Cognitive profiles of patients with mild cognitive impairment or dementia in Alzheimer's or Parkinson's disease.

BACKGROUND: Alzheimer's disease (AD) and Parkinson's disease (PD) are associated with severe cognitive decline, but it is still unclear to what extent they become functionally more similar over time. METHODS: We compared amnestic mild cognitively impaired (aMCI; n = 29) patients to mild cognitively impaired (MCI) PD patients (n = 25), and patients with AD (n = 34) to patients with PD dementia (PDD; n = 15) with respect to cognitive functioning and mood. RESULTS: aMCI patients were impaired in episodic memory, while MCI PD patients showed deficits in visuoconstruction and attention. AD and PDD patients showed comparable deficits on tests for language, attention and visuoconstruction. However, unlike PDD patients but similar to aMCI patients, AD patients showed a characteristic memory impairment, especially commission errors on recognition tasks, whereas PDD patients scored higher on the depressive mood questionnaire. CONCLUSIONS: In advanced stages of both diseases, the pattern of functional deficits associated with parietal and temporal lobe functions (attention, visuoconstruction and language) is similar. However, specific differences, already present in the early stage (recognition errors in AD, associated with mediobasal temporal lobe functioning, and depressed mood in PDD, associated with non-motor basal ganglia loops), are also observed in the late stage.

Neural correlates of stimulus response and stimulus outcome shifting in healthy participants and MS patients.

INTRODUCTION: Adaptation to changing situations can be mediated by two strategies: (1) Evaluation of a response and (2) Evaluation of outcome values in relation to objects. Previous studies indicate that response shifting is associated with a network comprising the left frontal cortex and parietal cortex connected by the superior longitudinal fascicle, whereas outcome evaluation is associated with a network consisting of the orbitofrontal cortex, amygdala and uncinate fascicle. However, these studies rarely compared both kinds of adaptation directly and existing fMRI studies with healthy subjects are not informative about the role of the two fiber systems. METHODS: We analyzed stimulus response shifting and stimulus outcome shifting in two studies, one fMRI-study on healthy participants and one study on patients with MS involving structural MRI (Diffusion Tensor Imaging, Voxel Based Morphometry, Ventricular volumetry). Two tasks were used, identical in presentation but different in instruction, controlling for effects of lower level processing. In the SRS task, participants had to perform a "Go" or "NoGo" response depending on a stimulus change: if the stimulus remained the same, they had to continue with the former type of response, if it changed they had to adapt their response pattern. In the SOS task they had to perform a "Go" response only if the presented stimulus corresponded to that of an internal alternating series. RESULTS: fMRI findings showed that SRS is related to a bilateral parietal-premotor network. In the left hemisphere the prefrontal cortex was also involved. SOS was lateralized to the right hemisphere, particularly to the anterior temporal pole and amygdala, and the inferior parietal cortex. MS patients impaired on this task suffered from lesions in the right uncinate fascicle and showed an enlarged right frontal lateral ventricle. CONCLUSION: With physically identical tasks, a functional neuronal segregation can be demonstrated for stimulus response shifting (bilateral activations with a focus in the left prefrontal cortex) and stimulus outcome shifting (right anterior temporal lobe and right supramarginal gyrus).

Intracranial venous pressure is normal in patients with multiple sclerosis.

Chronic cerebrospinal venous insufficiency (CCSVI) has been postulated as a cause for multiple sclerosis (MS). Venous pressure assessments have not been made. Intracranial venous pressure was assessed using ophthalmodynamometry in 29 MS patients and compared with 28 healthy controls and 19 cases with elevated intracranial pressure (ICP). MS and control subjects had normal venous pressures (mean 15.5 resp. 15.1 cmHg). Only cases with intracranial pressure pathology had elevated venous pressures (mean 28.8 cmHg). There is no evidence of an increased intracranial venous pressure in MS patients.

Efficacy of an executive function intervention programme in MS: a placebo-controlled and pseudo-randomized trial.

