Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate relationships between cognition and regional brain function, we studied 20 non-demented patients with idiopathic Parkinson's disease (PD), 21 mildly demented patients with Alzheimer's disease (AD) and 24 control subjects using cognitive testing and single photon emission computerized tomographic (SPECT) measurements of relative regional cerebral blood flow (rCBF). Neuropsychological tests were grouped into clusters reflecting frontal lobe executive abilities, perseveration, memory and visuospatial ability, with a summary score summarizing performance in all four of these spheres. SPECT imaging utilized the tracer [123I]N-isopropyl-p-iodoamphetamine with a relative measure of regional tracer uptake normalized to occipital radiotracer uptake (rCBF ratios). Patients with PD performed more poorly than controls in all cognitive domains, and were intermediate to AD patients and controls in tests of memory and overall cognitive functioning. Those PD patients who performed most poorly on neuropsychological testing showed lowest rCBF ratios in left and right temporal lobes. Using a stepwise multiple regression procedure, we examined patterns of correlations between cognitive clusters and predictor variables, including rCBF ratios, in the PD patients. We found that while patient age was a strong determinant of performance on the memory cluster and the summary score, dorsolateral frontal lobe perfusion and scores on a depression inventory accounted for a greater proportion of the variance of the frontal lobe and perseveration clusters than did age. These results imply that different neural mechanisms are responsible for the different aspects of cognitive decline seen in PD patients, with overall cognitive function closely related to age and temporal perfusion, while frontal lobe abilities are more linked to frontal perfusion and the presence of depression.
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PMID:Cognitive function and regional cerebral blood flow in Parkinson's disease. 160 80

Irreversible and unspecific inhibitors of MAO were the first modern antidepressants, but after an initial success they fell into discredit due to adverse side effects. In the past two decades interest in MAO inhibitors has been renewed because of progress in basic research, a milestone being the finding that there are two subtypes of MAO, MAO-A and MAO-B. These are distinct proteins with high amino acid homology, coded by separate genes both located on the short arm of the human chromosome X. The enzyme subforms show different substrate specificities in vitro and different distributions within the central nervous system and in peripheral organs. In the central nervous system of man MAO-A seems to be mainly involved in the metabolism of 5 HT and noradrenaline, whereas 2-phenylethylamine and probably dopamine are predominantly deaminated by MAO-B. In the intestinal tract tyramine is mainly metabolized by MAO-A. These characteristics indicate distinct physiological functions of the two MAO-subforms. Several irreversible and reversible non-hydrazine inhibitors with relative selectivities for one of the MAO-subforms have been developed. They belong to various chemical classes with different modes of enzyme inhibition. These range from covalent mechanism based interaction (e.g. by propargyl- and allylamine derivatives) to pseudosubstrate inhibition (e.g. by 2-aminoethyl-carboxamides) and non-covalent interaction (e.g. by brofaromine, toloxatone and possibly moclobemide). The most important pharmacological effects of the new types of MAO inhibitors are those observed in neuropsychiatric disorders. The inhibitors of MAO-A show a favorable action in various forms of mental depression. The drugs seem to have about the same activity as other types of antidepressants, including tricyclic and related compounds as well as classical MAO inhibitors. The onset of action of the MAO-A inhibitors is claimed to be relatively fast. Other possible indications of these drugs include disorders with cognitive impairment, e.g. dementia of the Alzheimer type. In subjects with Parkinson's disease the MAO-B inhibitor L-deprenyl exerts a L-dopa-sparing effect, prolongs L-dopa action and seems to have a favorable influence regarding on-off disabilities. The action is in general transitory (months to several years). In addition L-deprenyl has been shown to delay the necessity for L-dopa treatment in patients with early parkinsonism. Whether the drug influence the progression of the disease is still a matter of debate. L-deprenyl also appears to have some antidepressant effect (especially in higher doses) and to exert a beneficial influence in other disorders, e.g. dementia of the Alzheimer type.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The new generation of monoamine oxidase inhibitors. 160 14

Slices of human neocortex prelabelled with [3H]choline were superfused and stimulated electrically (3 Hz, 2 ms, 24 mA) in order to investigate the autoreceptor-mediated modulation of acetylcholine (ACh) release. The concentration-response curve of the muscarinic agonist oxotremorine (pKd = 6.76 +/- 0.06), which was equipotent to ACh, was shifted to the right in a parallel manner by atropine (pA2 = 8.56 +/- 0.11), as evaluated by non-linear regression analysis. Calculation of the biophase concentration of ACh showed that no ACh could be assumed to be present under these conditions, whereas following inhibition of the acetylcholinesterase by physostigmine (0.1 microM) a biophase concentration of 10(-6.89 +/- 0.11) M was estimated. The depression of ACh release due to physostigmine and tacrine, another anticholinesterase, was antagonized by atropine. When the autoinhibition was operative atropine and the M2 subtype specific muscarinic antagonists, AF-DX 116 and methoctramine, significantly increased the release of ACh whereas the 'facilitatory' effects of the M1 and M3-specific drugs, pirenzepine and hexahydrosiladifenidol, were not significant. Although different disinhibitory effects of the subtype-specific antagonists were found, they did, however, not show a pattern which would allow a clear characterisation of the subtype of muscarinic receptor associated with the autoreceptor. The release of ACh from neocortex tissue of the (non-demented) neurosurgical patients decreased with their age. This finding is consistent with the hypothesis that the normal aging process resembles a delayed and attenuated disease process of senile dementia of Alzheimer's type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The autoinhibitory feedback control of acetylcholine release in human neocortex tissue. 161 39

