The locus ceruleus and dementia in Parkinson's disease

We compared numbers of neuronal profiles in the locus ceruleus (LC) from sections of brainstem in 13 patients with Parkinson's disease (PD) without concurrent Alzheimer's disease (AD) with counts from age-matched controls and from patients with PD and concurrent AD. We also evaluated the relationships between presence of dementia or LC neuronal loss and additional pathologic measures related to dementia in PD. Among patients with PD without concurrent AD, the presence of dementia was associated with significantly lower LC neuronal counts (at all anatomic levels); greater neuronal loss within the ventral tegmental area, nucleus basalis of Meynert, and possibly the medial (but not the lateral) substantia nigra pars compacta; and more Lewy bodies in the anterior cingulate gyrus. Correlations between lower LC neuronal counts and these other pathologic measures were generally positive and often significant. We conclude that dementia in PD is associated with pathologic involvement of multiple extranigral neuronal populations.     

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.     

Component analysis of a rhythmic finger tapping task in individuals with senile dementia of the Alzheimer type and in individuals with Parkinson's disease.

The present experiment examined different components of motor control that may be impaired in normal aging, senile dementia of the Alzheimer type (SDAT), and Parkinson's disease (PD). Specifically, A. M. Wing and A. B. Kristofferson's (1973) formal quantitative model of rhythmic finger tapping was used to obtain estimates of central timekeeping and response execution components of timing control. Ss included young college students, healthy older adults, nondemented individuals with PD. and individuals with very mild and mild SDAT. Individuals with mild SDAT exhibited a breakdown in the central timekeeping mechanism but not in the execution of the response. Both very mild SDAT and PD individuals did not show any deficits in the 2 timing mechanisms relative to age-matched healthy controls. Finally, there was no effect of normal aging on timing control in this task. This study underscores the importance of examining issues of motor control in SDAT as a function of separate processing components and stages of disease progression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynorphin agonist therapy of Parkinson's disease

Striatal dynorphin system function may be altered in Parkinson's disease. To evaluate whether treatment with a selective dynorphin agonist improves motor symptoms, four parkinsonian patients received single daily injections of spiradoline under controlled conditions. Doses ranging from 1 to 4 micrograms/kg had no discernible effect on motor performance when given alone or in combination with levodopa-carbidopa. Three patients developed dose-limiting adverse effects, especially behavioral alterations. These results suggest that dynorphin replacement strategies, using spiradoline-like kappa-1 agonists, may have limited value in the therapy of patients with Parkinson's disease.     

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)     

High prevalence of vitamin D deficiency and reduced bone mass in Parkinson's disease

Despite excessive hip fractures in patients with Parkinson's disease (PD), little is known about bone changes in these patients. We measured bone mineral density (BMD; Z scores) in PD patients and analyzed its relation to serum biochemical indices and sunlight exposure. We measured BMD in 71 patients in the second metacarpals and divided the patients into two groups according to functional independence; group 1, Hoehn and Yahr stages 1 and 2; and group 2, stages 3 to 5. In four of 20 patients in group 1 (20%), the Z score was less than -1.0, indicating osteopenia. In 51 patients in group 2, 31 (61%) had a Z score less than -1.0. The group 1 patients showed a normal mean serum level of 25-hydroxyvitamin D (25-OHD; 21.7 ng/ml), while most group 2 patients were in a deficiency range (group mean 8.9 ng/ml). Many group 2 patients were sunlight deprived. Both groups had elevated serum ionized calcium levels correlating positively with Hoehn and Yahr stage and markedly depressed serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations, indicating that immobilization-induced hypercalcemia had inhibited 1,25-[OH]2D production. Z scores correlated positively with 25-OHD levels and negatively with parathyroid hormone concentration and Hoehn and Yahr stage. Vitamin D deficiency due to sunlight deprivation and hypercalcemia induces compensatory hyperparathyroidism, which contributes to reduced BMD in PD patients, particularly those who are functionally dependent. Low BMD increases risk of hip fractures in patients with PD but may be improved by vitamin D supplementation.     

