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)

The diagnosis of Alzheimer's disease (AD) was verified at post-mortem examination in 46 patients (9 male: 37 female; mean age 83.6 +/- 6.5 years) from a prospective clinical study. Compared to 10 age-matched controls, the total AD group showed a significant neuronal loss in the locus coeruleus, dorsal raphe nucleus, substantia nigra and in the basal nucleus of Meynert. Twelve patients (1 male: 11 female) had experienced symptoms of depression. These patients had significantly lower neuronal counts in the locus coeruleus, but less severe cell loss in the basal nucleus of Meynert compared to the AD patients without depression.
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PMID:[Organic correlates of depressive symptoms in Alzheimer's dementia. Results of a prospective study, review of the literature]. 140 28

Positron emission tomography (PET) is the only method that measures concomitantly in the same cerebral region the main haemodynamic (blood flow, blood volume) and metabolic (oxygen and glucose consumption) parameters, thereby providing essential data concerning the supply of substrates by circulation and their principally neuronal/synaptic use by the cells. In "healthy" (i.e. normal) ageing, there is a progressive decrease of oxygen and glucose consumption--with subsequent reduction of cerebral blood flow (CBF)--which predominates in the neocortex and suggests a dysfunction of neuronal circuits perhaps responsible for some age-related changes in cognitive functions. The metabolic depression in the neocortex seems to be accentuated during the more "common" ageing which may include cerebrovascular risk factors, lesions of the white matter in varying numbers and/or degradation of cognitive functions. Strategically located brain lesions of vascular origin (e.g. damaging of the thalamic nuclei), may produce a thalamo-cortical disconnection which induces a diffuse cortical hypometabolism associated with severe cognitive disorders. In degenerative dementias (particularly Alzheimer's disease), which include cortical and subcortical neuronal lesions (e.g. those involving the cholinergic system), there is a hypometabolism preferentially affecting the associative cortex. The cumulative effects on cortical functioning of multiple vascular lesions, superimposed on degenerative neuron loss, might account for age-related cognitive disorders in "normal" ageing as well as in the so-called "vascular" or "mixed" dementias.
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PMID:[Cerebral and cardiovascular aging and brain energy metabolism. Studies with positron-emission tomography in man]. 140 78

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.
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PMID:Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. 142 88

This study describes the prevalence of violence and the putative risk factors for violence in 184 Alzheimer patients and their primary caregivers living in the community. Analysis of the severe violence subscale of the Conflict Tactics Scale indicated that 15.8% of patients had been violent in the year since diagnosis. A total of 5.4% of caregivers reported being violent toward the patient. The overall prevalence of violence was 17.4%. The variables most associated with violence were caregiver depression and living arrangement.
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PMID:Severe family violence and Alzheimer's disease: prevalence and risk factors. 142 52

This paper views conflict in Alzheimer's caregiving families as a multidimensional construct. Three conceptually distinct dimensions of family conflict are described and examined in relation to depression and anger. Regression analyses indicate that conflicts involving family members' attitudes and actions toward the caregiver are associated with increased risk for depression among caregivers, whereas conflicts stemming from family members' attitudes and behaviors toward the patient are most likely to result in anger. Self-concepts and normative expectations are implicated as key explanatory variables.
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PMID:Conflict in Alzheimer's caregiving families: its dimensions and consequences. 142 77

In two inter-Nordic multicenter controlled studies the effect of Citalopram on elderly patients with depression and emotional disturbances has been studied. One investigation included 98 patients in whom Alzheimer type dementia (AD/SDAT) and vascular dementia (VD) had been diagnosed, many of whom also had emotional disturbances. After four weeks treatment with Citalopram (10-30 mg/daily) there was significant improvement in confusion, irritability, anxiety, depressed mood and restlessness. No effect was seen on the intellectual capacity or motor performance measured. In the other study, which was a six weeks trial comparing Citalopram and placebo, elderly patients with a treatment-requiring depression were treated. Demented as well as non-demented patients were included. The Hamilton Depression Scale, the Montgomery-Asberg Depression Rating Scale and The Clinical Global Impressions all recorded an effect of Citalopram superior to that of placebo. In both studies depressive symptoms as well as symptoms of agitation, anxiety, restlessness and irritability improved. Citalopram is therefore considered not only an antidepressive drug but also an emotional stabilizer. The drug was well tolerated by elderly often somatically ill patients. Side effects were few.
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PMID:Treatment of depression in elderly patients with and without dementia disorders. 143 Oct 23