This article reviews the empirical literature available on the phenomenon of depression in Alzheimer's disease (AD). Although not extensively studied, there is accumulating evidence to suggest that depression affects a large number of patients with AD and can have profound effects on both the long-term functioning of these patients and the well-being of their caregivers. Thus far, the field is dominated by studies of prevalence. Considerably rarer are studies investigating etiology, association with other aspects of disease, impact on patients and caregivers, assessment, and treatment. The conceptual issues, methodological differences, and implications of the studies that exist thus far are discussed.
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PMID:Alzheimer's disease and depression. 161 92

The relationship between depression and dementia in Parkinson's disease (PD) has rarely been explored. Using a quantitative EEG (qEEG) parameter, we studied four groups of subjects: PD, demented Alzheimer's type and major depressed patients and normal controls. The qEEG data were compared with those of the Mini-Mental State and the Hamilton Depression Scale. The qEEG pattern was different in the four groups of subjects. Moreover, there was a significant correlation between the qEEG data and the other variables, and, particularly, with the cognitive performances. Our findings demonstrate that the qEEG method of assessment may give valuable data for a better classification of dementia syndromes and for a distinction between dementia and pseudodementia.
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PMID:Quantitative electroencephalography in Parkinson's disease, dementia, depression and normal aging. 162 76

Previous studies have shown that general practitioners often fail to detect dementia and depression in their elderly patients. The present study aimed to find out how much knowledge general practitioners have of these disorders. The knowledge of 36 general practitioners was assessed and it was found that they had a limited knowledge of the symptoms and signs of dementia and depression. Furthermore, almost 60% of the general practitioners did not know that Alzheimer's disease is the most common dementing disorder.
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PMID:General practitioners' reported knowledge about depression and dementia in elderly patients. 164 7

We investigated quantitative EEG brain mapping as a physiologic marker of drug response while studying the stability of intersubject variability in patients with Alzheimer's disease (AD) who were receiving bethanechol through intracerebroventricular (ICV) shunts. Two of the patients had previously demonstrated cognitive and behavioral improvements on medication; the third had cognitive deterioration complicated by agitated depression. All three patients were reexamined in a dose-response paradigm. Serial brain mapping examinations were performed along with brief cognitive testing. All patients showed drug responses that were comparable with responses during their initial dose-response phase. There were strong linear correlations between global decreases in 2 to 6 Hz slow-wave activity and cognitive improvement. Brain mapping demonstrated that slowing decreased in magnitude and field with increasing dose until optimal dose was reached; with supra-optimal doses, the magnitude and field of the slowing increased dramatically. These results suggest that the quality of cholinomimetic drug responses are stable over time in individual patients, and that magnitude and pattern of slow-wave activity as measured by brain mapping may be useful in monitoring treatment with cholinomimetic agents.
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PMID:Stable bimodal response to cholinomimetic drugs in Alzheimer's disease. Brain mapping correlates. 167 88

A long-lasting potentiation (usually following an initial short depression) of neuronal evoked responses was induced in neurons of rat sensorimotor cortex after a single application of the muscarinic agonists, oxotremorine, McN-A-343, or oxotremorine-M. The potentiation was characterized as being of slow onset (several minutes), progressive development, long-lasting (for as long as two hours), and was evident for both glutamate- and acetylcholine-evoked neuronal discharges. Potentiation was manifested as an increase in the frequency and duration of the evoked neuronal discharges, in a dose-dependent fashion. Blockade could be achieved if a muscarinic antagonist (atropine, pirenzepine or gallamine) was applied prior to, but not after, development of the long-lasting potentiation. These results suggest that certain muscarinic agonists may be useful in reducing the memory deficits of patients with Alzheimer's disease.
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PMID:Muscarinic agonist-mediated induction of long-term potentiation in rat cerebral cortex. 168 May 27

Patients with Alzheimer's disease (AD) have been reported to have a rate of nonsuppression on the dexamethasone suppression test (DST) comparable to that of patients with major depression. With symptoms of depression being increasingly recognized in patients with AD, studying their DST response may provide clues to the etiology of the abnormal response in both diagnostic groups. A correlation between dementia severity and post-dexamethasone cortisol was found within the group of male, but not female AD patients. Within the group of elderly depressives, a correlation between post-dexamethasone cortisol and ratings of depression was found. Serum dexamethasone levels were not significantly lower in the nonsuppressors as compared with suppressors in either diagnostic group. Within the AD group, dexamethasone levels themselves correlated significantly with ratings of dementia severity and with the Wechsler Memory Scale score. Cerebrospinal fluid (CSF) 3-methoxy-4-hydroxyphenylglycol (MHPG) correlated positively with 4:00 pm post-dexamethasone cortisol level and with ratings of dementia severity in the AD patients. Findings are discussed in light of the known clinical and other biological similarities between AD and major depression, followed by a review of theories regarding the etiology of the hypothalamic-pituitary-adrenal abnormalities in these two illnesses.
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PMID:The dexamethasone suppression test in Alzheimer's disease and major depression: relationship to dementia severity, depression, and CSF monoamines. 171 99

Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients (n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, and HVA levels were not significantly different among diagnostic groups. Within a group of "depressed" AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression.
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PMID:CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression. 171 76


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