Serotonergic and Dopaminergic Lesions Underlying Parkinsonian Neuropsychiatric Signs.

Background: Parkinson's disease (PD) is characterized by heterogeneous motor and nonmotor manifestations related to alterations in monoaminergic neurotransmission systems. Nevertheless, the characterization of concomitant dopaminergic and serotonergic dysfunction after different durations of Parkinson's disease, as well as their respective involvement in the expression and severity of neuropsychiatric signs, has gained little attention so far.

Methods: To fill this gap, we conducted a cross-sectional study combining clinical and dual-tracer positron emission tomography (PET) neuroimaging approaches, using radioligands of dopamine ([ C]-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane) ([ C]PE2I) and serotonin ([ C]-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine) ([ C]DASB) reuptake, after different durations of Parkinson's disease (ie, in short-disease duration drug-naive de novo (n = 27, 0-2 years-duration), suffering from apathy (n = 14) or not (n = 13); intermediate-disease duration (n = 15, 4-7 years-duration) and long-disease duration, non-demented (n = 15, 8-10 years-duration) patients).

Toward a Sequential Strategy for Diagnosing Neurocognitive Disorders: A Consensus from the "Act On Dementia" European Joint Action.

Neurocognitive disorders causing progressive cognitive, functional, and behavioral impairment remain underdiagnosed. The needs for a timely diagnosis are now widely acknowledged since person-centered care helps to preserve life quality and prevent crises. One powerful barrier to detection in primary care is the lack of an easy-to-follow stepwise approach, grounded in evidence and consistent with high-quality specialty practice.

Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease.

Background: Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction.

Methods: We compared the morphological and microstructural architecture in gray matter using voxel-based morphometry and diffusion tensor imaging coupled with white matter tract-based spatial statistics in a multimodal imaging case-control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age-matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems.

Subthalamic nucleus stimulation effects on single and combined task performance in Parkinson's disease patients: a PET study.

Subthalamic nucleus deep brain stimulation (STN-DBS) represents one of the most efficacious treatments for Parkinson's disease, along with L-dopa therapy. The objective of the present work was to identify the cerebral networks associated with hand movement and speech production tasks performed alone and simultaneously, as well as the effects of STN-DBS on these profiles. Clinical, behavioral, and neuroimaging (oxygen 15-labeled water and Positron Emission Tomography) investigations were used to study single and combined performances of unilateral hand movements and speech production in 11 unmedicated individuals with PD, both off and on STN-DBS.

The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson's disease.

SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson's disease, without the confounding effects of antiparkinsonian treatment.

Emotional manifestations of PD: Neurobiological basis.

Neuropsychiatric symptoms are common and disabling in PD. Their neurobiological bases are complex, partly because of the disease itself and partly because of the dopaminergic treatment. The aim of this review is to focus on the emotional manifestations stemming from the neurodegenerative process itself.

Neural substrates of levodopa-responsive gait disorders and freezing in advanced Parkinson's disease: a kinesthetic imagery approach.

Gait disturbances, including freezing of gait, are frequent and disabling symptoms of Parkinson's disease. They often respond poorly to dopaminergic treatments. Although recent studies have shed some light on their neural correlates, their modulation by dopaminergic treatment remains quite unknown.

Stimulation of the pedunculopontine nucleus area in Parkinson's disease: effects on speech and intelligibility.

Improvement of gait disorders following pedunculopontine nucleus area stimulation in patients with Parkinson's disease has previously been reported and led us to propose this surgical treatment to patients who progressively developed severe gait disorders and freezing despite optimal dopaminergic drug treatment and subthalamic nucleus stimulation. The outcome of our prospective study on the first six patients was somewhat mitigated, as freezing of gait and falls related to freezing were improved by low frequency electrical stimulation of the pedunculopontine nucleus area in some, but not all, patients. Here, we report the speech data prospectively collected in these patients with Parkinson's disease.

Levodopa does not change cerebral vasoreactivity in Parkinson's disease.

The aim of this work was to study cerebral vasoreactivity to hypercapnia in Parkinson's disease (PD) before and after levodopa administration. The prospective study was conducted in 20 patients presenting with PD, using 3T blood oxygenation level-dependent (BOLD) functional MRI (fMRI) covering the whole brain. The hypercapnic stimulus was block-designed using carbogen inhalation, a gas mixture of 7% CO2 and 93% O2, before (OFF) and 60 minutes after administration of a suprathreshold (120%) therapeutic L-dopa dose (ON).

Levodopa effects on hand and speech movements in patients with Parkinson's disease: a FMRI study.

Levodopa (L-dopa) effects on the cardinal and axial symptoms of Parkinson's disease (PD) differ greatly, leading to therapeutic challenges for managing the disabilities in this patient's population. In this context, we studied the cerebral networks associated with the production of a unilateral hand movement, speech production, and a task combining both tasks in 12 individuals with PD, both off and on levodopa (L-dopa). Unilateral hand movements in the off medication state elicited brain activations in motor regions (primary motor cortex, supplementary motor area, premotor cortex, cerebellum), as well as additional areas (anterior cingulate, putamen, associative parietal areas); following L-dopa administration, the brain activation profile was globally reduced, highlighting activations in the parietal and posterior cingulate cortices.

Imaging gait disorders in parkinsonism: a review.

Gait difficulties--including freezing of gait--are frequent and disabling symptoms of advanced Parkinson's disease and other parkinsonian syndromes. They respond poorly to current medical and surgical treatments, making patient management very difficult. The underlying pathophysiology remains largely unknown.