Visual exploration in Parkinson's disease and Parkinson's disease dementia

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual searc

A water budget dichotomy of rocky protoplanets from 26^{26}Al-heating

In contrast to the water-poor inner solar system planets, stochasticity during planetary formation and order of magnitude deviations in exoplanet volatile contents suggest that rocky worlds engulfed in thick volatile ice layers are the dominant family of terrestrial analogues among the extrasolar planet population. However, the distribution of compositionally Earth-like planets remains insufficiently constrained, and it is not clear whether the solar system is a statistical outlier or can be explained by more general planetary formation processes. Here we employ numerical models of planet formation, evolution, and interior structure, to show that a planet's bulk water fraction and radius are anti-correlated with initial $^{26}$Al levels in the planetesimal-based accretion framework. The heat generated by this short-lived radionuclide rapidly dehydrates planetesimals prior to accretion onto larger protoplanets and yields a system-wide correlation of planet bulk abundances, which, for instance, can explain the lack of a clear orbital trend in the water budgets of the TRAPPIST-1 planets. Qualitatively, our models suggest two main scenarios of planetary systems' formation: high-$^{26}$Al systems, like our solar system, form small, water-depleted planets, whereas those devoid of $^{26}$Al predominantly form ocean worlds, where the mean planet radii between both scenarios deviate by up to about 10%.Comment: Preprint version; free-to-read journal version at https://rdcu.be/bmdlw; blog article at https://t.co/p6SValG1i

Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases

Objective: To examine the utility of the new Movement Disorder Society (MDS) diagnostic criteria in a large cohort of Parkinson's disease (PD) patients. Methods: Recently diagnosed (&lt;3.5 years) PD cases fulfilling United Kingdom (UK) brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural history study were assessed by retrospective application of the MDS criteria. Results: In 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving 165 (8.3%) not fulfilling criteria. Clinically established cases were significantly more likely to have limb rest tremor (89.3%), a good l-dopa response (79.5%), and olfactory loss (71.1%), than clinically probable cases (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and ‘not PD’ cases were less evident. In cases not fulfilling criteria, the mean MDS UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3, SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher than in probable PD (250 mg, SD 214, p &lt; 0.001) and established PD (308 mg, SD 199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established cases at baseline remained as PD (established/probable), and 86.9% of those categorized as clinically probable at baseline remained as PD (established/probable). Cases not fulfilling PD criteria had more severe parkinsonism, in particular relating to postural instability, gait problems, and cognitive impairment. Conclusion: Over 90% of cases clinically diagnosed as early PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an atypical parkinsonian disorder or secondary parkinsonism that is not correctly identified by the UK Brain Bank criteria, but possibly by the new criteria

Landscape Transformation During Ceramic Age and Colonial Occupations of Barbuda, West Indies

This research documented the history of landscape transformation on the island of Barbuda in the Lesser Antilles, Caribbean through cross-disciplinary research approaches. Excavations confirmed a human presence for the seasonal exploitation of conch meat and other mollusks during the Archaic Age (c.3000–500 BC), but more substantial impacts to terrestrial ecosystems likely began during the Ceramic Age (c.500 BC–AD 1500). Our combined sedimentary and charcoal records revealed that human-induced environmental transformations began with Ceramic Age peoples as they cleared vegetation for settlements and gardens with intentional burning. Sedimentary charcoal indicated a dramatic decline in fire during post-Ceramic Age abandonment, continuing through the Colonial Period, as the dominant human activities shifted to herding, farming, and selective wood harvesting. Historical sources showed that during the Colonial Period (post-1492), the island was intermittently settled until the mid-seventeenth century, while the Codrington family of Antigua held the lease to the island from 1681 to 1870. They used the island for farming and stock-rearing, exporting meat and draught animals along with lime, timber, and subsistence crops. Macrocharcoal recovered from Colonial Period archaeological sites reflect the use of a variety of local species and wood imported to the island or harvested from shipwrecks

Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease

Funded by Parkinson's UK National Institute for Health Research (NIHR) DeNDRoN network NIHR Newcastle Biomedical Research Unit Newcastle University NIHR funded Biomedical Research Centre in CambridgePeer reviewedPublisher PD

