Associations of hippocampal subfields in the progression of cognitive decline related to Parkinson's disease.

OBJECTIVE: Hippocampal atrophy has been associated with mild cognitive impairment (MCI) in Parkinson's disease (PD). However, literature on how hippocampal atrophy affects the pathophysiology of cognitive impairment in PD has been limited. Previous studies assessed the hippocampus as an entire entity instead of their individual subregions. We studied the progression of cognitive status in PD subjects over 18 in relation to hippocampal subfields atrophy. METHODS: 65 PD subjects were included. Using the MDS task force criteria, PD subjects were classified as either having no cognitive impairment (PD-NCI) or PD-MCI. We extended the study by investigating the hippocampal subfields atrophy patterns in those who converted from PD-NCI to PD-MCI (PD-converters) compared to those who remained cognitively stable (PD-stable) over 18 months. Freesurfer 6.0 was used to perform the automated segmentation of the hippocampus into thirteen subregions. RESULTS: PD-MCI showed lower baseline volumes in the left fimbria, right CA1, and right HATA; and lower global cognition scores compared to PD-NCI. Baseline right CA1 was also correlated with baseline attention. Over 18 months, decline in volumes of CA2-3 and episodic memory were also seen in PD-converters compared to PD-stable. Baseline volumes of GC-DG, right CA4, left parasubiculum, and left HATA were predictive of the conversion from PD-NCI to PD-MCI. CONCLUSION: The findings from this study add to the anatomical knowledge of hippocampal subregions in PD, allowing us to understand the unique functional contribution of each subfield. Structural changes in the hippocampus subfields could be early biomarkers to detect cognitive impairment in PD

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Progressive Supranuclear Gaze Palsy with Predominant Cerebellar Ataxia: A Case Series with Videos.

10.14802/jmd.16059J Mov Disord10287-9

Effects of Age and Gender on Hand Motion Tasks

Objective. Wearable and wireless motion sensor devices have facilitated the automated computation of speed, amplitude, and rhythm of hand motion tasks. The aim of this study is to determine if there are any biological influences on these kinematic parameters. Methods. 80 healthy subjects performed hand motion tasks twice for each hand, with movements measured using a wireless motion sensor device (Kinesia, Cleveland Medical Devices Inc., Cleveland, OH). Multivariate analyses were performed with age, gender, and height added into the model. Results. Older subjects performed poorer in finger tapping (FT) speed (r=0.593, p<0.001), hand-grasp (HG) speed (r=0.517, p<0.001), and pronation-supination (PS) speed (r=0.485, p<0.001). Men performed better in FT rhythm p<0.02, HG speed p<0.02, HG amplitude p<0.02, and HG rhythm p<0.05. Taller subjects performed better in the speed and amplitude components of FT p<0.02 and HG tasks p<0.02. After multivariate analyses, only age and gender emerged as significant independent factors influencing the speed but not the amplitude and rhythm components of hand motion tasks. Gender exerted an independent influence only on HG speed, with better performance in men p<0.05. Conclusions. Age, gender, and height are not independent factors influencing the amplitude and rhythm components of hand motion tasks. The speed component is affected by age and gender differences

Towards a sensing system for quantification of pathological tremor

International audiencePathological tremor compensatio

Kalman filtering of accelerometer and electromyography data in pathological tremor sensing system

International audienceCurrently there is a lack of objective clinical diagnosis and classification of tremor is difficult when it is subtle. Thus in previous work, a sensing system has been developed to quantify pathological tremor in human upper limb. In this paper, a Kalman filter algorithm to fuse information from accelerometers and surface electromyography is proposed. As the ground truth, an optical motion tracking system will be utilized. Then two sensor fusion algorithms based on Kalman filter are formulated to estimate the joint angle of the limb from the reading of accelerometers and surface EMG. Initial results using tremor data from two Parkinson's disease patients show promising future in this sensor fusion. The sensing system and the algorithms proposed are useful for actively compensating the tremor and helping the clinicians in tremor diagnostics

Levodopa and the feedback process on set-shifting in Parkinson's disease

To study the interaction between levodopa and the feedback process on set-shifting in Parkinson's disease (PD). Methods: Functional magnetic resonance imaging (fMRI) studies were performed on 13 PD subjects and 17 age-matched healthy controls while they performed a modified card-sorting task. Experimental time periods were defined based on the types of feedback provided. PD subjects underwent the fMRI experiment twice, once during “off” medication (PDoff) and again after levodopa replacement (PDon). Results: Compared with normal subjects, the cognitive processing times were prolonged in PDoff but not in PDon subjects during learning through positive outcomes. The ability to set-shift through negative outcomes was not affected in PD subjects, even when “off” medication. Intergroup comparisons showed the lateral prefrontal cortex was deactivated in PDoff subjects during positive feedback learning, especially following internal feedback cues. The cortical activations were increased in the posterior brain regions in PDoff subjects following external feedback learning, especially when negative feedback cues were provided. Levodopa replacement did not completely restore the activation patterns in PD subjects to normal although activations in the corticostriatal loops were restored. Conclusion: PD subjects showed differential ability to set-shift, depending on the dopamine status as well as the types of feedback cues provided. PD subjects had difficulty performing set-shift tasks through positive outcomes when “off” medication, and showed improvement after levodopa replacement. The ability to set-shift through negative feedback was not affected in PD subjects even when “off” medication, possibly due to compensatory changes outside the nigrostriatal dopaminergic pathway

No association of DNM3 with age of onset in Asian Parkinson's disease

Background: Genetic variability in DNM3 have been shown to modify age of onset of Parkinson’s disease (PD) among LRRK2 Gly2019Ser carriers in North African Arab-Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other LRRK2 variants Gly2385Arg and Arg1628PPro increase PD risk. We aim to determine if the DNM3 locus is associated with age of PD onset in both carriers and non-carriers of LRRK2 risk variants in Asians. Methods: We analyzed the association of DNM3 rs2421947 genotypes with age of PD onset in 3,645 Chinese samples, of which 369 carry at least one of two Asian LRRK2 risk variants. Results: DNM3 rs2421947 genotypes were not associated with PD age of onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian LRRK2 risk variant carriers and non-carriers. Conclusions: DNM3 rs2421947 is not associated with age of PD onset in LRRK2 risk variant carriers and non-carriers in Chinese. Further studies in other Asian populations will be of interest.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)NMRC (Natl Medical Research Council, S’pore)Accepted versio