Fat-soluble vitamin therapy in senile dementia and Parkinson's disease

In the pathogenesis of Parkinson's disease and senile dementia of the Alzheimer type, free radicals might play a role. Fat-soluble vitamins are a kind of anti-oxidative substance. Therefore, fat-soluble vitamins, such as vitamin E, may be useful in treatment of Parkinson's disease and senile dementia of the Alzheimer type. However, it is still unclear whether the concentration of vitamin E in the blood or in the brain tissue, in patients with Parkinson's disease or with of the senile dementia Alzheimer type, is higher than or the same as that in normal subjects. Furthermore, although the effectiveness of vitamin E in the treatment of Parkinson's disease has been reported, the usefulness of vitamin E is still obscure. Further study will be necessary, in order to clarify the role of fat-soluble vitamins in the treatment of Parkinson's disease and senile dementia of the Alzheimer type.     

Reduction of dopamine synaptic activity: Degradation of 50-khz ultrasonic vocalization in rats.

Vocal deficits are prevalent and debilitating in Parkinson's disease. These deficits may be related to the initial pathology of the nigrostriatal dopamine neurons and resulting dopamine depletion, which contributes to dysfunction of fine motor control in multiple functions. Although vocalization in animals and humans may differ in many respects, we evaluated complex (50-kHz) ultrasonic mate calls in 2 rat models of Parkinson's disease, including unilateral infusions of 6-hydroxydopamine to the medial forebrain bundle and peripheral administration of a nonakinesia dose of the dopamine antagonist haloperidol. We examined the effects of these treatments on multiple aspects of the acoustic signal. The number of trill-like (frequency modulated) 50-kHz calls was significantly reduced, and appeared to be replaced by simpler (flat) calls. The bandwidth and maximum intensity of simple and frequency-modulated calls were significantly decreased, but call duration was not. Our findings suggest that the nigrostriatal dopamine pathway is involved to some extent in fine sensorimotor function that includes USV production and complexity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning and forgetting processes in Parkinson's disease: a model-based approach to disentangling storage, retention and retrieval contributions

Learning and forgetting a prose passage was studied in 20 patients with Parkinson's disease and in 20 normal control subjects by means of stochastic models, with the aim of identifying the learning and retaining abilities that are affected by Parkinson's disease. Results suggested that Parkinson's disease patients are impaired in developing automatic processing both during learning and retaining, while functions that require active attention are spared. The automatic/intentional dissociation, which is the hallmark of motor disturbance in Parkinson's disease, extends to memory abilities, and, on the grounds of neuroanatomical, neurochemical and neurophysiological correlates, suggests that the memory deficit in Parkinson's disease may be contingent on a dysfunction of the medial prefrontal-cingulate cortex.     

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.     

Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigral neurons

In Parkinson's disease and other Lewy-body-associated disorders, the substantia nigra pars compacta undergoes degeneration, but the mechanism of cell death has not been previously described. The substantia nigra of normal and Alzheimer's disease cases were compared with substantia nigra from patients with Lewy-body-associated disorders (Parkinson's disease, concomitant Alzheimer's/Parkinson's disease, and diffuse Lewy body disease) using in situ end labeling to detect fragmented DNA. In situ end-labeled neurons demonstrated changes resembling apoptosis: nuclear condensation, chromatin fragmentation, and formation of apoptotic-like bodies. Ultrastructural analysis confirmed nuclear condensation and formation of apoptotic-like bodies. Apoptotic-like changes were seen in the substantia nigra of both normal and diseased cases; concomitant Alzheimer's/Parkinson's disease and diffuse Lewy body disease cases had significantly higher amounts of apoptotic-like changes than normal controls or Alzheimer patients. The finding of neuronal death by apoptosis may have relevance for the development of new treatment strategies for Parkinson's disease and related disorders.     

