Ronan Zimmermann

Cognitive training in Parkinson disease Cognition-specific vs nonspecific computer training

Objective: In this study, we compared a cognition-specific computer-based cognitive training program with a motion-controlled computer sports game that is not cognition-specific for their ability to enhance cognitive performance in various cognitive domains in patients with Parkinson disease (PD). Methods: Patients with PD were trained with either a computer program designed to enhance cognition (CogniPlus, 19 patients) or a computer sports game with motion-capturing controllers (Nintendo Wii, 20 patients). The effect of training in 5 cognitive domains was measured by neuropsychological testing at baseline and after training. Group differences over all variables were assessed with multivariate analysis of variance, and group differences in single variables were assessed with 95% confidence intervals of mean difference. The groups were similar regarding age, sex, and educational level. Results: Patients with PD who were trained with Wii for 4 weeks performed better in attention (95% confidence interval: −1.49 to −0.11) than patients trained with CogniPlus. Conclusions: In our study, patients with PD derived at least the same degree of cognitive benefit from non–cognition-specific training involving movement as from cognition-specific computerized training. For patients with PD, game consoles may be a less expensive and more entertaining alternative to computer programs specifically designed for cognitive training. Classification of evidence: This study provides Class III evidence that, in patients with PD, cognition-specific computer-based training is not superior to a motion-controlled computer game in improving cognitive performance.

Apathy in Parkinson's disease is related to executive function, gender and age but not to depression.

Deficits in executive functions occur in up to 93% of patients with Parkinsons disease (PD). Apathy, a reduction of motivation and goal-directed behavior is an important part of the syndrome; affecting both the patients as well as their social environment. Executive functions can be subdivided into three different processes: initiation, shifting and inhibition. We examined the hypotheses, (1) that apathy in patients with Parkinsons disease is only related to initiation and not to shifting and inhibition, and (2) that depression and severity of motor signs correlate with apathy. Fifty-one non-demented patients (19 = female) with PD were evaluated for apathy, depression and executive functions. Executive function variables were summarized with an index variable according to the defined executive processes. Linear regression with stepwise elimination procedure was used to select significant predictors. The significant model (R2 = 0.41; p < 0.01) revealed influences of initiation (b = −0.79; p < 0.01), gender (b = −7.75; p < 0.01), age (b = −0.07; p < 0.05) and an age by gender interaction (b = 0.12; p < 0.01) on apathy in Parkinsons disease. Motor signs, depression and level of education did not influence the relation. These results support an association of apathy and deficits of executive function in PD. Initiation strongly correlates with apathy, whereas depression does not. We conclude, that initiation dysfunction in a patient with Parkinsons disease heralds apathy. Apathy and depression can be dissociated. Additionally, apathy is influenced by age and gender: older age correlates with apathy in men, whereas in women it seems to protect against it.

Negative symptoms in neuroleptic-naïve patients with first-episode psychosis correlate with QEEG parameters

INTRODUCTION While several studies have shown an association of QEEG band power with negative symptoms in patients with schizophrenia, this has not yet been investigated in a sample with neuroleptic-naïve first-episode patients (NNFE) up to now. From literature we hypothesized delta (0.5-4Hz) and theta (4-8Hz) power to be augmented and alpha (8-12Hz) power to be decreased with increased negative symptoms in NNFE. MATERIALS AND METHODS The sample consisted of 27 NNFE. Psychopathology was rated with the Scale for the Assessment of Negative Symptoms (SANS). EEG was recorded from 21 electrodes according to the 10/20 system. Spectral analysis was performed on mean power of 8 electrodes in seven frequency bands after artefact removal. Linear regressions were calculated with log transformed power as dependent and psychopathology as independent variable. We controlled for medication, drugs, age, sex, education and day time of EEG recording. RESULTS A positive correlation of SANS global score with power in delta and theta frequency bands could be confirmed in NNFE. In the alpha1 (8-10Hz) band we found no significant correlation with negative symptoms and in the alpha2 (10-12Hz) band there was a positive correlation with SANS (p=0.069). Beta1 (12-15Hz) power also correlated positively with SANS. DISCUSSION The present results confirm the correlation of negative symptoms with power of slow frequency bands. In addition to previous studies in chronic schizophrenia patients, the effect was shown in NNFE, which is compatible with augmented slow wave power being a marker for negative symptoms in psychosis.

