Cognitive screening in Parkinson's disease: Comparison of the Parkinson Neuropsychometric Dementia Assessment (PANDA) with 3 other short scales.

BACKGROUND: Cognitive screening is crucial in Parkinson's disease (PD). However, there is still a lack of short tools in French. In this study, we aimed to compare the Parkinson Neuropsychometric Dementia Assessment (PANDA) with the Mini Mental Parkinson (MMP), the Mini Mental State Examination (MMSE) and the Clock Test in French-speaking patients. We also aimed to propose cut-off scores for cognitive impairment and dementia for the French language version of the PANDA. METHOD: Fifty-one patients with PD took the PANDA, the MMSE, the MMP, and the Clock Test. They also underwent extensive neuropsychological testing by a neuropsychologist who was blinded to the above-mentioned screening test results. Patients were classified as either having normal cognition (n=15), mild cognitive impairment (n=20) or dementia (n=16). RESULTS: When compared with the three other screening tools, the PANDA exhibited the highest area under the curve (AUC) for both cognitive disorders and dementia. Using the cut-off scores proposed for the German version, the PANDA had 94% specificity and 100% sensitivity for dementia and 100% and 72%, respectively for cognitive disorders. CONCLUSIONS: In our study, the PANDA exhibited a higher discriminative power than the three other tests in detecting cognitive disorders and dementia. In PD patients, the PANDA should thus be considered for the detection of cognitive impairment in routine clinical practice.

[Value and acceptance of risk assessment for Alzheimer's disease]. / Wert und Akzeptanz einer Alzheimer-Risikodiagnostik.

BACKGROUND: It is quite common that people suffering from cognitive impairment only visit a doctor when the symptoms have already reached an advanced stage. This is often due to a fear of Alzheimer's disease or a dread of exhausting diagnostic procedures and exposure of personal details; however, an early diagnosis and therapy increases the chance of preserving the quality of life for a longer period of time. OBJECTIVES: Evaluation of a risk assessment for Alzheimer's disease by magnetic resonance imaging (MRI) with respect to the acceptance and value by participants. METHODS: In this prospective preventive study 106 subjects between the age of 39 and 89 years (median age 68 years) with general risk factors were included and underwent a risk assessment for Alzheimer's disease by standard MRI of the brain using a 1 T open MRI with subsequent hippocampal volumetry. Participants were stratified into two distinct subgroups according to the individual hippocampal atrophy status, one with elevated and the other with reduced risk. All participants were thoroughly interviewed regarding anxieties and mental well-being before and after the risk assessment. RESULTS: As expected, participants with a reduced risk had a significant improvement in well-being and a reduction of fears and worries after the examination. Neither a significant deterioration of the mental situation nor an increase of fears and worries was found for participants with an elevated risk. Of the participants 90% stated that MRI-based risk stratification generated positive perspectives for the future. The assessment revealed a high acceptance by most of the participants (94%). CONCLUSION: An MRI-based risk assessment is beneficial to the patient's quality of life and as a low threshold approach may induce more individuals with concerns to take advantage of an early diagnosis of Alzheimer's disease.

[DemTect 40- and DemTect 80+: New scoring routines for these age groups]. / DemTect 40- und DemTect 80+: Neue Auswertungsroutinen für diese Altersgruppen.

The DemTect, a frequently used cognitive screening tool for the German-speaking population, has been proven to be age-, but not education-dependent. To date, scoring routines for persons under and over 60 years of age have been available. In order to describe the age-effect more specifically, the DemTect was administered to persons under 40 (n = 105; median 33 years [18 - 39]) and over 80 years of age [n = 68; median 83 years [80 - 93}). After transformation of the raw scores, which are based on the mean and standard deviation of the respective reference group, an adequate attribution of scores could be achieved and no differences between the groups can be observed in the total score or the subtest scores. The median of the transformed total score was 16 [5 ­ 18] for the younger and 15 [5 ­ 18] for the older age group. The new scoring routines supplement the scoring procedures of the DemTect for these age groups.