Iodine-123-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iod ophenyl)tropane SPECT in healthy controls and early-stage, drug-naive Parkinson's disease

The aims of this study were to investigate whether the loss of striatal dopamine transporters in early and drug-naive patients with Parkinson's disease could be demonstrated by means of 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)tropane (123I-FP-CIT) SPECT in a 1-day protocol and whether the SPECT measures were correlated with disease severity. METHODS: Twenty-one early-stage and drug-naive Parkinson's disease patients (age range 42-73 yr; mean age 55.5 yr) and 14 healthy controls (age range 28-83 yr; mean age 53.6 yr) were examined. SPECT image acquisition was always performed at 3 hr postinjection. The ratio of specific to nonspecific striatal 123I-FP-CIT binding was used as the outcome measure. RESULTS: All striatal 123I-FP-CIT ratios were significantly lower in the Parkinson's disease group compared to those in the control group. The mean reduction in the putamen was 57% of the control mean, and that in the caudate nucleus was 29% of the control mean. Patients with unilateral Parkinson's disease showed a bilateral loss of striatal 123I-FP-CIT binding. Discriminant function analysis, using the 123I-FP-CIT SPECT data of the ipsilateral and contralateral putamen, predicted group membership in all cases; the contralateral putamen accounted for the greatest difference between the Parkinson's disease patients and the controls. In the control group, a clear decline in 123I-FP-CIT binding was found with aging, amounting to 9.6%/decade. Unexpectedly, in the Parkinson's disease group, regression analysis revealed that neither severity of disease nor age accounted for a significant part of the variance in striatal SPECT measures. CONCLUSION: Our findings indicate that 123I-FP-CIT SPECT is a reliable method to discriminate between early, drug-naive Parkinson's disease patients and healthy controls and to identify patients in the preclinical phase of Parkinson's disease. Possibly due to the relatively homogeneous group of Parkinson's disease patients and the use of a suboptimal outcome measure, no significant correlations were found between striatal 123I-FP-CIT binding ratios and disease severity, such as were established earlier with 123I-beta-CIT. Further research is necessary to interpret these findings.     

Twenty-four-hour blood pressure profile and blood pressure responses to head-up tilt tests in Parkinson's disease and multiple system atrophy

OBJECTIVE: To investigate the 24 h blood pressure profile in patients with Parkinson's disease with intact autonomic function or with autonomic failure and patients with multiple system atrophy (MSA), and to assess whether these patients exhibit posture-related variations in blood pressure. PATIENTS AND METHODS: We studied 24 patients with Parkinson's disease (11 with autonomic failure) and 13 patients with MSA (all with autonomic failure). Autonomic failure was determined by autonomic tests. An oscillometric recorder was used for ambulatory blood pressure monitoring. Tilt-table tests were performed with a head-up tilt position of 60 degrees. RESULTS: An alteration in the normal 24 h blood pressure profile was observed in 82% of Parkinson's disease patients with autonomic failure and in 85% of those with multiple system atrophy, but not in the patients with intact autonomic function. Head-up tilt tests revealed a significantly higher supine blood pressure in Parkinson's disease patients with autonomic failure and in those with MSA than in Parkinson's disease patients with intact autonomic function. Tilting resulted in a marked fall in blood pressure in patients with MSA; in Parkinson's disease patients with autonomic failure, the fall was comparatively slighter. CONCLUSIONS: We conclude that autonomic failure contributes to the alterations in the day-night blood pressure profile that may possibly be ascribed to postural dysregulation of blood pressure. We hypothesize that nocturnal hypertension is a risk factor in the development of additional cerebrovascular disease in patients with Parkinson's disease or MSA who are affected by autonomic failure.     

Developmental subtypes of juvenile bipolar disorder

The incidence of hip fractures has increased over the past decades, and for patients with hip fractures, medical and social conditions have deteriorated during the same time. In this study the results of orthopaedic rehabilitation of patients with Parkinson's disease and a hip fracture are compared with those in all other hip fracture patients. A total of 74 patients with Parkinson's disease and hip fracture were compared with 1,361 patients without the disease. Prior to fracture, patients with Parkinson's disease were less likely to be living an independent life in their own homes. Postoperatively women with Parkinson's disease were hospitalized for a significantly longer period. Postoperative rehabilitation was significantly slower and less successful than among patients without the disease. Patients with Parkinson's disease comprise a subgroup of hip fracture patients who need more rehabilitation resources than can easily be provided at an ordinary orthopaedic ward. A team-work between an orthopaedic surgeon, a neurologist and a rehabilitation unit seems to be mandatory in order to achieve shorter hospitalization and earlier return to the pre-fracture environment.     

Recognition by familiarity is preserved in Parkinson's without dementia and Lewy-Body disease.