Conjugated dendrimers: A modular approach to materials for full colour displays

Conjugated dendrimers provide an excellent molecular architecture for tuning material properties for organic light emitting diodes. Here we demonstrate a modular approach allowing highly efficient fluorescent and phosphorescent emissive chromophores to be used to make red, green and blue solution-processed light emitting diodes. The choice of a common dendritic architecture ensures good solubility and film forming properties irrespective of the choice of core unit. In addition, this architecture allows blending of dendrimers with different cores without phase separation. We show that blending provides a simple but powerful way of tuning the colour of dendrimer LEDs from deep blue to blue-green, and from green to red with little impact on the device properties

Predicting cognitive decline using neuropsychiatric symptoms in prodromal Lewy body dementia: A longitudinal study

Introduction: Neuropsychiatric symptoms (NPS) in Lewy body dementias (LBD) occur frequently and early in disease progression. Such symptoms are associated with worse quality of life, caregiver burden and functional limitations. Limited evidence exists, however, outlining the longitudinal relationship between NPS and cognitive decline in prodromal LBD. Methods: 123 participants were derived from three cohort studies. Patients with mild cognitive impairment (MCI) relating to probable dementia with Lewy bodies (MCI-LB, n = 67) and Parkinson's disease (PD-MCI, n = 56) completed comprehensive cognitive and neuropsychiatric assessment and were followed up longitudinally. Linear regression and mixed effects models assessed the relationship between baseline NPS and cognition at baseline and over time. Results: In MCI-LB, overall NPS burden was associated with declines over time in executive function (p = 0.026) and processing speed (p = 0.028) and baseline aberrant motor behaviour was associated with declines in attention (p < 0.025). Anxiety was significantly associated with poorer visuospatial functioning (p = 0.016) at baseline and poorer attention both at baseline (p = 0.017) and across time points (p = 0.024). In PD-MCI, psychosis was associated with poorer executive functioning at baseline (p = 0.008) and across time points (p = 0.002) but had no association with changes longitudinally. Conclusions: Core neuropsychiatric components of LBD are not strongly associated with cognition in prodromal disease. This may suggest that neuropathological mechanisms underlying NPS may not be the same as those underlying cognitive impairment. Non-core NPS, however, may be more directly associated with cognitive change. Future studies utilising neuroimaging techniques are needed to explore the neuropathological basis of NPS in prodromal LBD

Baseline and longitudinal grey matter changes in newly diagnosed Parkinson\u27s disease: ICICLE-PD study

Mild cognitive impairment in Parkinson\u27s disease is associated with progression to dementia (Parkinson\u27s disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson\u27s disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects with newly diagnosed idiopathic Parkinson\u27s disease and 37 healthy matched controls had serial 3 T structural magnetic resonance imaging scans with clinical and neuropsychological assessments at baseline, which were repeated after 18 months. The Movement Disorder Society Task Force criteria were used to classify the Parkinson\u27s disease subjects into Parkinson\u27s disease with mild cognitive impairment (n = 39) and Parkinson\u27s disease with no cognitive impairment (n = 66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. At baseline, cases with Parkinson\u27s disease with mild cognitive impairment demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and subjects with Parkinson\u27s disease with no cognitive impairment. Regional cortical thickness at baseline was correlated with global cognition in the combined Parkinson\u27s disease cohort. Over 18 months, patients with Parkinson\u27s disease with mild cognitive impairment demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to those with Parkinson\u27s disease and no cognitive impairment and healthy controls, whereas subjects with Parkinson\u27s disease and no cognitive impairment showed more severe frontal cortical thinning compared to healthy controls. At baseline, Parkinson\u27s disease with no cognitive impairment converters showed bilateral temporal cortex thinning relative to the Parkinson\u27s disease with no cognitive impairment stable subjects. Although loss of both cortical and subcortical volume occurs in non-demented Parkinson\u27s disease, our longitudinal analyses revealed that Parkinson\u27s disease with mild cognitive impairment shows more extensive atrophy and greater percentage of cortical thinning compared to Parkinson\u27s disease with no cognitive impairment. In particular, an extension of cortical thinning in the temporo-parietal regions in addition to frontal atrophy could be a biomarker in therapeutic studies of mild cognitive impairment in Parkinson\u27s disease for progression towards dementia

