Cortical thinning correlates of changes in visuospatial and visuoperceptual performance in Parkinson's disease: A 4-year follow-up

Background. Growing evidence highlights the relevance of posterior cortically-based cognitive deficits in Parkinson's disease (PD) as possible biomarkers of the evolution to dementia. Cross-sectional correlational studies have established a relationship between the degree of atrophy in posterior brain regions and visuospatial and visuoperceptual (VS/VP) impairment. The aim of this study is to address the progressive cortical thinning correlates of VS/VP performance in PD. Methods. Forty-four PD patients and 20 matched healthy subjects were included in this study and followed for 4 years. Tests used to assess VS/VP functions included were: Benton's Judgement of Line Orientation (JLOT), Facial Recognition (FRT), and Visual Form Discrimination (VFDT) Tests; Symbol Digit Modalities Test (SDMT); and the Pentagon Copying Test (PCT). Structural magnetic resonance imaging data and FreeSurfer were used to evaluate cortical thinning evolution. Results. PD patients with normal cognition (PD-NC) and PD patients with mild cognitive impairment (PD-MCI) differed significantly in the progression of cortical thinning in posterior regions. In PD-MCI patients, the change in VS/VP functions assessed by PCT, JLOT, FRT, and SMDT correlated with the symmetrized percent change of cortical thinning of occipital, parietal, and temporal regions. In PD-NC patients, we also observed a correlation between changes in FRT and thinning in parieto-occipital regions. Conclusion. In this study, we establish the neuroanatomical substrate of progressive changes in VS/VP performance in PD patients with and without MCI. In agreement with cross-sectional data, VS/VP changes over time are related to cortical thinning in posterior regions

Structural and functional magnetic resonance imaging in isolated REM sleep behavior disorder: A systematic review of studies using neuroimaging software.

Isolated rapid eye movement sleep behavior disorder (iRBD) is a harbinger for developing clinical synucleinopathies. Magnetic resonance imaging (MRI) has been suggested as a tool for understanding the brain bases of iRBD and its evolution. This review systematically analyzed original full text articles on structural and functional MRI in patients with video-polysomnography-confirmed iRBD according to systematic procedures suggested by Reviews and Meta-analyses (PRISMA). The literature search was conducted via the PubMed database for articles related to structural and functional MRI in iRBD from 2000 to 2020. Investigations to date have been diverse in terms of methodology, but most agree that patients with iRBD have structural changes in deep gray matter nuclei, cortical gray matter atrophy, and disrupted functional connectivity within the basal ganglia, the cortico-striatal and cortico-cortical networks. Furthermore, there is evidence that MRI detects structural and functional brain changes associated with the motor and non-motor symptoms of iRBD. The current review highlights the need for larger multicenter and longitudinal studies, using complex approaches based on data-driven and unsupervised machine learning that will help to identify structural and functional patterns of brain degeneration. In turn, this may even allow for the prediction of subsequent phenoconversion from iRBD to the clinically defined synucleinopathie

Oculo-visual dysfunction in Parkinson's disease

This review describes the oculo-visual problems likely to be encountered in Parkinson's disease (PD) with special reference to three questions: (1) are there visual symptoms characteristic of the prodromal phase of PD, (2) is PD dementia associated with specific visual changes, and (3) can visual symptoms help in the differential diagnosis of the parkinsonian syndromes, viz. PD, progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD)? Oculo-visual dysfunction in PD can involve visual acuity, dynamic contrast sensitivity, colour discrimination, pupil reactivity, eye movement, motion perception, and visual processing speeds. In addition, disturbance of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations may be present. Prodromal features of PD may include autonomic system dysfunction potentially affecting pupil reactivity, abnormal colour vision, abnormal stereopsis associated with postural instability, defects in smooth pursuit eye movements, and deficits in visuo-motor adaptation, especially when accompanied by idiopathic rapid eye movement (REM) sleep behaviour disorder. PD dementia is associated with the exacerbation of many oculo-visual problems but those involving eye movements, visuo-spatial function, and visual hallucinations are most characteristic. Useful diagnostic features in differentiating the parkinsonian symptoms are the presence of visual hallucinations, visuo-spatial problems, and variation in saccadic eye movement dysfunction

Progression of Parkinson's disease patients' subtypes based on cortical thinning: 4-year follow-up

