Although Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) show a wide clinical and neuropathologic overlap, they are differentiated according to the order and latency of cognitive and motor symptom appearance. Whether both are distinct disease entities is an ongoing controversy. Therefore, we directly compared patients with DLB and PDD with multitracer PET.PET with (18)fluorodopa (FDOPA), N-(11)C-methyl-4-piperidyl acetate (MP4A), and (18)fluorodeoxyglucose (FDG) was performed in 8 patients with PDD, 6 patients with DLB, and 9 patients with PD without dementia vs age-matched controls. Data were analyzed with voxel-based statistical parametric mapping and region of interest-based statistics.We found a reduced FDOPA uptake in the striatum and in limbic and associative prefrontal areas in all patient groups. Patients with PDD and patients with DLB showed a severe MP4A and FDG binding reduction in the neocortex with increasing signal diminution from frontal to occipital regions. Significant differences between PDD and DLB were not found in any of the radioligands used. Patients with PD without dementia had a mild cholinergic deficit and no FDG reductions vs controls.Patients with dementia with Lewy bodies and Parkinson disease dementia share the same dopaminergic and cholinergic deficit profile in the brain and seem to represent 2 sides of the same coin in a continuum of Lewy body diseases. Cholinergic deficits seem to be crucial for the development of dementia in addition to motor symptoms. The spatial congruence of cholinergic deficits and energy hypometabolism argues for cortical deafferentation due to the degeneration of projection fibers from the basal forebrain.
Objectives Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia. The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. Methods Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. Results Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). Conclusion The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.
Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to activate energy metabolism in the target region and directly connected basal ganglia (BG) output nuclei in Parkinson's disease (PD).1 Active electrode poles for maximal clinical benefit in STN-DBS were located to the upper and lateral border of the STN in the near of fiber tracks passing through the zona incerta. In this study, we intended to investigate effects of acute DBS on BG activity in patients with intra- and extranuclear electrode location using 18-FDG positron emission tomography (PET).
Background: The nonmotor symptom spectrum of Parkinson’s disease (PD) includes progressive cognitive decline mainly in late stages of the disease. The aim of this study was to map the patterns of altered structural connectivity of patients with PD with different cognitive profiles ranging from cognitively unimpaired to PD-associated dementia. Methods: Diffusion tensor imaging and neuropsychological data from the observational multicentre LANDSCAPE study were analyzed. A total of 134 patients with PD with normal cognitive function (56 PD-N), mild cognitive impairment (67 PD-MCI), and dementia (11 PD-D) as well as 72 healthy controls were subjected to whole-brain-based fractional anisotropy mapping and covariance analysis with cognitive performance measures. Results: Structural data indicated subtle changes in the corpus callosum and thalamic radiation in PD-N, whereas severe white matter impairment was observed in both PD-MCI and PD-D patients including anterior and inferior fronto-occipital, uncinate, insular cortices, superior longitudinal fasciculi, corona radiata, and the body of the corpus callosum. These regional alterations were demonstrated for PD-MCI and were more pronounced in PD-D. The pattern of involved regions was significantly correlated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) total score. Conclusions: The findings in PD-N suggest impaired cross-hemispherical white matter connectivity that can apparently be compensated for. More pronounced involvement of the corpus callosum as demonstrated for PD-MCI together with affection of fronto-parieto-temporal structural connectivity seems to lead to gradual disruption of cognition-related cortico-cortical networks and to be associated with the onset of overt cognitive deficits. The increase of regional white matter damage appears to be associated with the development of PD-associated dementia.
