Dopaminergic modulation of memory and affective processing in Parkinson depression (original) (raw)
Related papers
European Journal of Neurology, 2005
In a randomized prospective multi-centre study, we evaluated the cognitive performances of a group of 41 non-demented patients, all with advanced Parkinson's disease (PD) and a current depressive episode, in whom the effects of pramipexole (PPX) and pergolide (PRG) in an add-on to L-dopa therapy were also studied and published with regard to motor symptoms of PD, motor complications and depression. The Trail Making Test, the Stroop test and four subtests (arithmetic, picture completion, digit symbols and similarities) of the Wechsler Adult Intelligence Scale-Revised were performed prior to and 8 months after the administration of either PPX or PRG. We found no statistically significant difference between the two tested drugs or between the first and the last visit in any of the above-listed neuropsychological tests. All patientsÕ motor outcomes significantly improved and we conclusively demonstrated the anti-depressive effect of PPX. The dissociation of dopaminomimetic effects on the different tested domains indicates that there are different pathological mechanisms of cognitive, motor and affective disturbances in advanced PD patients. In our non-demented group of fluctuating depressed PD subjects, both PPX and PRG administration in combination with L-dopa were safe in terms of the effect on cognitive performance.
Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression
Parkinson's Disease, 2015
Parkinson’s disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medicat...
Dopamine agonists in the treatment of non-motor symptoms of Parkinson’s disease: depression
European Journal of Neurology, 2008
Background: Psychiatric symptoms such as depression are common non-motor comorbidities of Parkinson's disease (PD). Depressive symptoms in patients with PD are a major complication that impairs quality of life independent of motor symptoms. The relationship between PD and comorbid depression is not completely understood. Methods and Results: Evidence suggests that both PD and depression may be mediated by degeneration of the dopaminergic system. Recent and ongoing research is exploring the potential role of dopamine agonists in the treatment of depressive symptoms in patients with PD. Conclusion: Experimental studies suggest a primary relationship and the importance of dopaminergic mechanisms in PD and depression. Patients with PD and depression might benefit from a global approach. Thus, treatment with dopamine agonists promises to reduce motor complications as well as depressive symptoms, avoiding multiple drug interactions as well as possible antidepressant medication side effects.
Drugs & Aging, 2015
Introduction Dopaminergic agonists (DAs) are widely used to treat motor symptoms in Parkinson's disease (PD). The differential effect of DAs on neuropsychiatric symptoms of PD has not been accurately studied. Materials and methods We performed a prospective cross-sectional study of 515 non-demented PD patients receiving treatment with pramipexole [n = 250, monotherapy or with levodopa (L-dopa)], ropinirole (n = 150, monotherapy or with L-dopa), or L-dopa (n = 115, monotherapy); all formulations were immediate release. Neuropsychiatric disturbances were assessed through the Neuropsychiatric Inventory (NPI). Groups were matched in terms of age, education, sex, disease severity (Hoehn and Yahr), disease duration, executive function, total L-dopa daily equivalent dose, and concomitant psychotropic medications (antidepressants, anxiolytics and antipsychotic agents). Results Patients on pramipexole showed significantly lower total NPI scores than patients on ropinirole (17.2 ± 11 vs. 20.9 ± 13, p = 0.015). Regarding the spectrum of neuropsychiatric symptoms, pramipexole was associated with significantly lower apathy scores than the L-dopa group (1.01 ± 1.7 vs. 1.87 ± 2.93, p = 0.02). The frequency of patients with clinically meaningful symptoms of apathy (NPI apathy scores C4) was significantly lower in the pramipexole group (11.2 %) than in the ropinirole (20.3 %) and L-dopa (23.8 %) groups (v 2 12.49, p = 0.002). No other significant differences were found in NPI subscores between groups. Conclusions This is the first head-to-head comparative study of the effect of DAs on neuropsychiatric disturbances in PD that has controlled the sample for the most important confounding factors. In comparable groups of patients, the use of pramipexole seems to be associated with a lower frequency and severity of apathetic symptoms. Key Points Neuropsychiatric symptoms are frequent in Parkinson's disease. Using the Neuropsychiatric Inventory (NPI), we compared the neuropsychiatric profile of 515 non-demented patients treated with different dopaminergic agonists or levodopa (L-dopa) in monotherapy matched for L-dopa daily equivalent dose, and we found differences only in apathy score. Patients on pramipexole showed significantly lower total apathy scores. Moreover, clinically meaningful symptoms of apathy were significantly lower in the pramipexole group (11.2 %) than in the ropinirole (20.3 %) and L-dopa (23.8 %) groups (p = 0.002).
