Longitudinal diffusion tensor imaging changes in early Parkinson’s disease: ICICLE-PD study

Minett, Thaís; Su, Li; Mak, Elijah; Williams, Guy B.; Firbank, Michael; Lawson, Rachael A.; Yarnall, Alison J.; Duncan, Gordon W.; Owen, Adrian M.; Khoo, Tien K.; Brooks, David J.; Rowe, James B.; Barker, Roger A.; Burn, David J.; O’Brien, John

doi:10.1007/s00415-018-8873-0

Cited by 42 publications

(44 citation statements)

References 50 publications

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“…Alterations in mean diffusivity in a cohort of PD patients with mild cognitive impairments compared with cognitively normal PD patients and a deterioration of WM could be used to infer longitudinal changes in cognitive outcomes, as recently reported. 27 Their results and ours reinforce the notion of different PD phenotypes having distinct patterns of WM degeneration.…”

Section: Discussionsupporting

confidence: 83%

White matter myelin profiles linked to clinical subtypes of Parkinson's disease

Baumeister

Kim

Zhu

et al. 2018

Magnetic Resonance Imaging

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Background White matter (WM) microstructural integrity is important for effective brain functioning and alterations have been shown in many neurodegenerative diseases. Purpose To investigate WM myelin profiles and their relation to clinical features of Parkinson's disease (PD). Study Type Retrospective cross‐sectional. Population In all, 29 PD subjects and 15 healthy controls. Field Strength/Sequence Multiecho GRASE with 10 msec echo spacing and echo planar imaging (EPI) diffusion‐weighted (b‐value = 700 with 32 gradient directions) on a 3T scanner. Assessment Myelin water fraction (MWF) and fractional anisotropy (FA) across 20 WM regions of interest (ROIs) were compared between groups. Partial least squares (PLS) was used to associate MWF and FA with clinical and behavioral measures. Statistical Tests Group comparisons were done using two‐sample t‐tests. PLS was assessed with permutation tests. Bootstrapping was used to investigate the robustness of imaging features. Results No group differences in myelin content could be detected with univariate tests. A three‐component PLS model linked MWF profiles to clinical phenotypes but no FA profiles. The three components appeared to follow along broad motor/nonmotor subtypes of “akinetic‐rigid,” “tremor‐predominant,” and “depression/apathy” subtypes, respectively. The first component showed associations between overall motor scores (r = –0.43, P = 0.0196) and cognitive performance (r = 0.44, P = 0.0171) with interhemispheric and long‐range association fibers. A second component linked overall motor scores (r = –0.58, P = 0.0009) and tremor scores (r = –0.48, P = 0.0091) to predominantly projection fibers. The last component related depression (r = –0.60, P = 0.0006) and apathy scores (r = –0.66, P = 0.0001 and r = –49, P = 0.0072) to a mixture of association and projection fibers. Data Conclusion MWF was robustly linked to distinct clinical subtypes of PD and may serve as an additional tool to characterize the disease. Level of Evidence: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:164–174.

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Section: Discussionsupporting

confidence: 83%

White matter myelin profiles linked to clinical subtypes of Parkinson's disease

Baumeister

Kim

Zhu

et al. 2018

Magnetic Resonance Imaging

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“…Intriguingly, the frontal areas involved match the distribution of impairment in striatal dopaminergic projections reported previously. A study in an independent patient group found a similar association between frontal WM integrity and cognition, corroborating the idea of early frontal microstructural involvement 52 .…”

Section: Findings To Datesupporting

confidence: 57%

Cohort Profile: the Oxford Parkinson’s Disease Centre Discovery Cohort Magnetic Resonance Imaging sub-study (OPDC-MRI)

Griffanti

Klein

Szewczyk-Królikowski

et al. 2019

Preprint

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Purpose: The Oxford Parkinson's Disease Centre (OPDC) Discovery Cohort magnetic resonance imaging (MRI) sub-study (OPDC-MRI) collects high quality multimodal brain MRI together with deep longitudinal clinical phenotyping in patients with Parkinson's, at-risk individuals and healthy elderly participants. The primary aim is to detect pathological changes in brain structure and function, and develop, together with the clinical data, biomarkers to stratify, predict and chart progression in early-stage Parkinson's and at-risk individuals. Participants: Participants are recruited from the OPDC Discovery Cohort, a prospective, longitudinal study. Baseline MRI data is currently available for 290 participants: 119 patients with early idiopathic Parkinson's, 15 Parkinson's patients with pathogenic mutations of the LRRK2 or GBA genes, 68 healthy controls and 87 individuals at risk of Parkinson's (asymptomatic carriers of GBA mutation and patients with idiopathic rapid eye movement sleep behaviour disorder - RBD). Findings to date: Differences in brain structure in early Parkinson's were found to be subtle, with small changes in the shape of the globus pallidus and evidence of alterations in microstructural integrity in the prefrontal cortex that correlated with performance on executive function tests. Brain function, as assayed with resting fMRI yielded more substantial differences, with basal ganglia connectivity reduced in early Parkinson's, and RBD, but not Alzheimer's, suggesting that the effect is pathology specific. Imaging of the substantia nigra with the more recent adoption of sequences sensitive to iron and neuromelanin content shows promising results in identifying early signs of Parkinsonian disease. Future plans: Ongoing studies include the integration of multimodal MRI measures to improve discrimination power. Follow-up clinical data are now accumulating and will allow us to correlate baseline imaging measures to clinical disease progression. Follow-up MRI scanning started in 2015 and is currently ongoing, providing the opportunity for future longitudinal imaging analyses with parallel clinical phenotyping.

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“…The cross-sectional results have been mixed with both ROI analysis and TBSS, with some studies showing no correlations between DTI-derived metrics and clinical measures (38,48) and other studies reporting significant correlations, particularly in the caudate nucleus (34,41). Minett et al (51) found that at baseline patients with early-stage PD had significantly higher MD relative to HC, and in patients with PD and mild cognitive impairment, higher MD was significantly correlated with lower attention and executive function scores. In this longitudinal study, DTIderived WM microstructural changes were assessed as potential prognostic biomarkers of worsening motor features or cognitive decline in patients with PD.…”

Section: Dti In Early-stage Pdmentioning

confidence: 99%

Assessing White Matter Pathology in Early-Stage Parkinson Disease Using Diffusion MRI: A Systematic Review

et al. 2020

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Longitudinal diffusion tensor imaging changes in early Parkinson’s disease: ICICLE-PD study

Abstract: Mean diffusivity represents an important correlate of cognitive function and predictor of motor impairment in Parkinson's disease: DTI is potentially a useful tool in stratification of patients into clinical trials and to monitor the impact of treatment on motor function.

Cited by 42 publications

References 50 publications

White matter myelin profiles linked to clinical subtypes of Parkinson's disease

White matter myelin profiles linked to clinical subtypes of Parkinson's disease

Cohort Profile: the Oxford Parkinson’s Disease Centre Discovery Cohort Magnetic Resonance Imaging sub-study (OPDC-MRI)

Assessing White Matter Pathology in Early-Stage Parkinson Disease Using Diffusion MRI: A Systematic Review

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