Background. Three cortical atrophy patterns were previously identified in non-demented Parkinson's disease patients using a data-driven approach based on cortical thickness data: i) parieto-temporal pattern of atrophy with worse cognitive performance (pattern 1), ii) occipital and frontal cortical atrophy with younger disease onset (pattern 2), and iii) non-detectable cortical atrophy (pattern 3). We aimed to investigate the evolution of these three patterns over time. Methods. Magnetic resonance imaging and neuropsychological assessment were obtained at baseline and follow-up (3.8±0.4 year apart) in a group of 45 Parkinson's disease patients and 22 healthy controls. FreeSurfer was used for cortical thickness analysis and global atrophy measures. Results. Temporo-parietal cortical thinning occurred in pattern 2, 3 and controls groups, and patients showed decline in processing speed (as measured by the Stroop Word-Color test, the Symbol Digits Modalities test and the Trail Making Test Part B) and in semantic fluency (animals). Pattern 3 patients showed more progressive cortical thinning in the left prefrontal cortex than controls and more right occipital thinning than pattern 2 patients over time. Pattern 1 patients had greater compromise in activities of the daily living and suffered higher attrition rate. Conclusion. The Parkinson's disease phenotypes identified using cluster analysis of cortical thickness data showed different progression over time. The presence of prefrontal thinning and younger disease onset at baseline was associated to less cortical degeneration, while non-atrophic patients progressed showing a temporo-parietal cortical thinning

The impact of dopaminergic treatment over cognitive networks in Parkinson's disease: Stemming the tide?

Dopamine-replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting-state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity-as in other networks- and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age-matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow-up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default-mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN-DMN connectivity characterized the participants in the ON state, while within-DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN-DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN-DM hyperconnectivity

Neuroimaging biomarkers associated with clinical dysfunction in Parkinson disease

Parkinson disease (PD) is the second most common neurodegenerative disorder in the world, directly affecting 2-3% of the population over the age of 65. People diagnosed with the disorder can experience motor, autonomic, cognitive, sensory and neuropsychiatric symptoms that can significantly impact quality of life. Uncertainty still exists about the pathophysiological mechanisms that underlie a range of clinical features of the disorder, linked to structural as well as functional brain changes. This thesis thus aimed to uncover neuroimaging biomarkers associated with clinical dysfunction in PD. A 'hubs-and-spokes' neural circuit-based approach can contribute to this aim, by analysing the component elements and also the interconnections of important brain networks. This thesis focusses on structures within basal ganglia-thalamocortical neuronal circuits that are linked to a range functions impacted in the disorder, and that are vulnerable to the consequences of PD pathology. This thesis investigated neuronal 'hubs' by studying the morphology of the caudate nucleus, putamen, thalamus and neocortex. The caudate nucleus, putamen and thalamus are all vital subcortical 'hubs' that play important roles in a number of functional domains that are compromised in PD. The neocortex, on the other hand, has a range of 'hubs' spread across it, regions of the brain that are crucial for neuronal signalling and communication. The interconnections, or 'spokes', between these hubs and other brain regions were investigated using seed-based resting-state functional connectivity analyses. Finally, a morphological analysis was used to investigate possible structural changes to the corpus callosum, the major inter-hemispheric white matter tract of the brain, crucial to effective higher-order brain processes. This thesis demonstrates that the caudate nucleus, putamen, thalamus, corpus callosum and neocortex are all atrophied in PD participants with dementia. PD participants also demonstrated a significant correlation between volumes of the caudate nuclei and general cognitive functioning and speed, while putamina volumes were correlated with general motor function. Cognitively unimpaired PD participants demonstrated minimal morphological alterations compared to control participants, however they demonstrated significant increases in functional connectivity of the caudate nucleus, putamen and thalamus with areas across the frontal lobe, and decreases in functional connectivity with parietal and cerebellar regions. PD participants with mild cognitive impairment and dementia show decreased functional connectivity of the thalamus with paracingulate and posterior cingulate cortices, respectively. This thesis contributes a deeper understanding of the relationship between structures of basal ganglia-thalamocortical neuronal circuits, corpus callosal and neocortical morphology, and the clinical dysfunction associated with PD. This thesis suggests that functional connectivity changes are more common in early stages of the disorder, while morphological alterations are more pronounced in advanced disease stages

The impact of dopaminergic treatment over cognitive networks in Parkinson's disease : Stemming the tide?

