Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP), plasma malondialdehyde and total antioxidative capacity (TAC), as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59) and a control group of neurologically normal subjects (n = 29), attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery), while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol) of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC) of patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis.
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PMID:Cognitive impairment and Alzheimer's disease: Links with oxidative stress and cholesterol metabolism. 1904 15

The purpose of this study was to investigate the neuropsychological correlates of pathological gambling (PG) in Parkinson's disease (PD). Fifteen patients with PD affected by PG (identified based on DSM-IV criteria; PD+PG) without clinically evident dementia were compared with 15 nondemented patients with PD not affected by PG (PD-PG). Two groups of patients with PD were matched for age, length of education, and gender. Clinical and neuropsychiatric features were assessed; several cognitive domains, mainly related to executive functions, were explored by means of standardized neuropsychological tasks. PD+PG and PD-PG did not differ on clinical and neuropsychiatric aspects. PD+PG patients performed significantly worse than PD-PG patients on cognitive tasks that evaluated visuo-spatial long-term memory and several frontal lobe functions. After Bonferroni correction, differences remained significant on the Frontal Assessment Battery (FAB) (P = 0.001), on phonological fluency task (P = 0.003), and on the Trail Making Test, part B minus part A (P = 0.002). Logistic regression analysis demonstrated that low scores on the FAB were the only independent predictor of PG (odds ratio, 27.9; 95% CI: 2.82-277.95, P = 0.004). The results indicate an association between PG and frontal lobe dysfunctions in nondemented patients with PD. Low scores on the FAB indicate patients with PD at high risk for PG.
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PMID:Cognitive dysfunctions and pathological gambling in patients with Parkinson's disease. 1920 72

Frontal cortex samples from frozen human brains were used to assess tissue respiration; content of mitochondria; mitochondrial oxygen uptake; activity of respiratory complexes and of mitochondrial nitric oxide synthase (mtNOS); content of cytochromes a, b, and c; oxidative damage (protein carbonyls and TBARS); and expression of Mn-SOD in patients with Parkinson disease (PD) and with dementia with Lewy bodies (DLB) in comparison with those of normal healthy controls. Brain cortex and mitochondrial O(2) uptake and complex I activity were significantly lower in PD and DLB, whereas mtNOS activity, cytochrome content, expression of Mn-SOD, mitochondrial mass, and oxidative damage were significantly higher in the frontal cortex in PD and DLB. The decreases in tissue and mitochondrial O(2) uptake and in complex I activity are considered the consequences of mitochondrial oxidative damage. The increases in mtNOS activity and in mitochondrial mass are interpreted as an adaptive response of the frontal cortex that involves increased NO signaling for mitochondrial biogenesis. The adaptive response would partially compensate for mitochondrial dysfunction in these neurodegenerative diseases and would afford a human evolutionary response to shortage of ATP in the frontal cortex.
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PMID:Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies. 1929 51

The rise in Infantile Autism, learning problems, cognitive decline with age, Alzheimer's, Parkinson's Diseases and the SIDS epidemic, has a common cause in the rising dietary deficit in Omega-3 brain-food. This paper suggests that aside from the wider concept of Autism Spectrum Disorders (ASD) and Pervasive Developmental Disorders (PDD), the rise in Infantile Autism (IA) in the last decade is the effect of deficient brain-food (Omega-3). The consequent delay of development prolongs the 2nd regressive event in infancy to pruning of the centre in the Medial Frontal Lobe System that connects Hippocampus and Cingulum. With a consequently defective Supplementary Motor Area (SMA), the Delayed Response Function is affected leading to persistent psychosis. Post-Pubertal Episodic Psychoses are associated with acute reduction of excitation, a risk of breakdown of circuitry, insufficient fill-in mechanisms, and silent spots. An acute psychosis occurs if the silent spots comprise of SMA. Only two brain areas have continuous neurogenesis, indicating their important functions: the Hippocampus and Olfactory Bulb that belongs to the Lateral Frontal Lobe System essential to survival. Concerned with necessity of action in response to the environment, it relies upon short-term memory and Acute Feedback Mechanisms influenced by emotion and motivation from the external world. In contrast, the Medial Frontal Lobe network is controlled by Feed-Forward Predictive Mechanisms related to storage of information. The Delayed Response Function is mastered at 7 months, when 2nd event occurs with pruning of axons and dendrites. An abolished or defective Delayed Response Function seriously incapacitates an individual: A defective "Social Brain" with an inability for conscious action and to communicate, predominates in IA. There is a near lack of speech, despite normal vision and hearing in the minority without marked adversity in pregnancy, at delivery or in infancy. I propose that the recent rise in IA despite no rise in adversity signifies a rising deficiency in brain-food. That this is so is suggested by a changing clinical picture: no Mental Retardation in an IA majority. Deficit in Olfaction is pathognomonic in schizophrenia since 30 yrs and distinguishes the Asperger Syndrome. If brain-food deficiency alone sufficiently prolongs pruning to cause absent activity in SMA in infancy, less mentally retarded IA from other causes might be observed. Deficit in brain-food was evident in the Sudden Infant Death Syndrome: birthweight averaged 200-300 g lower than sibs, Omega-3 levels in brainstem were lower than controls. Only 20 % SIDS died in first hypoxic episode, suggesting such episodes are more frequent than we imagined. Children with learning-behaviour problems have similarly depressed birthweight. A general deficiency in Omega-3 contributes to the lacking reduction in Schizophrenia, despite early puberty predominates. Olfactory Bulb is first affected in the Alzheimer's and Parkinson's Disease. Cognitive decline with age, Hippocampal dysfunctions rise markedly irrespective of disease, but the major mental illnesses and Infantile Autism in particular, benefit from "brain-food" that might also prevent a development of these disorders. To secure optimal brain function in the coming generations, there is a need to change the diet now from its emphasis on protein for body growth to food for the brain. This means there is a need to increase fish and sea food consumption.
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PMID:Infantile autism: a chronic psychosis since infancy due to synaptic pruning of the supplementary motor area. 1932 37