Objective: The retrieval deficit hypothesis states that the lack of deficit in recognition often observed in patients with Parkinson's disease is because of the low retrieval requirements of the task, given that these patients have retrieval and not encoding deficits. To test this hypothesis we investigated recognition memory by familiarity in Parkinson's patients and in patients with Lewy Bodies disease and Parkinson with dementia. Method: We analyzed to what extent the experimental groups were able to recognize by familiarity in a typical yes/no recognition memory task. The experimental groups were patients with early nondemented Parkinson's disease, advanced nondemented Parkinson's disease, demented Parkinson's patients, and patients with dementia with Lewy Bodies. We compared their performance with a group of young and another group of old healthy participants. The estimation of familiarity was made by analyzing recognition of word targets and distractors consisting of combinations of different letters in comparison with a condition in which targets and distractors were composed of similar letters, even though subjects were unaware of the independent variable. Results: The results indicate that familiarity was used at the same level by controls, patients with early Parkinson's disease and patients with dementia with Lewy Bodies. Although late Parkinson patients also used familiarity, its effect was only marginally significant. Patients with Parkinson's disease and dementia were not capable of using familiarity in recognition memory. Conclusions: Our results support the retrieval deficit hypothesis as Parkinson's patients without dementia show no deficit in a situation in which the retrieval requirements are minimal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Automimmune response to dopamine-receptor as a possible mechanism in the pathogenesis of Parkinson's disease and schizophrenia

Clinical and neuropharmacological evidence indicates the involvement of dopaminergic mechanisms in Parkinson's disease and schizophrenia, as well as in iatrogenic Parkinsonism and drug-induced schizophrenia-like syndrome. The evidence hitherto presented stresses the existence of a reversed relationship between Parkinson's disease and schizophrenia and implicates the possibility that dysfunction of dopamine-receptors may be a central phenomenon in both diseases. In view of the recent demonstration of two separate dopamine-receptors, it is postulated that a striatal receptor blockade may cause Parkinson's disease, whereas a limbic receptor blockade may result in schizophrenia. The recent discovery that several autoimmune diseases, such as myasthenia gravis, are the result of an immunopharmacological block at receptor sites, together with several observations of immunological disorders in Parkinson's disease and schizophrenia, suggests the possibility that certain types of Parkinson's disease and schizophrenia might be the consequence of an autoimmune blockade of striatal or limbic dopamine-receptors, respectively.     

Postprandial hypotension and orthostatic blood pressure responses in elderly Parkinson's disease patients

OBJECTIVE: To investigate the change in systolic blood pressure (SBP) induced by meals and to compare their impact on the orthostatic SBP response in elderly Parkinson's disease with that in control patients. DESIGN: Ten elderly patients suffering from Parkinson's disease were compared with 10 age-matched elderly control patients. METHODS: The postprandial SBP change was measured by means of ambulatory blood pressure monitoring with the patient in the supine position. Orthostatic SBP responses were measured the next day by means of active standing and passive head-up tilting tests performed before and after the patients had their lunch. RESULTS: In Parkinson's disease patients, a postprandial SBP drop of 27 mmHg in the supine position was found compared with a drop of 8 mmHg in controls. In Parkinson's disease patients, that drop was moderately correlated to the orthostatic SBP responses and significantly correlated to the preprandial supine baseline SBP level. The orthostatic fall in SBP was greater with passive than with active standing and with both it was greater in Parkinson's disease patients than in the control subjects. The fall in orthostatic blood pressure was reduced by a previous meal. In contrast, there was no difference in orthostatic heart rate responses between the patients and the controls. CONCLUSIONS: Parkinson's disease patients demonstrated a significant postprandial drop in SBP and a tendency towards orthostatic hypotension, which was not worsened by the meal, probably owing to a stronger sympathetic activation. Postprandial supine SBP change and orthostatic SBP responses were only moderately associated in Parkinson's disease patients. In addition to autonomic dysfunction, an increased baseline SBP level might contribute to both phenomena.     

Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation

The presynaptic protein alpha-synuclein has been implicated in the pathogenesis of Parkinson's disease. First, two missense mutations A30P and A53T cause inheritable early onset Parkinson's disease in some families. Secondly, alpha-synuclein is present in Lewy bodies of affected nerve cells in the predominant sporadic type of Parkinson's disease as well as in dementia with Lewy bodies. We demonstrate in the rat optic system that a portion of alpha-synuclein is carried by the vesicle-moving fast component of axonal transport and that it binds to rat brain vesicles through its amino-terminal repeat region. We find alpha-synuclein with the A30P mutation of familial Parkinson's disease devoid of vesicle-binding activity and propose that mutant alpha-synuclein may accumulate, leading to assembly into Lewy body filaments.     