Inhibition of cardiac leptin expression after infarction reduces subsequent dysfunction.

Leptin is known to exert cardiodepressive effects and to induce left ventricular (LV) remodelling. Nevertheless, the autocrine and/or paracrine activities of this adipokine in the context of post-infarct dysfunction and remodelling have not yet been elucidated. Therefore, we have investigated the evolution of myocardial leptin expression following myocardial infarction (MI) and evaluated the consequences of specific cardiac leptin inhibition on subsequent LV dysfunction. Anaesthetized rats were subjected to temporary coronary occlusion. An antisense oligodesoxynucleotide (AS ODN) directed against leptin mRNA was injected intramyocardially along the border of the infarct 5 days after surgery. Cardiac morphometry and function were monitored by echocardiography over 11 weeks following MI. Production of myocardial leptin and pro-inflammatory cytokines interleukin (IL)-1ß and IL-6 were assessed by ELISA. Our results show that (1) cardiac leptin level peaks 7 days after reperfused MI; (2) intramyocardial injection of leptin-AS ODN reduces early IL-1ß and IL-6 overexpression and markedly protects contractile function. In conclusion, our findings demonstrate that cardiac leptin expression after MI could contribute to the evolution towards heart failure through autocrine and/or paracrine actions. The detrimental effect of leptin could be mediated by pro-inflammatory cytokines such as IL-1ß and IL-6. Our data could constitute the basis of new therapeutic approaches aimed to improve post-MI outcome.

Cognitive impairment in patients with a schizoaffective disorder: a comparison with bipolar patients in euthymia.

OBJECTIVES: Several studies have shown persistent neurocognitive impairment in patients with a bipolar affective disorder (BD) even in euthymia as well as in patients with a schizoaffective disorder (SAD). The aim of our study was to compare the neuropsychological performance between these two groups. Confounding variables were controlled to enhance our understanding of cognitive dysfunction in both BD and SAD. METHODS: Several domains of neurocognitive function, executive function, memory, attention, concentration and perceptuomotor function were examined in 28 euthymic SAD patients and 32 BD patients by using a neuropsychological test battery. The Hamilton Depression Rating Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to evaluate the patients' clinical status. Data analysis was performed by using a multivariate analysis of covariance (ANCOVA/MANCOVA). RESULTS: Euthymic SAD patients showed greater cognitive impairment than euthymic BD patients in the tested domains including declarative memory and attention. Putative significant group differences concerning cognitive flexibility vanished when controlled for demographic and clinical variables. Age and medication were robust predictors to cognitive performance of both SAD and BD patients. CONCLUSIONS: Our results point out the worse cognitive outcome of SAD compared to BD patients in remission. Remarkably, the variance is higher for some of the test results between the groups than within each group, this being discussed in light of the contradictive concept of SAD.

[DemTect-B: A parallel test version to the cognitive screening instrument DemTect-A]. / DemTect-B: ein Aquivalenztest zum kognitiven Screening DemTect-A.

BACKGROUND: Cognitive screening methods are useful, although non-exclusive instruments in dementia diagnosis. One such screening is the DemTect-A, which was introduced in Germany in 2000 and has since found widespread use. In the form of the DemTect-B an equivalent test for the DemTect-A is presented. Due to its identical level of difficulty, the DemTect-B is also suitable for follow-up investigations. No other screening test in German-speaking countries has a parallel version. METHODS: 80 control subjects with a mean age of 65 years (SD = 0.83, 46 women, 34 men) participated in the investigation. To test for equivalence, Dem-Tect-A and DemTect-B were offered in randomised order. With all the control subjects, the CDR (Clinical Dementia Rating Scale) has been carried out to exclude cognitive impairment. The structure of the DemTect-B is nearly identical to that of the DemTect, only the semantic fluency task "supermarket" has been replaced with an animal naming task in the B version. For this task, a separate conversion had to be calculated. Upon completion of this transformation, the total test values did not differ on a statistically significant level. CONCLUSION: The DemTect-B is a replication of the DemTect-A and both can be mutually interchanged. It is applied especially in the course of examinations and is a useful tool to identify even patients with mild dementia and mild cognitive impairment.

