Previous studies have failed to distinguish the differential contribution of major and minor depression to cognitive impairment in patients with idiopathic Parkinson's disease (PD). This study was aimed at investigating the relationships among major depression (MD), minor depression (MiD) and neuropsychological deficits in PD. Eighty-three patients suffering from PD participated in the study. MD and MiD were diagnosed by means of a structured interview (SCID-I) based on the DSM-IV criteria, and severity of depression was evaluated by the Beck Depression Inventory. For the neuropsychological assessment, we used standardized scales that measure verbal and visual episodic memory, working memory, executive functions, abstract reasoning and visual-spatial and language abilities. MD patients performed worse than PD patients without depression on two long-term verbal episodic memory tasks, on an abstract reasoning task and on three measures of executive functioning. The MiD patients' performances on the same tests fell between those of the other two groups of PD patients but did not show significant differences. Our results indicate that MD in PD is associated with a qualitatively specific neuropsychological profile that may be related to an alteration of prefrontal and limbic cortical areas. Moreover, the same data suggest that in these patients MiD and MD may represent a gradual continuum associated with increasing cognitive deficits.
"Previous findings in PD patients have shown an association between on/off states, fluctuations of mood and anxiety symptoms , and a potential negative influence of affective disorders on cognitive performance  . Therefore, the State and Trait Anxiety Inventory-State Anxiety (STAY-S)  and the Beck Depression Inventory (BDI)   were administered to both PD and healthy participants in the two experimental sessions. "
[Show abstract][Hide abstract] ABSTRACT: previous data suggest that i) dopamine modulates the ability to implement non-routine schemata and updating operations (flexibility processes) and that ii) dopamine-related improvement may be related to baseline dopamine levels in target pathways (inverted U-shaped hypothesis).
to investigate above hypotheses in individuals with Parkinson's disease (PD).
twenty PD patients were administered tasks varying as to flexibility load in two treatment conditions: i) "off" condition, about 18~hours after dopamine dose; ii) "on" condition, after dopamine administration. PD patients were separated into two groups: low performers (i.e., performance on Digit Span Backward below the sample mean) and high performers (i.e. performance above the mean). Twenty healthy individuals performed the tasks in two sessions without taking drugs.
passing from the "off" to the "on" state, only low performer PD patients significantly improved their performance on high-flexibility measures (interference condition of the Stroop test; p< 0.05); no significant effect was found on low-flexibility tasks.
these findings document that high-flexibility processes are sensitive to dopamine neuromodulation in the early phases of PD. This is in line with the hypothesis that striatal dopamine pathways, affected early by PD, are precociously implicated in the expression of cognitive disorders in these individuals.
"Apathy, depression, and anxiety are present in one-third of PD patients (Aarsland et al., 2009b). Major depression in PD has been associated with deficits in some cognitive domains, specifically memory, and EFs (Kuzis et al., 1997; Norman et al., 2002; Costa et al., 2006), presumably as a consequence of difficulty in mobilizing cognitive resources to complete tasks (Hasher and Zacks, 1979; Zakzanis et al., 1998). Varanese et al. (2011) reported that apathy, but not depression, was associated with specific disorders of recall and EFs in PD subjects. "
[Show abstract][Hide abstract] ABSTRACT: This mini-review summarizes the evidence of the cognitive and behavioral features of dysexecutive syndrome in Parkinson's disease (PD). Deficits in response inhibition, set-shifting, mental flexibility, and strategy have been frequently described from the earliest stages of PD, although there are inconsistencies in study findings due to the complexity of the executive function (EF) construct and methodological limitations. Behavioral disorders of PD, e.g., apathy, distractibility, perseverative behavior, and impulse-control disorders, may be viewed as the other side of dysexecutive syndrome. Despite the interrelationship between the cognitive and behavioral domains, some reports reveal that the two syndromes may be dissociated, suggesting that both aspects must be clinically assessed. EFs are widely associated with the prefrontal areas, although dysexecutive syndrome may be observed in patients with damage to other brain regions. EFs drive numerous abilities essential to daily life, such as prospective remembering and language comprehension, which may be impaired in PD subjects. Considering the impact of dysexecutive syndrome on independence and quality of life, early detection of executive impairment is crucial in the management of PD.
Frontiers in Neurology 11/2012; 3:159. DOI:10.3389/fneur.2012.00159
"Please cite this article in press as: Sánchez, M.G., et al., Estradiol modulation of cortical, striatal and raphe nucleus 5-HT 1A and..., Neuropharmacology (2010), doi:10.1016/j.neuropharm.2010.11.024 was investigated because of the modulation 5-HT 2A receptors by estradiol in this brain region in rats (Cyr et al., 1998) and the role of serotonin in the frontal cortex in depression (Costa et al., 2006). Samples of the anterior cerebral cortex from levels ac þ12 mm, anterior striatum from levels ac þ3 mm and raphe from levels ac À12 mm according to the atlas of Martin and Bowden (2000) were therefore investigated. "
[Show abstract][Hide abstract] ABSTRACT: Depression is common in Parkinson's disease and an imbalance in serotonin neurotransmission could be implicated. Estradiol is reported to modulate brain serotonin systems of rodents and monkeys, but this has not been explored in primate models of Parkinson's disease. Thus, the present study investigated the effect of estradiol on 5-HT(1A) and 5-HT(2A) serotonin receptors in the cortex, striatum and raphe nucleus of long-term ovariectomized hemiparkinsonian monkeys. Seven monkeys were ovariectomized and received a month later a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Four years after lesion and ovariectomy, three received a month of treatment with 17β-estradiol and four the vehicle. Autoradiography of [(3)H]8-OH-DPAT specific binding to 5-HT(1A) receptors showed a decrease in the frontal cortex of monkeys treated with 17β-estradiol in both hemispheres of the brain. [(3)H]ketanserin specific binding to 5-HT(2A) receptors was increased in the frontal cortex and the striatum of monkeys treated with 17β-estradiol in both the lesioned and intact sides of the brain. Autoradiography of [(35)S]GTPγS specific binding stimulated with R-(+)-8-OH-DPAT showed a decrease in the percentage of stimulation in the frontal cortex of monkeys treated with 17β-estradiol in both hemispheres of the brain and in the dorsal raphe nucleus. Treatment with 17β-estradiol was initiated a long time after ovariectomy in monkeys to model post menopausal hormonal conditions and showed that serotonin receptors were still responsive in the brain regions investigated. These results support a role for 17β-estradiol on serotonin activity in Parkinson's disease and could be useful for treatment of depression associated with this disease.
Christine Thai, Yen Ying Lim, Victor L Villemagne, Simon M Laws, David Ames, Kathryn A Ellis, Stephanie R Rainey-Smith, Ralph N Martins, Colin L Masters, Christopher C Rowe, Paul Maruff
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