Irena Rektorová

EFNS guidelines for the diagnosis and management of Alzheimer’s disease

Background and objectives:  In 2008 a task force was set up to develop a revision of the European Federation of the Neurological Societies (EFNS) guideline for the diagnosis and management of Alzheimer’s disease (AD) and other disorders associated with dementia, published in early 2007. The aim of this revised international guideline was to present a peer‐reviewed evidence‐based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with AD. Mild cognitive impairment and non‐Alzheimer dementias are not included in this guideline.

Pramipexole and pergolide in the treatment of depression in Parkinson's disease:a national multicentre prospective randomized study.

An 8‐month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin®) and pergolide (PRG; Permax®) as add‐on to L‐dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non‐demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinsons disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self – Rating Depression Scale by Zung were evaluated in an open‐label design.

EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia

The last version of the EFNS dementia guidelines is from 2007. In 2010, the revised guidelines for Alzheimers disease (AD) were published. The current guidelines involve the revision of the dementia syndromes outside of AD, notably vascular cognitive impairment, frontotemporal lobar degeneration, dementia with Lewy bodies, corticobasal syndrome, progressive supranuclear palsy, Parkinsons disease dementia, Huntingtons disease, prion diseases, normal‐pressure hydrocephalus, limbic encephalitis and other toxic and metabolic disorders. The aim is to present a peer‐reviewed evidence‐based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists and other specialist physicians responsible for the care of patients with dementing disorders. It represents a statement of minimum desirable standards for practice guidance.

The default mode network integrity in patients with Parkinson’s disease is levodopa equivalent dose-dependent

Disturbances in the default mode network (DMN) have been described in many neurological and psychiatric disorders including Parkinson’s disease (PD). The DMN is characterized by basal activity that increases during rest or passive visual fixation and decreases (“deactivates”) during cognitive tasks. The network is believed to be involved in cognitive processes. We examined the DMN in PD patients on dopaminergic medication with normal cognitive performance compared to age- and gender-matched healthy controls (HC) using fMRI and three methodological procedures: independent component analysis of resting-state data, analysis of deactivation during a complex visual scene-encoding task, and seed-based functional connectivity analysis. In the PD group, we also studied the effect of dopaminergic medication on the DMN integrity. We did not find any difference between the PD and HC groups in the DMN, but using the daily levodopa equivalent dose as a covariate, we observed an enhanced functional connectivity of the DMN in the posterior cingulate cortex and decreased activation in the left parahippocampal gyrus during the cognitive task. We conclude that dopaminergic therapy has a specific effect on both the DMN integrity and task-related brain activations in cognitively unimpaired PD patients, and these effects seem to be dose-dependent.

Serum inflammatory biomarkers in Parkinson's disease.

Numerous recent findings indicate the involvement of a neuroinflammatory reaction in the neurodegeneration in idiopathic Parkinsons disease (PD). We examined 29 consecutive patients with PD, ages 54-84 years, most of whom were moderately impaired (median UPDRS 19; Hoehn-Yahr 3; MMSE 28). A series of serum biomarkers were investigated, and their levels were correlated with the degree of the motor and cognitive impairment. There were no abnormalities of IL-6, acute phase proteins (C-reactive protein, serum amyloid A, alpha 1-antitrypsin, orosomucoid, ceruloplasmin, alpha 2-macroglobulin, transferrin, prealbumin) and factors of the complement system (C1q, C1-INH, C3, C4). A decrease in Mannan-binding lectin (MBL) levels was observed in six patients; an elevation of tumor necrosis factor-alpha (TNF-alpha) was found in 12 patients. No statistically significant correlation was found between the patients clinical state (neuropsychologic and motor, as expressed by UPDRS III, Hoehn-Yahr, and MMSE) and the immunomarker changes. Our results indicate that the inflammatory process may be reflected in the serum; nevertheless, further research is needed to elucidate the possible clinical implications.

Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease

We studied whether the 123I‐FP‐CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinsons disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 ± 12.7 years) underwent the 123I‐FP‐CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and 123I‐FP‐CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with 123I‐FP‐CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia.

