scholarly journals Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
R. Bhome ◽  
A. Zarkali ◽  
G. E. C. Thomas ◽  
J. E. Iglesias ◽  
J. H. Cole ◽  
...  

AbstractDepression is a common non-motor feature of Parkinson’s disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14–20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.

2021 ◽  
Author(s):  
Rohan Bhome ◽  
Angeliki Zarkali ◽  
James Cole ◽  
Rimona Weil

Objective Depression is a common non-motor feature of Parkinson's disease (PD) which confers significant morbidity and is often challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not yet been identified and may even represent potential therapeutic targets. Methods We performed structural and diffusion weighted imaging on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). We used fixel based analysis of diffusion weighted imaging data to calculate mean fibre cross section (FC) for white matter tracts connected to each subnucleus and assessed volume and FC at baseline and 14-20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each of the 50 thalamic subnuclei, adjusting for age, gender, intracranial volume and time. Results We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with decreases in white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. Conclusion We demonstrate that depression is associated with right thalamic PuA subnucleus volume loss and widespread thalamic white matter macrostructural changes, but that antidepressants may protect against volume loss in PD depression. Our work provides mechanistic insights for depression in PD, suggests possible benefits of actively treating depression, and a potential target for therapeutic intervention to the PuA subnucleus for PD depression.


2018 ◽  
Vol 126 (09) ◽  
pp. 546-552 ◽  
Author(s):  
Rolf Larisch ◽  
John Midgley ◽  
Johannes Dietrich ◽  
Rudolf Hoermann

Abstract Aim Patients on levothyroxine-treatment frequently have complaints although TSH is within the reference range. Moreover, FT3 is often low in these patients. The clinical significance of this disequilibrium is studied here. Patients, methods We conducted a retrospective longitudinal study including 319 patients with differentiated thyroid carcinoma on LT4-medication (1.8 [1.6,2.1] µg/kg body weight). Patients were followed at 2309 visits for at median 63 [46,81] months. Association of reported complaints during follow-up with changes in thyroid parameters were analysed using a generalised linear mixed model accounting for within-variability and intra-subject correlations. Results 26% of patients expressed hypothyroid and 9.7% hyperthyroid complaints at any one visit, rates per visit being 6.5% and 2%, respectively. During follow-up, median changes in spans were as follows, LT4-dose 0.49 [IQR 0.29,0.72] µg/kg, FT3 1.77 [1.25,2.32] pmol/l, FT4 9.80 [6.70,12.8] pmol/l and TSH 1.25 [0.42,2.36] mIU/l. While rates of both hypothyroid or hyperthyroid symptoms were significantly related to all three thyroid parameters, the relationship of hypothyroid symptoms with FT3 extended to a below reference TSH range. Hypothyroid symptom relief was associated with both a T4 dose giving TSH-suppression below the lower reference limit and FT3 elevated further into the upper half of its reference range. In multivariable analysis, relationships between complaints and FT3 concentrations remained significant after adjusting for gender, age and BMI. Conclusion Residual hypothyroid complaints in LT4-treated patients are specifically related to low FT3 concentrations. This supports an important role of FT3 for clinical decision making on dose adequacy, particularly in symptomatic athyreotic patients.


2020 ◽  
Vol 10 (4) ◽  
pp. 1643-1648 ◽  
Author(s):  
Wojciech Gryc ◽  
Kathryn A. Roberts ◽  
Cyrus P. Zabetian ◽  
Daniel Weintraub ◽  
John Q. Trojanowski ◽  
...  

Neuropsychiatric symptoms are common in Parkinson’s disease (PD). We investigated the relationship between neuropsychiatric symptoms and current and future diagnosis of PD dementia (PDD). Individuals with PD who had a study partner were enrolled (n = 696). Study partners were administered the Neuropsychiatric Inventory or Neuropsychiatric Inventory Questionnaire at baseline. Participants were assigned a cognitive diagnosis at baseline and follow up visits. Hallucinations were significantly associated with a diagnosis of PDD cross-sectionally (p < 0.001) and with shortened time to dementia longitudinally among initially nondemented participants (n = 444; p = 0.005). Screening for hallucinations may be useful for assessing risk of dementia in participants with PD.


2018 ◽  
Vol 8 (12) ◽  
pp. 2339 ◽  
Author(s):  
Zoltan Galaz ◽  
Jiri Mekyska ◽  
Vojtech Zvoncak ◽  
Jan Mucha ◽  
Tomas Kiska ◽  
...  