Slowing of EEG background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction

Background: Slowing of the electroencephalogram (EEG) is frequent in Parkinson’s (PD) and Alzheimer’s disease (AD) and correlates with cognitive decline. As overlap pathology plays a role in the pathogenesis of dementia, it is likely that demented patients in PD show similar physiological alterations as in AD. Objective: To analyze distinctive quantitative EEG characteristics in early cognitive dysfunction in PD and AD. Methods: Forty patients (20 PD- and 20 AD patients with early cognitive impairment) and 20 normal controls (NC) were matched for gender, age, and education. Resting state EEG was recorded from 256 electrodes. Relative power spectra, median frequency (4–14 Hz), and neuropsychological outcome were compared between groups. Results: Relative theta power in left temporal region and median frequency separated the three groups significantly (p = 0.002 and p < 0.001). Relative theta power was increased and median frequency reduced in patients with both diseases compared to NC. Median frequency was higher in AD than in PD and classified groups significantly (p = 0.02). Conclusion: Increase of theta power in the left temporal region and a reduction of median frequency were associated with presence of AD or PD. PD patients are characterized by a pronounced slowing as compared to AD patients. Therefore, in both disorders EEG slowing might be a useful biomarker for beginning cognitive decline.

Power spectra for screening parkinsonian patients for mild cognitive impairment

Mild cognitive impairment in Parkinsons disease (PD‐MCI) is diagnosed based on the results of a standardized set of cognitive tests. We investigate whether quantitative EEG (qEEG) measures could identify differences between cognitively normal PD (PD‐CogNL) and PD‐MCI patients.

Quantitative EEG and apolipoprotein E-genotype improve classification of patients with suspected Alzheimer's disease

OBJECTIVE To establish a model for better identification of patients in very early stages of Alzheimers disease, AD (including patients with amnestic MCI) using high-resolution EEG and genetic data. METHODS A total of 26 patients in early stages of probable AD and 12 patients with amnestic MCI were included. Both groups were similar in age and education. All patients had a comprehensive neuropsychological examination and a high resolution EEG. Relative band power characteristics were calculated in source space (LORETA inverse solution for spectral data) and compared between groups. A logistic regression model was calculated including relative band-power at the most significant location, ApoE status, age, education and gender. RESULTS Differences in the delta band at 34 temporo-posterior source locations (p<.01) between AD and MCI groups were detected after correction for multiple comparisons. Classification slightly increased when ApoE status was added (p=.06 maximum likelihood test). Adjustment of analyses for the confounding factors age, gender and education did not alter results. CONCLUSIONS Quantitative EEG (qEEG) separates between patients with amnestic MCI and patients in early stages of probable AD. Adding information about Apo ε4 allele frequency slightly enhances diagnostic accuracy. SIGNIFICANCE qEEG may help identifying patients who are candidates for possible benefit from future disease modifying treatments.

Correlation of EEG Slowing with Cognitive Domains in Nondemented Patients with Parkinson's Disease

Background: Cognitive deficits in Parkinsons disease (PD) are heterogeneous and can be classified into cognitive domains. Quantitative EEG is related to and predictive of cognitive status in PD. In this cross-sectional study, the relationship of cognitive domains and EEG slowing in PD patients without dementia is investigated. Methods: A total of 48 patients with idiopathic PD were neuropsychologically tested. Cognitive domain scores were calculated combining Z-scores of test variables. Slowing of EEG was measured with median EEG frequency. Linear regression was used for correlational analyses and to control for confounding factors. Results: EEG median frequency was significantly correlated to cognitive performance in most domains (episodic long-term memory, rho = 0.54; overall cognitive score, rho = 0.47; fluency, rho = 0.39; attention, rho = 0.37; executive function, rho = 0.34), but not to visuospatial functions and working memory. Conclusion: Global EEG slowing is a marker for overall cognitive impairment in PD and correlates with impairment in the domains attention, executive function, verbal fluency, and episodic long-term memory, but not with working memory and visuospatial functions. These disparate effects warrant further investigations.

