Cognitive decline in Parkinson's disease (PD) is a highly prevalent condition with no effective treatment. Cortical atrophy is thought to promote its development but to design optimal therapeutic ...approaches in this clinical setting we need to understand the physiopathological mechanisms leading to this disorder.
To characterize the impact of dopaminergic degeneration on cortical integrity in early PD.
We studied 87 recently-diagnosed PD patients and 38 healthy controls from the Parkinson's Progression Marker Initiative who underwent I123-ioflupane SPECT (DATSCAN) and T1-MRI imaging. Using Freesurfer 6.0, we characterized baseline and longitudinal (one-year) correlations between striatal DAT uptake and cortical thickness. We also addressed the association between these imaging biomarkers and cognitive measures.
Reduced DAT uptake in PD patients was associated with cross-sectional and longitudinal cortical thinning in frontal and posterior-cortical brain regions. Imaging parameters correlated with cognitive indicators in multiple domains that extend beyond frontal-executive tasks. Dopaminergic medication attenuated the longitudinal loss of cortical integrity in frontal and a subset of parietal regions, but not in other key regions such as the precuneus.
To date, posterior cortical alterations in PD, known to play a major role in the development of PD-dementia, have mainly been attributed to a cholinergic degeneration occurring in later stages of the disease. Our results suggest that dopamine loss also promotes posterior-cortical atrophy from the very early stages of Parkinson's disease, which may have potential clinical and therapeutic implications.
•Dementia in Parkinson's disease is a prevalent condition with no effective treatment.•We need to understand the processes leading to cortical damage in this disease.•We characterize the relationship between dopamine loss and cortical deterioration.•Dopamine loss induces frontal and posterior-cortical thinning in early disease stages.
Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. ...However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of cognitive impairment. In this work, we intended to assess functional connectivity and graph theoretical measures and their relation to gray matter loss in Parkinson's disease with mild cognitive impairment (PD‐MCI). We recruited 53 Parkinson's disease patients and classified them for cognitive impairment using Level‐1 Movement Disorders Society‐Task Force Criteria. Voxel‐based morphometry, functional connectivity and graph theoretical measures were obtained on a 3‐Tesla MRI scanner. Loss of gray matter was observed in the default mode network (bilateral precuneus), without a corresponding disruption of functional or graph theoretical properties. However, functional and graph theoretical changes appeared in salience network nodes, without evidence of gray matter loss. Global cognition and executive scores showed a correlation with node degree in the right anterior insula. We also found a correlation between visuospatial scores and right supramarginal gyrus node degree. Our findings highlight the loss of functional connectivity and topological features without structural damage in salience network regions in PD‐MCI. They also underline the importance of multimodal hubs in the transition to mild cognitive impairment. This functional disruption in the absence of gray matter atrophy suggests that the salience network is a key vulnerable system at the onset of mild cognitive impairment in PD.
Objective
To determine the cutoffs that optimized the agreement between 18F‐Florbetapir positron emission tomography (PET) and Aβ1‐42, Aβ1‐40, tTau, pTau and their ratios measured in cerebrospinal ...fluid (CSF) on the LUMIPULSE G600II instrument, we quantified the levels of these four biomarkers in 94 CSF samples from participants of the Sant Pau Initiative on Neurodegeneration (SPIN cohort) using the Lumipulse G System with available 18F‐Florbetapir imaging.
Methods
Participants had mild cognitive impairment (n = 35), AD dementia (n = 12), other dementias or neurodegenerative diseases (n = 41), or were cognitively normal controls (n = 6). Levels of Aβ1‐42 were standardized to certified reference material. Amyloid scans were assessed visually and through automated quantification. We determined the cutoffs of CSF biomarkers that optimized their agreement with 18F‐Florbetapir PET and evaluated concordance between markers of the amyloid category.
Results
Aβ1‐42, tTau and pTau (but not Aβ1‐40) and the ratios with Aβ1‐42 had good diagnostic agreement with 18F‐Florbetapir PET. As a marker of amyloid pathology, the Aβ1‐42/Aβ1‐40 ratio had higher agreement and better correlation with amyloid PET than Aβ1‐42 alone.
Interpretation
CSF biomarkers measured with the Lumipulse G System show good agreement with amyloid imaging in a clinical setting with heterogeneous presentations of neurological disorders. Combination of Aβ1‐42 with Aβ1‐40 increases the agreement between markers of amyloid pathology.
Background
Although several progressive supranuclear palsy (PSP) phenotypes have recently been described, studies identifying cognitive and neuropsychiatric differences between them are lacking.
...Methods
An extensive battery of cognitive and behavioural assessments was administered to 63 PSP patients, 25 PD patients with similar sociodemographic characteristics, and 25 healthy controls. We analysed differences in phenomenology, frequency and severity of cognitive and neuropsychiatric symptoms between PSP, PD and HC, and between PSP subtypes.
Results
Regarding phenotypes, 64.6% met criteria for Richardson’s syndrome (PSP-RS), 10.7% PSP with predominant Parkinsonism (PSP-P), 10.7% with PSP progressive gait freezing (PSP-PGF), and 10.7% PSP with predominant speech/language disorder (PSP-SL). Impairment was more severe in the PSP group than in the PD and HC groups regarding motor scores, cognitive testing and neuropsychiatric scales. Cognitive testing did not clearly differentiate between PSP phenotypes, but PSP-RS and PSP-SL appeared to have more cognitive impairment than PSP-PGF and PSP-P, mainly due to an increased impairment in frontal executive domains. Regarding neuropsychiatric disturbances, no specific behavior was more common in any of the PSP subtypes.
Conclusion
Motor deficits delineate the phenotypes included in currently accepted MDS-PSP criteria. Cognition and behavioural disturbances are common in PSP and allow us to distinguish this disorder from other neurological diseases, but they do not differentiate between PSP phenotypes.
In Huntington’s disease (HD), irritability and aggressive behavior represent highly prevalent and disabling neuropsychiatric symptoms. However, their structural brain correlates have not been ...extensively explored. Here, we rated the severity of irritability and aggression (IAs) using the Problem Behaviors Assessment for HD (PBA-s) in 31 early HD participants. The IAs score was computed as the mean severity score for the irritability plus the mean severity aggression PBA-s items. Seventeen patients were classified as IAs (IAs score > 2) and 14 as non-IAs. All participants had available T1-MRI data. A grey matter volume voxel-based morphometry group comparison was performed, using age, motor status, severity of other PBA-s items and disease burden as covariates. Aside from irritability, aggression and obsessive-compulsive behavior, both groups were comparable in terms of other clinical and sociodemographic variables. In the IAs group, a significant reduction of grey-matter volume (GMV) was found in the bilateral caudate, putamen and globus pallidus, left pulvinar nucleus, right superior temporal pole (BA 38), left mid temporal gyrus (BA 21), right inferior temporal gyrus (BA 20) and left medial OPFC (BA 11). Lower GMV in the left pulvinar nucleus was significantly associated with higher anxiety and lower GMV in the left medial OPFC was significantly associated with higher suicidality. In sum, IAs in HD is associated with structural brain damage in a set of key nodes involved in the expression and down-regulation of negative emotions.
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