Factors influencing patient satisfaction with the first diagnostic consultation in multiple sclerosis: a Swiss Multiple Sclerosis Registry (SMSR) study.

BACKGROUND: Patient satisfaction is predictive of adherence, malpractice litigation and doctor-switching. OBJECTIVE: To investigate which factors of the first diagnostic consultation (FDC) influence patient satisfaction and which topics persons with multiple sclerosis (PwMS) thought were missing. METHODS: Using retrospective patient-reported data of the Swiss Multiple Sclerosis Registry from PwMS with relapsing disease onset, we fitted ordered logistic regression models on satisfaction with FDC, with socio-demographic and FDC features as explanatory factors. RESULTS: 386 PwMS diagnosed after 1995 were included. Good satisfaction with the FDC was associated with a conversation more than 20 min [multivariable odds ratio, 95% confidence interval 3.9 (2.42; 6.27)], covering many topics [1.35 (1.19; 1.54) per additional topic], the presence of a significant others [1.74 (1.03; 2.94) ], and shared decision making [3.39 (1.74; 6.59)]. Not receiving a specific diagnosis was main driver for low satisfaction [0.29 (0.15; 0.55)]. Main missing topics concerned long-term consequences (reported by 6.7%), psychological aspects (6.2%) and how to obtain support and further information (5.2%). CONCLUSIONS: A conversation of more than 20 min covering many MS relevant topics, a clear communication of the diagnosis, the presence of a close relative or significant other, as well as shared decision making enhanced patient satisfaction with the FDC. ClinicalTrials.gov Identifier: NCT02980640.

The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue.

Fatigue symptoms are reported by a majority of patients with multiple sclerosis (MS). Reliable assessment, however, is a demanding issue as the symptoms are experienced subjectively and as objective assessment strategies are missing. The objective of this study was to develop and validate a new tool, the Fatigue Scale for Motor and Cognitive Functions (FSMC), for the assessment of MS-related cognitive and motor fatigue. A total of 309 MS patients and 147 healthy controls were included into the validation study. The FSMC was tested against several external criteria (e.g. cognition, motivation, personality and other fatigue scales). The item-analysis and validation procedure showed that the FSMC is highly sensitive and specific in detecting fatigued MS patients, that both subscales significantly differentiated between patients and controls (p < 0.01), and that internal consistency (Cronbach's alpha alpha > 0.91) as well as test-retest reliability (r > 0.80) were high. Cut-off values were determined to classify patients as mildly, moderately or severely fatigued. In conclusion, the FSMC is a new scale that has undergone validation based on a large sample of patients and that provides differential quantification and graduation of cognitive and motor fatigue.

Cognitive decline in multiple sclerosis: impact of topographic lesion distribution on differential cognitive deficit patterns.

BACKGROUND: Multiple sclerosis (MS) is often accompanied by cognitive dysfunction. A negative correlation between cerebral lesion load and atrophy and cognitive performance has been pointed out almost consistently. Further, the distribution of lesions might be critical for the emergence of specific patterns of cognitive deficits. OBJECTIVE: The current study evaluated the significance of total lesion area (TLA) and central atrophy for the prediction of general cognitive dysfunction and tested for a correspondence between lesion topography and specific cognitive deficit patterns. METHODS: Thirty-seven patients with MS underwent neuropsychological assessment and magnetic resonance imaging. Lesion burden and central atrophy were quantified. Patients were classified into three groups by means of individual lesion topography (punctiform lesions/periventricular lesions/confluencing lesions in both periventricular and extra-periventricular regions). RESULTS: TLA was significantly related to 7 cognitive variables, whereas third ventricle width was significantly associated with 20 cognitive parameters. The three groups differed significantly in their performances on tasks concerning alertness, mental speed, and memory function. CONCLUSION: Third ventricle width as a straight-forward measure of central atrophy proved to be of substantial predictive value for cognitive dysfunction, whereas total lesion load played only a minor role. Periventricular located lesions were significantly related to decreased psychomotor speed, whereas equally distributed cerebral lesion load did not. These findings support the idea that periventricular lesions have a determinant impact on cognition in patients with MS.

