The spectrum of neuropsychiatric symptoms in patients with early untreated Parkinson's disease

Aarsland, Dag; Brønnick, Kolbjørn; Alves, Guido; Tysnes, Ole‐Bjørn; Pedersen, Kenn Freddy; Ehrt, Uwe; Larsen, Jan Petter

doi:10.1136/jnnp.2008.166959

Cited by 267 publications

(196 citation statements)

References 16 publications

(14 reference statements)

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“…The most common symptoms reported in this study were depression (37%), apathy (27%), sleep disturbance (18%) and anxiety (17%), whereas, psychotic symptoms were found to be very rare among untreated PD patients [15]. In PD patients with dementia the prevalence of neuropsychiatric symptoms was found to be higher.…”

Section: Resultsmentioning

confidence: 51%

“…A more recent study [15] found that the prevalence of neuropsychiatric symptoms in early untreated PD patients was 56%. The most common symptoms reported in this study were depression (37%), apathy (27%), sleep disturbance (18%) and anxiety (17%), whereas, psychotic symptoms were found to be very rare among untreated PD patients [15].…”

Section: Resultsmentioning

confidence: 96%

“…Depression is the most common neuropsychiatric symptom in PD patients [15]. It has been indicated that the prevalence rate of depression in this disease is approximately 40% [14,20,21].…”

Section: Depressionmentioning

confidence: 99%

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Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

Alzahrani

Venneri

2015

Journal of the Neurological Sciences

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Section: Resultsmentioning

confidence: 51%

Section: Resultsmentioning

confidence: 96%

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Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

Alzahrani

Venneri

2015

Journal of the Neurological Sciences

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“…Baseline clinical data demonstrate the expected increase in the MDS‐UPDRS in PD compared to HC subjects. Comparison of MoCA scores between PD and HC subjects is limited since HC subjects were not eligible if MoCA was <27, but approximately 20% of PD subjects had a baseline MoCA <26 consistent with early cognitive impairment 40, 41, 42. Furthermore, testing for depression, anxiety, and autonomic function demonstrate impairment in PD compared to HC subjects.…”

Section: Discussionmentioning

confidence: 99%

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Marek

Chowdhury

Siderowf

et al. 2018

Ann Clin Transl Neurol

399

339

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ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker‐defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease‐modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS‐UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α‐synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t‐tau (45/53) and p‐tau (16/18) were reduced in PD versus HC (P < 0.01),Interpretation PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

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“…In early untreated PD, anxiety and apathy are common 66, implying that these two mood disturbances are also part of a spectrum of ‘hypodopaminergy’ in the same way as depression. Amongst the imaging studies of the three mood disturbances, the majority used one single imaging modality and ROI analytical strategies.…”

Section: Methodsmentioning

confidence: 99%

Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies

Wen

Chan

Tan

et al. 2016

Euro J of Neurology

148

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Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer‐reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single‐photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal−limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre‐processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra‐nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

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The spectrum of neuropsychiatric symptoms in patients with early untreated Parkinson's disease

Cited by 267 publications

References 16 publications

Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies

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