Dopaminergic medication improves cognitive control under low cognitive demand in Parkinson’s disease
Neuropsychology, 2020
Dopamine agonists are the main pharmacological intervention for the motor symptoms of Parkinson's disease (PD). However, dopaminergic medication has been associated with disinhibitory psychopathology in some patients. The aim of this study was to test the effect of dopaminergic medication on inhibitory control in patients with PD using the paced Random Number Generation task (RNG), which requires inhibition of pre-potent counting in series to produce a random sequence of numbers. Methods Twenty-three PD patients performed RNG on-and off-dopaminergic medication. Cognitive load was manipulated by performing RNG at faster (1Hz) and slower (0.5 Hz) rates. For RNG, two scores (CS1 and CS2) were derivedwhich are considered indices of more automatic and more controlled counting respectively. Results There were no main effects of medication on RNG performance. There was a significant main effect of cognitive load on CS1, with higher CS1 scores at the faster rate (p = <.01). A significant interaction effect between medication and rate (cognitive load) (p = .03) followed by post-hoc testing, revealed that CS2 scores were higher, on-medication, at the slower but not the faster rate. Conclusions Patients with PD displayed increased use of more controlled processing strategies onmedication at the slowest rate of RNG. Therefore, while dopaminergic medication has been associated with disinhibitory psychopathology, our results suggest that dopamine therapy may enhance some forms of inhibitory cognitive control in PD, but only there is sufficient time to engage controlled processing strategies.
European Journal of Neurology, 2013
Background and purpose: The investigation of the relationship between affective symptoms and dopamine transporter (DAT) density provided conflicting data in both Parkinson's disease (PD) and non-PD patients. However, the potential interference of psychoactive as well as anti-parkinsonian drugs on DAT density should be taken into account. Objective: To investigate the relationship between affective symptoms and presynaptic dopaminergic function in de novo PD patients. Methods: Forty-four de novo PD consecutive outpatients were recruited, and the severity of anxious symptoms was evaluated with the Hamilton Anxiety Rating Scale (HAM-A), the severity of depressive symptoms with the Hamilton Depression Scale (HAM-D) and the Beck Depression Inventory (BDI). Six patients had a formal diagnosis of depression. All patients performed 123 I-FP-CIT SPECT, and semi-quantitative striatal indices were calculated. Results: Disease severity, as measured by Unified Parkinson's Disease Rating Scale (UPDRSIII), was inversely correlated with bilateral striatal indices. Bilateral striatal uptake was significantly positively correlated with HAM-D (r.329; r.423, respectively, right and left), BDI (r.377; r.360, respectively, right and left) and HAM-A (r.338; r.340, respectively, right and left). After controlling for age, disease duration and severity, and Mini Mental State Examination (MMSE), no significant reduction in r-values was observed (P < 0.05). Conclusion: Our data support the existence of a relationship between depressive and anxious symptoms and the striatal 123 I-FP-CIT uptake. The finding of an increased DAT density associated with mild affective symptoms could be due to the lack of compensatory mechanisms usually present in early PD, and/or it might have a pathogenic role in affective symptoms by reducing the dopaminergic tone in the synaptic cleft.
Differential role of dopamine in emotional attention and memory: evidence from Parkinson's disease
Movement disorders : official journal of the Movement Disorder Society, 2011
Consistent with the hypothesis that dopamine is implicated in the processing of salient stimuli relevant to the modification of various behavioral responses, Parkinson's disease is associated with emotional blunting. To address the hypothesis that emotional attention and memory are modulated by dopaminergic neurotransmission in Parkinson's disease, we assessed 15 nondemented patients with Parkinson's disease while on and off dopaminergic medication and 15 age-matched healthy controls. Visual stimuli were presented, and recognition was used to assess emotional memory. Response latency was used as a measure of emotional attention modulation. Stimuli were varied based on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Controls had significantly better memory for positive than negative stimuli, whereas patients with Parkinson's disease tested off medication had significantly better memory for negative than positive items. This negat...
Journal of Neuropsychiatry, 2010
Depression is associated with more rapid cognitive decline in Parkinson's disease (PD). The goal of this study was to examine the impact of the acute (8-week) and longer-term (24-week) antidepressant treatment on cognition in PD and to detail cognitive predictors of treatment response. Fifty-two depressed PD patients were enrolled in an NIH funded randomized-controlled trial of nortriptyline, paroxetine, and placebo. Neuropsychological testing was performed at baseline, and weeks eight and twenty-four. Higher baseline scores on measures of executive functioning, speed of processing, and verbal memory were associated with antidepressant response. Treatment responders did not exhibit larger gains in cognition than non-responders. Findings warrant replication.
Parkinson's disease and depression
Brain, 1986
The possibility of an 'organically' based depression intrinsic to the pathophysiology of Parkinson's disease (PD) and comparable to endogenous depression (Major Depressive Episode) has been raised. It has also been argued that signs of depression observed in PD are merely the natural reaction of the patients to their progressive and inevitable physical limitations and loss of independent function. Because conventional depression rating scales are limited in scope, a psychometric investigation of depression in PD was pursued. Based on the known impairment of short-term memory (STM) in endogenous depression, which was confirmed in a group of psychiatric patients in the present study, measures of STM were also obtained in groups of depressed and nondepressed PD patients and in 15 normal control subjects. Regardless of depression severity, PD patients performed as well as control subjects and both these groups consistently obtained scores significantly better than those of the endogenously depressed patients. A relative weakness in the PD patients on order-dependent STM tests was further explored and interpreted as an indication of mild frontal lobe dysfunction. It was concluded that PD patients are frequently depressed when confronted with their behavioural limitations and that this reaction may be exacerbated by a form of emotional lability related to pathophysiological processes which may involve prefrontal cortical areas.