The Multiple Sclerosis Inventory of Cognition for Adolescents (MUSICADO): A brief screening instrument to assess cognitive dysfunction, fatigue and loss of health-related quality of life in pediatric-onset multiple sclerosis.

OBJECTIVE: Screening for cognitive impairment (CI), fatigue and also Health-related quality of life (HRQoL) in patients with pediatric-onset multiple sclerosis (POMS) is of utmost importance in clinical practice. The aim of this study was to establish a new and validated pediatric screening tool "MUSICADO" that is easy to use and time economical. METHODS: 106 patients with POMS aged 12-18 years and 210 healthy controls (HCs) stratified for age and education underwent neuropsychological testing including a screening test "Multiple Sclerosis Inventory of Cognition" for adults and 8 standardized cognitive tests and established scales to assess fatigue and HRQoL. RESULTS: The phonemic verbal fluency task (RWT "s-words"), the Trail Making Test A (TMT-A), and the Digit Span Forward discriminated significantly between patients and HCs (p = 0.000, respectively) and showed the highest proportion of test failure in patients (24.5%, 17.9%; 15.1%, respectively). Therefore, they were put together to form the cognitive part of the "MUSICADO". After applying a scoring algorithm with balanced weighting of the subtests and age and education correction and a cut-off score for impairment, 35.8% of patients were categorized to be cognitively impaired (specificity: 88.6%). Fatigue was detected in 37.1% of the patients (specificity: 94.0%) and loss of HRQoL in 41.8% (specificity 95.7%) with the screening version, respectively. CONCLUSION: The MUSICADO is a newly designed brief and easy to use screening test to help to early identify CI, fatigue, and loss of HRQoL in patients with POMS as cut scores are provided for all three items. Further studies will have to show its usability in independent samples of patients with POMS.

Dynamics of microsatellite divergence under stepwise mutation and proportional slippage/point mutation models.

Recently Kruglyak, Durrett, Schug, and Aquadro showed that microsatellite equilibrium distributions can result from a balance between polymerase slippage and point mutations. Here, we introduce an elaboration of their model that keeps track of all parts of a perfect repeat and a simplification that ignores point mutations. We develop a detailed mathematical theory for these models that exhibits properties of microsatellite distributions, such as positive skewness of allele lengths, that are consistent with data but are inconsistent with the predictions of the stepwise mutation model. We use our theoretical results to analyze the successes and failures of the genetic distances (delta(mu))(2) and D(SW) when used to date four divergences: African vs. non-African human populations, humans vs. chimpanzees, Drosophila melanogaster vs. D. simulans, and sheep vs. cattle. The influence of point mutations explains some of the problems with the last two examples, as does the fact that these genetic distances have large stochastic variance. However, we find that these two features are not enough to explain the problems of dating the human-chimpanzee split. One possible explanation of this phenomenon is that long microsatellites have a mutational bias that favors contractions over expansions.

Left hemispheric neuronal heterotopia: a PET, MRI, EEG, and neuropsychological investigation of a university student.

A 21-year-old left-handed medical student had a prominent unilateral cerebral cortical malformation due to an ontogenetic migration disorder. We performed neuropsychological studies, EEG, T1- and T2-weighted and proton-density MRI, and positron emission tomography (PET) (under both the resting condition and neuropsychological activation). Neuropsychological testing revealed normal intelligence and generally normal memory functioning but selective deficits in tests of verbal fluency and spatial-figural relationships. Proton-density and T2-weighted MRI revealed extensive left cortical heterotopia that included parts of the Wernicke area. PET under the resting condition revealed a small interhemispheric difference with slightly reduced glucose metabolism in the left temporoparietal cortical zone. An activation PET (with the patient performing a verbal fluency test) resulted in a normal overall increase in metabolism but marked deviations in cortical areas. The highest activity changes were in the Broca and Wernicke areas of the right hemisphere, and there was very little activation in those regions of the left hemisphere that were expected to respond well to the activation--the temporal, parietal, and temporo-occipital cortical zones. We conclude that there can be large compensations for unilateral heterotopia.