Can cognitive deficits facilitate differential diagnosis between at-risk mental state for psychosis and depressive disorders?

Many studies have provided evidence of cognitive deficits in individuals in an ‘At Risk Mental State’ (ARMS) for psychosis, which makes neuropsychology potentially useful in the early detection of psychosis. As depression is an important differential diagnosis in prodromal states of psychosis, the specificity of neurocognitive deficits in ARMS individuals as compared with non‐psychotic depressive disorders is investigated.

Apathy in Patients with Parkinson's Disease Correlates with Alteration of Left Fronto-Polar Electroencephalographic Connectivity

Introduction: Quantitative electroencephalography (QEEG) brain frequency and network analyses are known to differentiate between disease stages in Parkinsons disease (PD) and are possible biomarkers. They correlate with cognitive decline. Little is known about changes in brain networks in relation to apathy. Objective/Aims: To analyze changes in brain network connectivities related to apathy. Methods: 40 PD patients (14 PD with mild cognitive deficits and 26 PD with normal cognition) were included. All patients had extensive neuropsychological testing; apathy was evaluated using the apathy evaluation score (AES, median 24.5, range 18–39). Resting state EEG was recorded with 256 electrodes and analyzed using fully automated Matlab® code (TAPEEG). For estimation of the connectivities between brain regions, PLI (phase lag index) was used, enhanced by a microstates segmentation. Results: After correction for multiple comparisons, significant correlations were found for single alpha2-band connectivities with the AES (p-values < 0.05). Lower connectivities, mainly involving the left fronto-polar region, were related to higher apathy scores. Conclusions: In our sample of patients with PD, apathy correlates with a network alteration mainly involving the left fronto-polar region. This might be due to dysfunction of the cortico-basal loop, modulating motivation.

P136. Relation of EEG frequency and apathy in patients with Parkinson’s disease (PD)

Objective To examine the hypothesis that apathy in patients with PD is related to frontal and temporal changes in EEG frequencies. We expected apathy to correlate with slowing of general EEG background activity, with decrease of alpha power and with increase of theta power in frontal and temporal regions of the brain. Methods 37 non-demented patients with idiopathic PD were recruited from the Movement Disorder Outpatient Clinic Basel (age: Median 69y; from 50y to 84y; 14 females). The Apathy Evaluation Scale (AES) (Marin, 1991) in informant version (AES-I) were completed by relatives of the patients.256-channel EEGs with quantitative semi-automatic analyses were used to detect alpha total-frequencies alpha 1-, alpha 2- and theta-in frontal and temporal regions. In addition, slowing of EEG was measured with Median Peak frequency. For statistics, a general linear model with backward elimination procedure was conducted. We controlled for confounding factors: age, gender, education, severity of motor symptoms, levodopa equivalent dose, depression and cognition. Results In this sample, the patients were only slightly affected by apathy ( Median =24; from 18 to 39; cut off value: 38). The resulting model was significant ( R 2 = 0.39 ; p b =−3.74; p =0.08). Relevant variables in the resulting model were alpha total, temporal right ( b =76.493; p b =−58.37; p b =−13.07; p r =−0.40), whereas in females there was no correlation between alpha total and the number of apathy symptoms ( r =0.04). Conclusions Slowing of EEG is correlated with apathy in patients with PD. This correlation is significant even in PD patients with little or no depression. This fact helps to separate the two neuropsychiatric entities. In accordance with our hypothesis, beginning apathy in PD might be related to an alpha 1 decrease the frontal left part of the brain. In contrast, alpha total of the right hemisphere positively correlates with apathy. In addition, however, the results in male gender are consistent with our expectation, but have to be replicated in a larger sample of PD patients with more severe apathy.