Bone morphogenetic protein receptors

The relationship between physical trauma and Parkinson's disease is reviewed. Post-traumatic Parkinson's syndrome may occur following cumulative head trauma in contact sports and exceptionally rarely after single severe closed head injury. It remains uncertain, however, whether physical injury should be considered one aetiological factor in the pathogenesis of Parkinson's disease.     

Decreased beta-phenylethylamine in CSF in Parkinson's disease

OBJECTIVE: To determine the concentrations of beta-phenylethylamine (PEA) in CSF in patients with Parkinson's disease, and to evaluate the relation between concentration of PEA in CSF and severity of Parkinson's disease. METHODS: Using gas chromatography-chemical ionisation mass spectrometry, CSF concentrations of PEA were measured in 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2) years), of whom three were at Hoehn and Yahr stage II, 11 were at stage III, and nine were at stage IV. Comparison was made with eight patients with neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controls without neurological disease (mean age, 57.6 (SD 4.8) years). RESULTS: Concentrations of PEA in CSF in Parkinson's disease were significantly lower (mean 205 (SD 131) pg/ml) than in patients with peripheral neuropathy (433 (SD 254) pg/ml) and controls (387 (SD 194) pg/ml). The concentrations of PEA in CSF correlated negatively with Hoehn and Yahr stage (P<0.01). CONCLUSIONS: There are decreased CSF concentrations of PEA in patients with Parkinson's disease.     

Concentrations of vitamins A, C and E in elderly patients with Parkinson''s disease

Concentrations of the naturally occurring antioxidant vitamins A, C and E were measured in 27 patients with Parkinson's disease and 16 age-matched control subjects, from a similarly disabled patient group. There was no significant difference in the serum concentrations of vitamins A and E in the two groups. Vitamin C was significantly higher (P < 0.05) in the Parkinson's disease group, however, the mean leucocyte vitamin C concentration in the control group was low (101 nmol/10(8) WBCS) compared to established data in healthy young individuals (119-301 nmol/10(8) WBCS). There was no correlation between the severity or duration of Parkinson's disease and concentrations of vitamins A, C and E. There is therefore no evidence from this study that a deficiency of these antioxidants contributes to the onset or progress of Parkinson's disease.     

Magnetic field exposure and cardiovascular disease mortality among electric utility workers

Glial cell line-derived neurotrophic factor (GDNF) was identified as a consequence of the hypothesis that glia secrete factors that influence growth and differentiation of specific classes of neurons. Glia are a likely source of additional neurotrophic factors; however, this strategy has not been applied extensively. The discovery of GDNF in 1993 led to an abundance of studies that within only a few years qualified GDNF as a bona fide neurotrophic factor. Of particular interest are studies demonstrating the effectiveness of GDNF protein in ameliorating neurodegeneration in animal models of Parkinson's disease and amyotrophic lateral sclerosis (ALS). It remains to be determined whether GDNF will be an effective therapy in humans with these diseases. However, since these diseases are slowly progressive and the CNS relatively inaccessible, the delivery of GDNF as a therapeutic molecule to the CNS in a chronic manner is problematic. Studies addressing this problem are applying viral vector mediated transfer of the GDNF gene to the CNS in order to deliver biosynthesized GDNF to a specific location in a chronic manner. Recent studies suggest that these GDNF gene therapy approaches are effective in rat models of Parkinson's disease. These studies are reviewed in the context of what developments will be needed in order to apply GDNF gene therapy to the clinic.     

The role of NMDA receptors in the slow neuronal degeneration of Parkinson's disease

Parkinson's disease is a disorder, in which neurons of various neuronal systems degenerate. Furthermore, in such degenerating neurons, the cytoskeleton seems to be affected. In this respect, Parkinson's disease resembles Alzheimer's disease. Since it has been shown, that elevated levels of intracellular calcium can disrupt the cytoskeleton and that the stimulation of glutamate (NMDA) receptors can cause high intracellular concentrations of calcium, it has been suggested, that the stimulation of glutamate receptors plays a role in the slow degeneration in Alzheimer's and Parkinson's disease. In case of the degeneration of the dopaminergic nigrostriatal system in Parkinson's disease, neurons that contain calcium binding protein appear to be less vulnerable than the neurons that lack it, suggesting that calcium binding protein might protect these neurons from degeneration by preventing that cytosolic calcium concentrations increase excessively. And, since there is in the nigrostriatal system a glutamatergic afferent pathway (the prefrontonigral projection) and since dopaminergic nigrostriatal neurons contain postsynaptic NMDA receptors, glutamatergic excitation may play a role in the degeneration of the nigrostriatal system in Parkinson's disease. If so, it may be possible to protect the neurodegeneration of these dopaminergic neurons by NMDA receptor antagonists.     