To date, few studies have utilized standardized measures to assess the neurobehavioral changes that can accompany deep brain stimulation (DBS) of the subthalamic nuclei (STN) for the treatment of Parkinson's disease (PD), yet behavioral changes are the most debated among practitioners. We evaluated behavior with the Frontal Systems Behavior Scale (FrSBe), which includes a large-scale normative sample for self- and collateral ratings and is particularly relevant to PD with subscales assessing Apathy, Disinhibition, and Executive Dysfunction. Data were collected from 16 (11 males) PD patients. All FrSBe subscale scores increased significantly when retrospective preoperative scores and current (postoperative) scores were compared. Self- and collateral FrSBe ratings were not significantly correlated with each other, though for both scores at least half of the group met criteria for a clinically significant level of symptoms postoperatively. No significant correlations were seen for collateral current FrSBE ratings with cognitive or motor variables. Higher self-ratings of behavior characteristic of apathy were related to higher self-ratings of depressive symptoms, and to a smaller decrease in antiparkinsonian medications following surgery. We propose that the standardized assessment of behavioral aspects of executive dysfunction adds information that is largely dissociable from the motor and cognitive assessment of function in PD patients undergoing STN DBS. In future, prospective standardized measurement of behavior may allow for better prediction of which patients will experience significant behavioral issues postoperatively.
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PMID:Behavioral effects of subthalamic deep brain stimulation in Parkinson's disease. 1966 45

There are currently no Food and Drug Administration-approved treatments for frontotemporal lobar degeneration (FTLD). The objectives of this study were to explore the tolerability of memantine treatment in FTLD and to monitor for possible effects on behavior, cognition, and function. Forty-three individuals who met clinical criteria for FTLD [21 with frontotemporal dementia (FTD), 13 with semantic dementia (SD), and 9 with progressive nonfluent aphasia (PA)] received 26 weeks of open-label treatment with memantine at a target dose of 20 mg daily. Concurrent treatment with acetylcholinesterase inhibitors was prohibited. Cognitive and functional outcome measures included the Mini Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog), clinical dementia rating-sum of boxes, Neuropsychiatric Inventory (NPI), Frontal Behavior Inventory, Executive Interview (EXIT25), Texas Functional Living Scale (TFLS), Geriatric Depression Scale, and Unified Parkinson's Disease Rating Scale-motor scale. Most subjects were able to tolerate the target dose of memantine. A transient improvement was observed on the total NPI score primarily in the FTD group. Variable declines were observed on the ADAS-cog, EXIT25, Frontal Behavior Inventory, NPI, TFLS, and UPDRS scores. The FTD and SD groups declined on most of the cognitive and behavioral outcome measures, but remained stable on the UPDRS, whereas the progressive nonfluent aphasia group remained relatively stable on the ADAS-cog, NPI, and TFLS, but declined on the UPDRS. Memantine was well-tolerated in these subjects. Future placebo-controlled trials of memantine in FTLD are warranted and may have greater power to detect behavioral and cognitive effects if focused on the FTD and SD clinical syndromes.
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PMID:An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration. 1981 61

