in Parkinson Disease?

OBJECTIVES: To determine whether objective (neuropsychological tests) and subjective measures (questionnaires) of executive functions (EFs) are associated in patients with Parkinson disease (PD), and to determine to what extent level of participation and quality of life (QoL) of patients with PD can be predicted by these measures of EFs. DESIGN: Correlational research design (case-control and prediction design). SETTING: Departments of neuropsychology of 3 medical centers. PARTICIPANTS: A sample (N=136) of patients with PD (n=42) and their relatives, and controls without PD (n=94). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A test battery measuring EFs. In addition, patients, their relatives, and controls completed the Dysexecutive Questionnaire, Brock Adaptive Functioning Questionnaire, and Barkley Deficits in Executive Functioning Scale - time management questionnaires measuring complaints about EFs. Participation and QoL were measured with the Impact on Participation and Autonomy scale and the Parkinson's Disease Questionnaire-39, respectively. RESULTS: Patients with PD showed impairments in EFs on objective tests and reported significantly more complaints about EFs than did controls without PD. No associations were found between patients' performances on objective and subjective measures of EFs. However, both objective and subjective measures predicted patients' level of participation. In addition, subjective measures of EFs predicted QoL in patients with PD. CONCLUSIONS: These findings show that objective and subjective measures of EFs are not interchangeable and that both approaches predict level of participation and QoL in patients with PD. However, within this context, sex needs to be taken into account.

Cognitive phenotypes in parkinson's disease differ in terms of brain-network organization and connectivity.

Cognitive deficits are common in Parkinson's disease and we suspect that dysfunctions of connected brain regions can be the source of these deficits. The aim of the present study was to investigate changes in whole-brain intrinsic functional connectivity according to differences in cognitive profiles in Parkinson's disease. 119 participants were enrolled and divided into four groups according to their cognitive phenotypes (determined by a cluster analysis): (i) 31 cognitively intact patients (G1), (ii) 31 patients with only slight mental slowing (G2), (iii) 43 patients with mild to moderate deficits mainly in executive functions (G3), (iv) 14 patients with severe deficits in all cognitive domains (G4-5). Rs-fMRI whole-brain connectivity was examined by two complementary approaches: graph theory for studying network functional organization and network-based statistics (NBS) for exploring functional connectivity amongst brain regions. After adjustment for age, duration of formal education and center of acquisition, there were significant group differences for all functional organization indexes: functional organization decreased (G1 > G2 > G3 > G4-5) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, P < 0.01) mainly concerned the ventral prefrontal, parietal, temporal and occipital cortices as well as the basal ganglia. In Parkinson's disease, brain network organization is progressively disrupted as cognitive impairment worsens, with an increasing number of altered connections between brain regions. We observed reduced connectivity in highly associative areas, even in patients with only slight mental slowing. The association of slowed mental processing with loss of connectivity between highly associative areas could be an early marker of cognitive impairment in Parkinson's disease and may contribute to the detection of prodromal forms of Parkinson's disease dementia. Hum Brain Mapp 38:1604-1621, 2017. © 2016 Wiley Periodicals, Inc.