Hypokinetic dysarthria, which is associated with Parkinson’s disease (PD), affects several speech dimensions, including phonation. Although the scientific community has dealt with a quantitative analysis of phonation in PD patients, a complex research revealing probable relations between phonatory features and progress of PD is missing. Therefore, the aim of this study is to explore these relations and model them mathematically to be able to estimate progress of PD during a two-year follow-up. We enrolled 51 PD patients who were assessed by three commonly used clinical scales. In addition, we quantified eight possible phonatory disorders in five vowels. To identify the relationship between baseline phonatory features and changes in clinical scores, we performed a partial correlation analysis. Finally, we trained XGBoost models to predict the changes in clinical scores during a two-year follow-up. For two years, the patients’ voices became more aperiodic with increased microperturbations of frequency and amplitude. Next, the XGBoost models were able to predict changes in clinical scores with an error in range 11–26%. Although we identified some significant correlations between changes in phonatory features and clinical scores, they are less interpretable. This study suggests that it is possible to predict the progress of PD based on the acoustic analysis of phonation. Moreover, it recommends utilizing the sustained vowel /i/ instead of /a/.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Amir Pourmoghaddam ◽  
Marius Dettmer ◽  
Daniel P. O’Connor ◽  
William H. Paloski ◽  
Charles S. Layne

Analysis of electromyographic (EMG) data is a cornerstone of research related to motor control in Parkinson’s disease. Nonlinear EMG analysis tools have shown to be valuable, but analysis is often complex and interpretation of the data may be difficult. A previously introduced algorithm (SYNERGOS) that provides a single index value based on simultaneous multiple muscle activations (MMA) has been shown to be effective in detecting changes in EMG activation due to modifications of walking speeds in healthy adults. In this study, we investigated if SYNERGOS detects MMA changes associated with both different walking speeds and levodopa intake. Nine male Parkinsonian patients walked on a treadmill with increasing speed while on or off medication. We collected EMG data and computed SYNERGOS indices and employed a restricted maximum likelihood linear mixed model to the values. SYNERGOS was sensitive to neuromuscular modifications due to both alterations of gait speed and intake of levodopa. We believe that the current experiment provides evidence for the potential value of SYNERGOS as a nonlinear tool in clinical settings, by providing a single value index of MMA. This could help clinicians to evaluate the efficacy of interventions and treatments in Parkinson’s disease in a simple manner.


2017 ◽  
Author(s):  
Mahsa Dadar ◽  
Yashar Zeighami ◽  
Yvonne Yau ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Josefina Maranzano ◽  
...  

AbstractObjectiveWhite Matter Hyperintensities (WMHs) are associated with cognitive decline in normative aging and Alzheimer’s disease. However, the pathogenesis of cognitive decline in Parkinson’s disease (PD) is not directly related to vascular causes, and therefore the role of WMHs in PD remains unclear. If WMH has a higher impact on cognitive decline in PD, vascular pathology should be assessed and treated with a higher priority in this population. Here we investigate whether WMH leads to increased cognitive decline in PD, and if these effects relate to cortical thinningMethodsTo investigate the role of WMHs in PD, it is essential to study recently-diagnosed/non-treated patients.De novoPD patients and age-matched controls (NPD=365,NControl=174) with FLAIR/T2-weighted scans at baseline were selected from Parkinson’s Progression Markers Initiative (PPMI). WMHs and cortical thickness were measured to analyse the relationship between baseline WMHs and future cognitive decline (follow-up:4.09±1.14 years) and cortical thinning (follow-up:1.05±0.10 years).ResultsHigh WMH load (WMHL) at baseline in PD was associated with increased cognitive decline, significantly more than i) PDs with low WMHL and ii) controls with high WMHL. Furthermore, PD patients with higher baseline WMHL showed more cortical thinning in right frontal lobe than subjects with low WMHL. Cortical thinning of this region also predicted decline in performance on a cognitive test.InterpretationPresence of WMHs inde novoPD patients predicts greater future cognitive decline and cortical thinning than in normal aging. Recognizing WMHs as a potential predictor of cognitive deficit in PD provides an opportunity for timely interventions.


Neurosurgery ◽  
2005 ◽  
Vol 56 (2) ◽  
pp. 281-289 ◽  
Author(s):  
Mayumi Kitagawa ◽  
Jun-ichi Murata ◽  
Haruo Uesugi ◽  
Seiji Kikuchi ◽  
Hisatoshi Saito ◽  
...  

2019 ◽  
Author(s):  
Nadeesha Kalyani Hewa Haputhanthirige ◽  
Karen Sullivan ◽  
Gene Moyle ◽  
Sandy Brauer ◽  
Erica Rose Jeffrey ◽  
...  