A scientific rationale for protective therapy in Parkinson's disease

The desire to introduce neuroprotective therapy for Parkinson's disease has begun to focus attention on pathogenetic mechanisms responsible for cell death. Considerable theory and some evidence have now accumulated to suggest that factors related to oxidative stress, mitochondrial bioenergetic defects, excitatory neurotoxicity, calcium cytotoxicity, and trophic factor deficiencies acting either singularly or in combination may contribute to the development of cell death in Parkinson's disease. A better understanding of the specific pathogenetic mechanism involved in cell degeneration might provide a scientific basis for testing a putative neuroprotective therapy. This chapter reviews the theory and evidence in support of these different mechanisms and possible strategies that might provide neuroprotection and interfere with the natural progression of Parkinson's disease.     

Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Parkinson's disease

We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 34 patients with Parkinson's disease (PD) and 47 controls. CSF and serum vitamin E levels were correlate. The mean CSF and serum vitamin E levels, and the CSF/serum ratio of PD patients did not differ significantly between the groups. There was no influence of antiparkinsonian therapy on CSF vitamin E levels. CSF vitamin E levels did not correlate with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. These results suggest that CSF vitamin E concentrations are unrelated with the risk for PD.     

Parkinson's dementia and Alzheimer's dementia: an evoked potential comparison

Auditory endogenous event-related potentials (ERPs) and flash visual evoked potentials (VEPs) were recorded in 26 elderly patients with idiopathic Parkinson's disease (PD), 14 with dementia and 12 non-demented, 16 elderly patients with Alzheimer dementia (AD) and 15 cognitively intact controls. ERP P3 and flash-VEP N2, P2 and delta (P2-P1) latency measures were significantly increased in the demented PD group compared with controls. The ERP P3 latency was also significantly delayed in the AD group compared with controls, but the differences in the flash-VEP measures from controls were not significant. No significant differences were noted between the PD groups, except for a significantly shorter flash-VEP N1 latency in the demented PD group; this was also the only significant evoked potential difference between the AD and PD dementia groups, which were otherwise electrophysiologically similar.     

Long-term cued recall of tasks in senile dementia.

Participants with senile dementia of the Alzheimer's type, vascular dementia, or both, associated a task with a cue. On reinstatement of the cue 1 day later, a substantial portion of the sample recalled the task. The teaching method, both with and without participant performance of the task (PPT), was spaced retrieval with supplementary or fading cues provided as required. Findings were that (a) PPT encoding and retrieval encoding, separately, assisted later recall; (b) retrieval combined with PPT encoding increased the probability of task performance at final recall; (c) repetition in the absence of retrieval or PPT was less effective; and (d) there was no forgetting between 1 hr and 1 day. Theoretical and clinical aspects of these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation between diffuse EEG abnormalities and cerebral atrophy in senile dementia

Thirty-five elderly patients were investigated because of clinical signs of dementia. The presence or diffuse cerebral atrophy, and its severity, were determined by the use of computed tomography (CT scan). All of the patients were also examined by electroencephalography (EEG), and the presence of diffuse abnormalities, especially diffuse slowing, was noted. Specifically, patients with normal or near-normal EEGs were compared with those with severe diffuse slowing. No correlation between the presence or severity of diffuse EEG abnormalities and the degree of cerebral atrophy as measured by CT scan was found. Though the EEG is clearly identifying physiological dysfunction of nerve cells in demented patients it does not appear to be reliable tool for the prediction of diffuse cerebral atrophy in this population.     

Neuropsychologic method in diagnosis of mild dementia in elderly and senile patients

Clinical neuropsychologic investigation was performed in 95 patients of elderly and senile age with mild dementia: 20 individuals with Alzheimer's disease (AD), 25 patients with senile dementia of Alzheimer's type (SDAT), 25 patients with vascular dementia (VD) and 25 patients with combined dementia of vascular and Alzheimer's types (DAT/VD). Clinical diagnosis of mild dementia was performed according to ICD-10. Neuropsychologic study was based on the theory and method of A.R. Luria. Syndrome of disorder of high psychic functions (HPF) in patients with mild SDAT was characterised by pathology of frontal cerebral structures and by significantly less defects of profound cerebral structures. According to the examination results the group of patients with mild AD was divided into 2 subgroups: 1) patients in which syndrome of HPF disorders was determined by pathology of parietal-temporal and profound cerebral structures and 2) patients with dysfunction of profound and frontal cerebral structures. Symptoms associated with profound cerebral structures were the main ones in patients with mild VD. Syndrome of HPF disorder included in mild DAT/VD symptoms connected with subcortical and profound brain structures as well as with frontal structures too. Besides, there were also defects in posterior frontal and parietal structures of the brain.