Characterisation of the bacterial and fungal communities associated with different lesion sizes of Dark Spot Syndrome occurring in the Coral Stephanocoenia intersepta

The number and prevalence of coral diseases/syndromes are increasing worldwide. Dark Spot Syndrome (DSS) afflicts numerous coral species and is widespread throughout the Caribbean, yet there are no known causal agents. In this study we aimed to characterise the microbial communities (bacteria and fungi) associated with DSS lesions affecting the coral Stephanocoenia intersepta using nonculture molecular techniques. Bacterial diversity of healthy tissues (H), those in advance of the lesion interface (apparently healthy AH), and three sizes of disease lesions (small, medium, and large) varied significantly (ANOSIM R = 0.052 p,0.001), apart from the medium and large lesions, which were similar in their community profile. Four bacteria fitted into the pattern expected from potential pathogens; namely absent from H, increasing in abundance within AH, and dominant in the lesions themselves. These included ribotypes related to Corynebacterium (KC190237), Acinetobacter (KC190251), Parvularculaceae (KC19027), and Oscillatoria (KC190271). Furthermore, two Vibrio species, a genus including many proposed coral pathogens, dominated the disease lesion and were absent from H and AH tissues, making them candidates as potential pathogens for DSS. In contrast, other members of bacteria from the same genus, such as V. harveyii were present throughout all sample types, supporting previous studies where potential coral pathogens exist in healthy tissues. Fungal diversity varied significantly as well, however the main difference between diseased and healthy tissues was the dominance of one ribotype, closely related to the plant pathogen, Rhytisma acerinum, a known causal agent of tar spot on tree leaves. As the corals’ symbiotic algae have been shown to turn to a darker pigmented state in DSS (giving rise to the syndromes name), the two most likely pathogens are R. acerinum and the bacterium Oscillatoria, which has been identified as the causal agent of the colouration in Black Band Disease, another widespread coral disease

L-dopa responsiveness in early Parkinson's disease is associated with the rate of motor progression.

BACKGROUND: L-dopa responsiveness in Parkinson's disease (PD) varies, but the clinical correlates and significance of this are ill-defined. METHODS: Patients were assessed before and after their usual morning L-dopa dose, using the MDS Unified PD Rating Scale Part 3 (MDS UPDRS 3), and rated as definite responders (≥24.5% improvement) or limited responders (<24.5%). RESULTS: 1007 cases, mean age 66.1 years (SD 9.1) at diagnosis, were assessed 3.4 (SD 0.9) years after diagnosis. The L-dopa response was definite in 614 cases (61.0%), median reduction in MDS UPDRS 3 scores was 42.0%, (IQR 33.3, 53.1), and was limited in 393 cases (39.0%), median reduction in MDS UPDRS 3 scores 11.5% (IQR 4.3, 18.2). Definite responders were younger (66.3 years at study entry, SD 9.3) than limited responders (69.2 years, SD 8.4, p < 0.001). The MDS UPDRS 3 score at study entry in definite responders (21.0, SD 10.5) was significantly lower than in limited responders (24.7, SD 13.4, p < 0.001). The MDS UPDRS 3 increase over 18 months was less in definite responders at 3.0 (SD 10.4), compared to limited responders (6.4, SD 11.0, p < 0.001). The levodopa equivalent daily dose (LEDD) was not significantly different at study entry (definite responders 317 mg, SD 199, vs limited responders 305 mg, SD 191, p = 0.53). However, LEDD was significantly higher at the time of the L-dopa challenge test in definite responders (541 mg, SD 293) compared to limited responders (485 mg, SD 215, p = 0.01). Responsiveness to L-dopa was unaffected by the challenge test dose (p = 0.54). CONCLUSIONS: The main determinants of variation in the L-dopa response in early PD are age and motor severity. A limited L-dopa response is associated with faster motor progression