Default Mode Network and Extrastriate Visual Resting State Network in Patients with Parkinson’s Disease Dementia

Aims: Using fMRI, we evaluated the default mode network (DMN) and the extrastriate visual resting state network (ESV-RSN) in 14 patients with Parkinson’s disease dementia (PDD) as compared with 18 patients with Parkinson’s disease (PD) without dementia and 18 healthy controls (HC). Methods: We analyzed the seed-based functional connectivity of both resting state data and deactivations during a visual complex scene-encoding task. Results: Using the posterior cingulate cortex/precuneus as a seed for the DMN analysis, we observed significant decreases of connectivity in the right inferior frontal gyrus in PDD as compared to PD and HC. Using the caudate nucleus as a seed for the ESV-RSN analysis, we found significant decreases of connectivity in the left and right inferior occipital gyrus in PDD as compared to HC. Conclusion: Differences in functional connectivity patterns between PDD and PD/HC were observed in areas known to be engaged in stimulus-driven reorienting of attention and in visual processing.

Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients

AIMS Examine whether one session of high frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) would induce any measurable cognitive changes in patients with cerebrovascular disease and mild cognitive deficits. PATIENTS AND METHOD Seven patients with cerebrovascular disease and mild executive dysfunction entered the randomised, controlled, blinded study with a crossover design. rTMS was applied either over the left DLPFC (an active stimulation site) or over the left motor cortex (MC; a control stimulation site) in one session. Each patient participated in both stimulation sessions (days 1 and 4) and the order of stimulation sites (DLPFC or MC) was randomised. A short battery of neuropsychological tests was performed by a blinded psychologist prior to and after each rTMS session. Psychomotor speed, executive function, and memory were evaluated. RESULTS The only mild but significant stimulation site-specific effect of rTMS was observed in the Stroop interference results (i.e. improvement) after the stimulation of DLPFC but not MC in comparison with the baseline scores (Wilcoxon, Z=-2.03, p=0.04). Patients improved in the digit symbols subtest of the Wechsler adult intelligence scale-revised after both rTMS sessions regardless of the stimulation site (DLPFC or MC; Z=-2.06, p=0.04 and Z=-2.06, p=0.04, respectively). There was no measurable effect of rTMS in any other neuropsychological test. CONCLUSION Our pilot study results showed that one session of the high frequency rTMS applied over the left DLPFC was safe in patients with cerebrovascular disease and mild executive deficits, and may induce measurable positive effects on executive functioning.

Vascular pathology in patients with idiopathic Parkinson's disease.

To study the impact of brain vessel pathology on the clinical status of Parkinsons disease (PD), in 57 consecutive patients the clinical and neuropsychological data were compared with clinical MRI signs of vascular impairment and with the ultrasound brain vessel investigations. There was a significant correlation between clinical and cognitive status and intimomedial thickness, which is an indicator of large vessel impairment. Cognitive status was significantly related to the pulsatility index (an indicator of small vessel impairment). This study provides evidence that subclinical vascular pathology could influence the clinical status by contributing to motor and cognitive dysfunction in PD.

Cognitive potentials in the basal ganglia—frontocortical circuits. An intracerebral recording study

We studied cognitive functions related to processing sensory and motor activities in the basal ganglia (BG), specifically in the putamen and in cortical structures forming the BG-frontocortical circuits. Intracerebral recordings were made from 160 brain sites in 32 epilepsy surgery candidates. We studied P3-like potentials in five different tests evoked by auditory and visual stimuli, and two sustained potentials that are related to cognitive activities linked with movement preparation: BP (Bereitschaftspotential) and CNV (contingent negative variation). We compared the presence of a potential with a phase reversal or an amplitude gradient to the absence of a generator. All of the studied cognitive potentials were generated in the BG; the occurrence in frontal cortical areas was more selective. The frequency of all but one potential was significantly higher in the BG than in the prefrontal and in the cingulate cortices. The P3-like potentials elicited in the oddball paradigm were also more frequent in the BG than in the motor/premotor cortex, while the occurrence of potentials elicited in motor tasks (BP, CNV, and P3-like potentials in the CNV paradigm) in the motor cortex did not significantly differ from the occurrence in the BG. The processing of motor tasks fits with the model by Alexander et al. of segregated information processing in the motor loop. A variable and task-dependent internal organisation is more probable in cognitive sensory information processing. Cognitive potentials were recorded from all over the putamen. The BG may play an integrative role in cognitive information processing.