Altres ajuts: Fundació la Marató de TV3/20142910Dopamine-replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting-state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity-as in other networks- and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age-matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow-up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default-mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN-DMN connectivity characterized the participants in the ON state, while within-DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN-DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN-DM hyperconnectivity

Mild Cognitive Impairment in Parkinson's Disease - What Is It?

PURPOSE OF REVIEW: Mild cognitive impairment is a common feature of Parkinson’s disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson’s disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson’s disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson’s disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson’s disease. RECENT FINDINGS: Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson’s disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson’s provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. SUMMARY: Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson’s disease

Structural brain correlates of dementia in Huntington's disease

Altres ajuts: The present study was partially funded by the "Human Biology Project Grant" of the Huntington's Disease Society of America (USA).Huntington's disease (HD) is a fatal genetic neurodegenerative disorder with no effective treatment currently available. Progressive basal ganglia and whole-brain atrophy and concurrent cognitive deterioration are prototypical aspects of HD. However, the specific patterns of brain atrophy underlying cognitive impairment of different severity in HD are poorly understood. The aim of this study was to investigate the specific structural brain correlates of major cognitive deficits in HD and to explore its association with neuropsychological indicators. Thirty-five symptomatic early-to-mild HD patients and 15 healthy controls (HC) with available T1-MRI imaging were included in this study. In this cross-sectional study, HD patients were classified as patients with (HD-Dem) and without (HD-ND) major cognitive impairment in the range of dementia. This classification was based on previously validated PD-CRS cutoff scores for HD. Differences in brain atrophy across groups were studied by means of grey-matter volume voxel-based morphometry (GMV-VBM) and cortical thickness (Cth). Voxelwise and vertexwise general linear models were used to assess the group comparisons, controlling for the effects of age, sex, education, CAG repeat length and severity of motor symptoms. Clusters surviving p < 0.05 and family-wise error (FWE) correction were considered statistically significant. In order to characterize the impact on cognitive performance of the observed brain differences across groups, GMV and Cth values in the set of significant regions were computed and correlated with specific neuropsychological tests. All groups had similar sociodemographic profiles, and the HD groups did not significantly differ in terms of CAG repeat length. Compared to HC, both HD groups exhibited significant atrophy in multiple subcortical and parietal brain regions. However, compared to HC and HD-ND groups, HD-Dem patients showed a more prominent pattern of reduced GMV and cortical thinning. Importantly, this thinning was restricted to regions of the parietal-temporal and occipital cortices. Furthermore, these brain alterations were further associated with poorer cognitive performance in tasks assessing frontal-executive and attention domains as well as memory, language and constructional abilities. Major cognitive impairment in the range of dementia in HD is associated with brain and cognitive alterations exceeding the prototypical frontal-executive deficits commonly recognized in HD. The observed posterior-cortical damage identified by MRI and its association with memory, language, and visuoconstructive dysfunction suggest a strong involvement of extra-striatal atrophy in the onset of severe cognitive dysfunction in HD patients. Critically, major cognitive impairment in this sample was not associated with CAG repeat length, age or education. This finding could support a possible involvement of additional neuropathological mechanisms aggravating cognitive deterioration in HD

Ocular manifestations of Parkinson disease

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. We aimed to review both the disease and the drug-related ocular manifestations of PD. Methods: In this manuscript, we have reviewed and summarized existing literature on the ocular manifestations and drug-related complications of PD. We have also discussed the use of current noninvasive imaging techniques, such as optical coherence tomography (OCT), for the early diagnosis and monitoring of PD. Results: Impaired color vision, reduced stereopsis, reduced contrast sensitivity, pupillary abnormalities, eye movement disorders, convergence insufficiency, dry eye syndrome, glaucoma, visual dysfunctions, retinal abnormalities, and drug-related side effects were among the listed ocular manifestations of PD. There is a large knowledge gap regarding the type of glaucoma affecting PD patients—whether it is open-angle or other types. Further case studies and long-term follow-ups during PD progression are necessary to fill this gap. Patient compliance with follow-up visits for more visual field tests and OCT during PD progression may become problematic when dementia and cognitive impairment occur. Conclusions: There is a general need for clinicians to perform further tests and more visual examinations to rule out ocular manifestations. Furthermore, additional clinical trials are needed to further evaluate the use of different types of OCT findings as biomarkers of PD progression. This would aid in early diagnosis and in delaying disease progression, if treated promptly