We evaluated a rehabilitation programme for executive deficits in multiple sclerosis patients by comparing outcome scores of a cognitive intervention group (CIG; n = 11) with those of a placebo group (n = 14) and an untreated group (n = 15). Executive functioning and verbal learning improved significantly more in the CIG. The treatment effect on verbal learning was still present at 1-year follow-up. Baseline brain atrophy, quantified by the brain parenchymal fraction, was associated with treatment effects for one aspect of executive functioning. Consequently, cognitive intervention may be beneficial and baseline brain atrophy has some predictive value in determining treatment outcome for executive functioning.

The association between California Verbal Learning Test performance and fibre impairment in multiple sclerosis: evidence from diffusion tensor imaging.

The California Verbal Learning Test (CVLT) is recognized as a standard clinical tool for assessing episodic memory difficulties in multiple sclerosis (MS), but its neural correlates have not yet been examined in detail in this patient population. We combined neuropsychological examination and diffusion tensor imaging (DTI) analysis in a group of MS patients (N = 50) and demographically matched healthy participants (N = 20). We investigated the degree of impairment of the uncinate fascicle (UF), the superior longitudinal fascicle (SLF), the fornix (FX) and the cingulum (CG). The patients were impaired on all CVLT parameters and the DTI parameters correlated moderately with disease-related variables. Regression analyses in the complete study sample showed that CVLT learning scores correlated with impairment of the right UF. This association reached marginal significance in the patient sample. In contrast to other studies claiming retrieval deficits, our results suggest that encoding and consolidation deficits may play a major role in verbal memory impairments in MS. The findings also provide evidence for an association between degree of myelination of prefrontal fibre pathways and encoding efficiency. Finally, DTI-derived measurements appear to reflect disease progression in MS. The results are discussed in light of functional MRI studies investigating compensatory brain activity during cognitive processing in MS.

Comparison of diffusion tensor-based tractography and quantified brain atrophy for analyzing demyelination and axonal loss in MS.

We combined diffusion tensor imaging (DTI) measures of the corpus callosum (CC) and the superior longitudinal fascicle (SLF) with calculation of brain atrophy in 53 patients with relapsing-remitting multiple sclerosis (MS) and 15 healthy controls, to analyze their interrelation and their correlation with disease duration and clinical impairment. The lateral ventricle volume in MS patients was increased; the fractional anisotropy in the CC was decreased as was the fiber volume. Perpendicular (in the literature also referred to as radial) diffusivity (ped), which reflects the diffusion perpendicular to the long axis of the axons within the fiber bundle, was increased in the SLF and the posterior CC, but contrary to our predictions, parallel (also called axial) diffusivity (pad) that refers to the amount of diffusion in the direction of the axon was increased, too. Brain atrophy and DTI-derived parameters were highly intercorrelated and both correlated with disease duration. Discriminant analysis showed that DTI-derived atrophy measures are superior to brain atrophy measures in classifying patients and controls. In light of our results, animal studies focusing on demyelination and axonal loss are reinterpreted.

Impaired stimulus-outcome but preserved stimulus-response shifting in young substance-dependent individuals.

Substance dependency has been related to an impairment in executive functions and to a dysfunction of the frontal cortex. In this study we developed two experimental tasks, which are physically identical, to analyze whether substance-dependent individuals are impaired in shifting response patterns (stimulus response links) or preferences (stimulus outcome links). To increase the specificity of the dependent variable, we also used two control tasks to analyze for unspecific performance deficits. We included 35 young subjects with polysubstance abuse (International Classification of Diseases, F19.2 ICD 10 diagnosis, mean age of 22 years, maximum age < 27 years) and 18 normal controls, but for a first step focused on only 22 patients and 15 age-matched controls, because we excluded all patients with an IQ below 100. The results show that the substance-dependent individuals are selectively impaired in shifting object preference (stimulus-outcome links) and not in shifting response patterns. They moreover show a higher general impulsivity as reflected in their faster responses than controls on all tasks except the stimulus-outcome task. In a second step we replicated these results by analyzing the original groups of 35 patients and 18 controls. We argue that substance-dependent subjects show an impairment only on specific executive tasks, and these tasks concern stimulus-outcome link shifting, which has been associated with the functioning of the orbitofrontal cortex, not of the lateral prefrontal cortex.