Abstract Background Gait impairments in Parkinson’s disease (PD) limit independence and quality of life. While dance based interventions could improve gait, further studies are needed to determine if the benefits generalise to different terrains and when dual-tasking. The aim was to perform a feasibility study of the effects of a dance intervention, based on the Dance for PD®(DfPD®) program, on gait under different dual-tasks (verbal fluency, serial subtraction) and surfaces (even, uneven), and to determine if a larger scale follow-up RCT is warranted.Methods A dance group (DG; n = 17; age = 65.8 ± 11.7 years) and a control group (CG: n = 16; age = 67.0 ± 7.7 years) comprised of non-cognitively impaired (Addenbrooke’s score: DG = 93.2 ± 3.6, CG = 92.6 ± 4.3) independently locomoting people with PD (Hoehn & Yahr I-III) participated in the study. The DG undertook a one-hour DfPD®based class, twice weekly for 12 weeks. The CG had treatment as usual. Gait analysis was performed at baseline and post-intervention while walking on two surfaces (even, uneven) under three conditions (regular walking; dual-task: verbal-fluency, serial-subtraction). The data was analysed by means of a linear mixed model. ResultsThe DG improved significantly compared to the CG in gait velocity, cadence, step-length, and stride-length when even surface walking, with and without a dual-task. On the uneven surface the DG walked more cautiously during regular walking but had improved gait velocity, cadence and step-length when performing serial-subtractions. Conclusions DfPD®-based classes produced clinically significant improvement on spatiotemporal gait parameters under dual-task conditions and on uneven surfaces. This could arise from improved movement confidence and coordination; emotional expression; cognitive skills (planning, multitasking), and; utilisation of external movement cues. A large-scale RCT of this program is warranted.Trial registration A protocol for this study has been registered retrospectively at Australian New Zealand Clinical Trials Registry on 12.11.2018. Identifier: ACTRN12618001834246.


2021 ◽  
pp. jnnp-2021-326630
Author(s):  
Angeliki Zarkali ◽  
Peter McColgan ◽  
Louise Ann Leyland ◽  
Andrew John Lees ◽  
Rimona Sharon Weil

ObjectiveVisual hallucinations are common in Parkinson’s disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical in controlling cortical networks, structural thalamic changes could underlie network dysfunction in PD hallucinations.MethodsWe used whole-brain fixel-based analysis and cortical thickness measures to examine longitudinal white and grey matter changes in 76 patients with PD (15 hallucinators, 61 non-hallucinators) and 26 controls at baseline, and after 18 months. We compared white matter and cortical thickness, adjusting for age, gender, time-between-scans and intracranial volume. To assess thalamic changes, we extracted volumes for 50 thalamic subnuclei (25 each hemisphere) and mean fibre cross-section (FC) for white matter tracts originating in each subnucleus and examined longitudinal change in PD-hallucinators versus non-hallucinators.ResultsPD hallucinators showed white matter changes within the corpus callosum at baseline and extensive posterior tract involvement over time. Less extensive cortical thickness changes were only seen after follow-up. White matter connections from the right medial mediodorsal magnocellular thalamic nucleus showed reduced FC in PD hallucinators at baseline followed by volume reductions longitudinally. After follow-up, almost all thalamic subnuclei showed tract losses in PD hallucinators compared with non-hallucinators.InterpretationPD hallucinators show white matter loss particularly in posterior connections and in thalamic nuclei, over time with relatively preserved cortical thickness. The right medial mediodorsal thalamic nucleus shows both connectivity and volume loss in PD hallucinations. Our findings provide mechanistic insights into the drivers of network imbalance in PD hallucinations and potential therapeutic targets.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Stephanie A. Miller ◽  
Mindy Mayol ◽  
Elizabeth S. Moore ◽  
Audra Heron ◽  
Victoria Nicholos ◽  
...  

Background. Rates of progression of motor symptoms and physical performance show declines between 2% and 7% annually in community samples with Parkinson’s disease (PD). However, the effects of ongoing exercise behaviors on progression rates have not been considered. Objective. The primary purpose of this prospective, longitudinal study was to examine the annual rates of progression in activity and participation measures over five years in community-based exercisers with PD. Methods. A cohort of 55 regular exercisers with idiopathic PD was assessed at baseline and 1, 2, and 5 years. Regular exercise was defined as scores of 4-5 on the Stages for Readiness to Exercise Scale and a self-reported average of at least 60 minutes of exercise/week within six months of each testing session. Unadjusted and adjusted annual progression rates for activity and participation measures were calculated with a standardized equation of change from baseline. A linear mixed model with covariates of age at PD diagnosis and PD subtype was used to determine adjusted change scores. Results. Annual progression rates for unadjusted and adjusted variables were similar, and none exceeded 1.7% across time points for this group of exercisers with PD. Older age at PD diagnosis significantly contributed to faster progression of walking and balance functions. A nonlinear trajectory of the PD progression was demonstrated across most activity and participation outcomes. Conclusions. Annual progression rates demonstrated by this sample of exercisers were lower than those previously reported for motor decline in general samples with PD. Assessing activity and participation outcomes longitudinally at interim time points was important for understanding the trajectory of change over time. The lower rates of progression in this study warrant further investigation into the long-term effects of exercise in PD.


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