Two-dimensional echocardiographic recognition of complications of cardiac invasive procedures.

Two-dimensional echocardiography allowed prompt recognition of a major complication of a cardiac invasive procedure in 6 patients. In 5 cases, a preinvasive echocardiographic study was available for comparison. In 1 patient with perforation of the ventricular septum by a temporary pacemaker, the catheter was visualized as it passed through the ventricular septum, with the tip located against the left ventricular posterolateral wall. In another patient, the intimal flap caused by aortic dissection after left-sided heart catheterization was clearly visualized. In 2 patients with hemopericardium secondary to cardiac perforation during right-sided cardiac catheterization, 2-dimensional echocardiography revealed pericardial effusion not noted in studies performed before the invasive procedure. Two patients in whom hemopericardium occurred from injury by the pericardiocentesis needle also were studied by 2-dimensional echocardiography. Postpericardiocentesis images revealed new intrapericardial abnormalities (a thrombus-like mass and fibrinous strands) not present in the echocardiographic studies performed before pericardiocentesis. Real-time 2-dimensional echocardiography appears to be a good tool in the recognition of the emergencies secondary to cardiac invasive procedures.

The amygdala's contribution to memory--a study on two patients with Urbach-Wiethe disease.

The consequences of primary amygdaloid damage on memory performance are described in terms of neuropsychological, CT, MRI and PET results of two patients, a brother and a sister. Both had circumscribed, bilaterally symmetrical damage confined to the amygdaloid region, while the hippocampal formation and other brain structures were intact. PET-imaging furthermore revealed an overall decrease in glucose metabolism which was particularly apparent at the cingular and thalamic levels. Although neither patient was amnesic, both showed memory impairments in selective tests. In one patient these impairments were more pronounced and they were accompanied by marked affective-emotional fluctuations. Our results suggest that the amygdaloid region is a bottle-neck structure that confers an affective flavour to memories, thereby enhancing the probability of their long term storage.

Fornix damage and memory. A case report.

The role of the fornix for episodic memory processing is still a matter of controversy. A juvenile patient of average post-surgical intelligence with fornical damage due to tumor removal is described. The fornix was damaged bilaterally at the level of the fornical columns. The patient thereafter suffered major anterograde amnesia which was most pronounced in tests using long delays (e.g., in the delayed recall index of the revised Wechsler Memory Scale). Amnesia was a prominent on the verbal as on the nonverbal level. Attention, concentration and short term memory abilities were preserved. Cognitive flexibility, procedural memory and priming were principally unimpaired. There was no evidence of retrograde amnesia. It is concluded that the fornix constitutes a major link between the three memory interfaces (medial diencephalon, medial temporal lobe, basal forebrain) and that its bilateral rupture anterior to the thalamic level may lead to lasting anterograde amnesia.

Retrograde amnesia for world knowledge and preserved memory for autobiographic events. A case report.

A patient (PC) with severe and chronic retrograde amnesia for world knowledge (tested with famous events and famous faces), but unimpaired autobiographical memory is described. The 64-year-old man had traumatic brain injury four years prior to the present evaluation. Current brain imaging showed principally damage involving the infero-lateral prefrontal and the lateral temporal regions of the left-hemisphere. PC was of average intelligence, had no depression and only minor language problems, but manifested some additional anterograde memory deficits and performed subaverage in various frontal lobe-sensitive tests. Patient PC represents one of the very few cases with a preserved retrograde episodic and an impaired retrograde knowledge system, showing a dissociation between preserved retrieval of autobiographical events and amnesia for nonpersonal famous events. It is hypothesized that the sparing of autobiographical memories can be linked to the integrity of the right frontal and temporo-polar cortices.