Summary Normal maintenance of human motivation depends on the integrity of subcortical structures that link the prefrontal cortex with the limbic system. Structural and functional disruption of ...different networks within these circuits alters the maintenance of spontaneous mental activity and the capacity of affected individuals to associate emotions with complex stimuli. The clinical manifestations of these changes include a continuum of abnormalities in goal-oriented behaviours known as apathy. Apathy is highly prevalent in Parkinson's disease (and across many neurodegenerative disorders) and can severely affect the quality of life of both patients and caregivers. Differentiation of apathy from depression, and discrimination of its cognitive, emotional, and auto-activation components could guide an individualised approach to the treatment of symptoms. The opportunity to manipulate dopaminergic treatment in Parkinson's disease allows researchers to study a continuous range of motivational states, from apathy to impulse control disorders. Parkinson's disease can thus be viewed as a model that provides insight into the neural substrates of apathy.
Abstract Relatively subtle cognitive disturbances may be present from the initial stages of Parkinson's disease (PD) that progress in many patients to a more severe cognitive impairment and dementia. ...Several of the initial deficits are ascribed to failure in the frontal–striatal basal ganglia circuits and involve executive defects in planning, initiation, monitoring of goal-directed behaviors and working-memory. Other non-demented PD patients also exhibit visuospatial and memory deficits more representative of posterior cortical functioning and fail performing naming or copying tasks. Major differences in the overall rate of cognitive decline among PD patients support the co-existence of at least two patterns of involution, differentiating a relatively slow decline of fronto-striatal deficits from a more rapid decline of posterior–cortical deficits, with different pathophysiological substrates, genetics, prognosis and response to drugs used to treat the motor symptoms of PD.
Within the past few years, there has been a significant change in identifying and characterizing the FMR1 premutation associated phenotypes. The premutation has been associated with elevated FMR1 ...mRNA levels and slight to moderate reductions in FMRP levels. Furthermore, it has been established that approximately 20% of female premutation carriers present primary ovarian insufficiency (POI) and that fragile X-associated tremor/ataxia syndrome (FXTAS) occurs in one-third of all male premutation carriers older than 50 years. Besides POI and FXTAS, new disorders have recently been described among individuals (especially females) with the FMR1 premutation. Those pathologies include thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia. However there are few reports related to FXTAS penetrance among female premutation carriers or regarding these disorders recently associated to the FMR1 premutation. Therefore, we have evaluated 398 fragile X syndrome (FXS) families in an attempt to provide an estimation of the premutation associated phenotypes penetrance. Our results show that signs of FXTAS are detected in 16.5% of female premutation carriers and in 45.5% of premutated males older than 50 years. Furthermore, among females with the FMR1 premutation, penetrance of POI, thyroid disease and chronic muscle pain is 18.6, 15.9 and 24.4%, respectively. The knowledge of this data might be useful for accurate genetic counselling as well as for a better characterization of the clinical phenotypes of FMR1 premutation carriers.
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.
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