Test/retest reproducibility of iodine-123-betaCIT SPECT brain measurement of dopamine transporters in Parkinson's patients

Iodine-123-beta-CIT has been used as a probe of dopamine transporters in Parkinson's disease patients using SPECT. We studied the test/retest reproducibility of SPECT measures in Parkinson's disease patients and healthy controls obtained after injection of [123I])beta-CIT in part to assess the utility of this tracer for longitudinal evaluation of striatal dopamine transporters as a marker of disease progression. METHODS: Seven Parkinson's disease patients and seven healthy control subjects participated in two [123I]beta-CIT SPECT scans separated by 7-21 days. Subjects were imaged at 24 hr post injection of 360 MBq (9.7 mCi) of [123I]beta-CIT. Two outcome measures were evaluated; 1) the ratio of specific striatal (activity associated with DA transporter binding) to nondisplaceable uptake, also designated V3," and 2) the total specific striatal uptake (%SSU) expressed as a percentage of injected radiotracer dose. For both measures, test/retest variability was calculated as the absolute difference of test minus retest divided by the mean of test/retest and expressed as a percent. In addition, the reproducibility of left and right striatal asymmetry and putamen:caudate ratios were determined. RESULTS: The two outcome measures demonstrated excellent test/retest reproducibility for both the Parkinson's disease and healthy subject groups with variability of striatal V3" = 16.8 +/- 13.3% and percent striatal uptake = 6.8 +/- 3.4% for Parkinson's disease patients and V3" = 12.8 +/- 8.9% and %SSU = 7.0 +/- 3.9% for control subjects. There were no statistically significant differences in test/retest variability between control subjects and Parkinson's disease patients for either outcome measure. The reproducibility of left/right asymmetry indices and putamen-to-caudate ratios showed no patient versus control subject differences. The asymmetry index had greater test/retest variability than the other outcome measures. CONCLUSION: These data suggest that SPECT imaging performed at 24 hr postinjection of [123I]beta-CIT permits calculation of reliable and reproducible measures of dopamine transporters in both Parkinson's disease patients and control subjects and supports the feasibility of using [123I]beta-CIT in the evaluation of disease progression in Parkinson's disease.     

The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance

L-dopa, the major treatment for Parkinson's disease (PD), depletes S-adenosyl-L-methionine (SAM). Since SAM causes PD-like symptoms in rodents, the decreased efficacy of chronic L-dopa administered to PD patients may result from a rebound increase in SAM via methionine adenosyl transferase (MAT), which produces SAM from methionine and ATP. This was tested by administering intraperitoneally saline, or L-dopa to mice and assaying for brain MAT activity. As compared to controls, L-dopa (100 mg/kg) treatments of 1 and 2 times per day for 4 days did not significantly increase MAT activity. However, treatments of 3 times per day for 4 and 8 days did significantly increase the activity of MAT by 21.38% and 28.37%, respectively. These results show that short interval, chronic L-dopa treatments significantly increases MAT activity, which increases the production of SAM. SAM may physiologically antagonize the effects of L-dopa and biochemically decrease the concentrations of L-dopa and dopamine. Thus, an increase in MAT may be related to the decreased efficacy of chronic L-dopa therapy in PD.     

Speech disorders in Parkinson patients

Parkinson's disease is not only a disorder affecting locomotion, but often also causes speech problems. Functional impairment of articulation, phonation, prosody and also respiration may occur. Speech disorder is frequent in Parkinson's disease and often has an impact on the quality of life. Speech therapy is by no means offered as a matter of course to these patients. This article outlines the different approaches of speech therapy regarding respiration, loudness, articulation, prosody, and intonation. Speech therapy seems to be useful in patients with Parkinson's disease only if there is no cognitive impairment; success also depends on motivation and eventual frequent repetition of therapy series.