Previous studies suggested that olfaction is normal in progressive supranuclear palsy (PSP). We applied the University of Pennsylvania Smell Identification Test (UPSIT) to 36 patients with PSP who scored more than 18 on the Mini Mental State Examination (MMSE), 140 patients with nondemented Parkinson's disease (PD) and 126 controls. Mean UPSIT scores in PSP were lower than in controls (P < 0.001) but higher than in PD (P < 0.001) after adjusting for age, gender, and smoking history. For patients with PSP, UPSIT scores correlated with MMSE (r = 0.44, P = 0.006) but not disease duration (P = 0.6), motor subscale of the Unified Parkinson's Disease Rating Scale (P = 0.2), or Frontal Assessment Battery (P = 0.5). The brains of six of the patients with PSP were examined postmortem and all revealed neurofibrillary tangles and tau accumulation in the rhinencephalon, although only three had hyposmia. Further prospective studies including patients with early PSP and PSP-P with postmortem confirmation might help clarify if smell tests could be useful when the differential diagnosis lies between PD and PSP.
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PMID:Hyposmia in progressive supranuclear palsy. 2020 27

Most cardinal motor signs in Parkinson's disease (PD) are more pronounced on one side than on the other. Unusually, one type of cardinal motor sign is found on one side while other motor signs are more pronounced on the contralateral side, the so-called dissociation of motor signs. The aims of this study were to determine the frequency of motor sign dissociation and to study the clinical characteristics of the dissociation group. To this end, clinical characteristics including the Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination, Non-Motor Symptom Questionnaire and Frontal Lobe Assessment Battery were analyzed for 411 patients during consecutive follow-up visits. Dissociation was noted in 29 (7.06%) of the 411 patients. Dissociation of tremor and rigidity-bradykinesia was the most common type of dissociation pattern (17/29). There were no significant differences in demographic factors and clinical profiles between the dissociation and control groups. We suspect that each cardinal motor sign is pathogenetically different. The presence of dissociation did not affect the natural history of PD.
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PMID:Dissociation of cardinal motor signs in Parkinson's disease patients. 2045 13

This article reports the severity and profile of neuropsychological impairment on a prevalent cohort of patients with a clinical diagnosis of either multiple system atrophy (n=372) or progressive supranuclear palsy (n=311) from the Neuroprotection and Natural History in Parkinson Plus Syndromes cohort. The Dementia Rating Scale and Frontal Assessment Battery were used to assess global cognition and executive dysfunction. For the Dementia Rating Scale impairment was observed in approximately 57% of the progressive supranuclear palsy group and 20% of the multiple system atrophy group. In the former, impairment in a single cognitive domain was observed in 40%, with the same number showing impairment in multiple domains, while in the latter the figures were 28.6 and 13.5%, respectively. On the Frontal Assessment Battery, impairment was observed in 62.0% of patients with progressive supranuclear palsy and 31.8% of those with multiple system atrophy. Although the progressive supranuclear palsy group performed worse overall, the cognitive profiles of the two groups on the Dementia Rating Scale subscales were identical, with the main impairment of the Initiation and Perseveration subscale. The impaired patients in the two groups were largely indistinguishable, qualitatively and quantitatively. Impairment was associated with greater age and clinical disability in both groups and was evident even in the early stages (22% in multiple system atrophy and 50% in progressive supranuclear palsy). Where a pathological diagnosis was available, the original clinical diagnosis was confirmed in the majority of cases, including those with significant cognitive impairment. The rate of impairment in those with a confirmed pathological diagnosis was comparable to that of the sample as a whole. These results demonstrate, in the largest prospectively recruited cohort of patients with progressive supranuclear palsy and multiple system atrophy studied to date, the existence of a cognitive profile similar to that previously reported in idiopathic Parkinson's disease. The results indicate a high level of cognitive impairment associated with progressive supranuclear palsy, but also point to comparable dysfunction in a substantial proportion of the patients with multiple system atrophy. Significant cognitive impairment appears consistent with a diagnosis of multiple system atrophy, even early in the disease, with important implications for diagnosis, research and management.
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PMID:Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. 2057 97

Cognitive dysfunction is an important aspect of Parkinson disease (PD) and is increasingly being examined in various large scale PD clinical studies. However, the sensitivity of some of the cognitive measures used for detecting change in cognitive status in early PD patients is not known nor is the relationship between cognitive outcome measures and other motor and non-motor disease characteristics and various demographic parameters in early PD patients. The current analysis of the NET-PD cohort (i.e., untreated patients) was undertaken to: 1) assess which (if any) baseline demographic parameters correlate with baseline cognitive measures and any potential change in cognitive measures over the 12-18 months evaluation period; 2) assess the extent to which cognitive measures employed (i.e., Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Frontal Assessment Battery (FAB) and Letter-Number Sequencing) are sensitive to change over time; 3) examine whether initiation of symptomatic therapy is associated with change in cognitive status. At baseline, NET-PD subjects had no significant impairment on the assessments employed. Only education and age were significant predictors of cognitive score at baseline. None of the summary measures were indicative of change in cognitive status over the 12-18 months of study. These results suggest either the cognitive domains examined are not affected in the population examined or that more sensitive measures of cognition than those currently employed may need to be considered for use in a large trial setting in which an early, highly educated PD population is studied.
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PMID:Predictors of cognitive outcomes in early Parkinson disease patients: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience. 2059 21


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