Occupational therapists treating older people with Alzheimer disease know that they must also consider the others who are affected by the disease, the informal caregivers. Intervention is most effective when it enables both the impaired person and the primary caregiver to manage the secondary symptoms of dementia. Unfortunately, little is understood about how caregivers approach and carry out their tasks and about why male and female caregivers respond differently to their caregiving role in terms of depression, burden, stress, and substance abuse. This paper discusses the effects of gender on dementia management plans of spousal caregivers. Husbands and wives have different approaches to caregiving; each approach has consequences. Male caregivers adopt a task-oriented approach to their duties and carry out their activities in a linear fashion; female caregivers use a parent-child approach and nest activities inside one another in a constant stream of work. Two cases are presented to illustrate gender differences in dementia management plans. Implications for occupational therapy include suggestions for supporting men and women in their caregiving role, modulating the negative consequences of caregiving, and conducting research to demonstrate the efficacy of an occupational therapy approach.
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PMID:Gender differences in dementia management plans of spousal caregivers: implications for occupational therapy. 146 72

Early referral for specialist assessment is becoming more common with memory disorders and dementia: the mean Mini-Mental State Examination (MMSE) score of new patients at our clinic rose from 18.7 to 20.7 between 1986 and 1990. The clinical diagnosis of mild to moderate dementia has been recognized to be difficult, but several studies have reported cross-sectional diagnosis. We examined the number of visits required to establish a clinical diagnosis of dementia in the first 125 patients attending a Memory Disorders Clinic who had at least two visits (six months apart) and the stability of the diagnoses. Just under half of the patients required at least two visits to establish the clinical diagnosis. The MMSE was not a good guide to the number of visits required but the diagnosis at the first visit remained stable in all patients who scored < or = 10/30. Sixteen per cent of patients interchanged between the categories of Alzheimer's, mixed and vascular dementias. Possible age-associated memory impairment progressed to dementia in six of eight cases, and depression to dementia in three cases. The diagnosis of mild to moderate dementia should not be restricted to a cross-sectional approach, but should involve serial clinical, psychological and affective assessments.
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PMID:Longitudinal diagnosis of memory disorders. 147 75

The subcortical dysfunction hypothesis of verbal learning and memory deficits in depression was evaluated by comparing the memory test profiles of unipolar depressives (n = 40) and bipolar depressives (n = 9) with those of patients with a prototypical subcortical dementia (Huntington's disease, HD), patients with a prototypical cortical dementia (Alzheimer's disease, AD), and normal controls. In a discriminant function analysis that well-differentiated the HD, AD, and normal subjects, it was found that 28.6% of the depressed patients were classified as HD patients (DEP-HD subjects), 49.0% were classified as normals (DEP-N subjects), none were classified as AD patients, and 22.4% were not well-classified. The DEP-HD group closely resembled the HD group on additional indices of verbal learning and memory, and differed from the DEP-N group, which strongly resembled the normal control group. DEP-N patients also performed significantly better than DEP-HD patients on a number of other neuropsychological tests (e.g., WAIS-R Digit Symbol, category fluency, Trail Making Test Part B). The findings provide support for the subcortical dysfunction hypothesis, but only for a subgroup of depressed patients. Implications for differentiating depressive "pseudodementia" from AD are discussed.
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PMID:The subcortical dysfunction hypothesis of memory deficits in depression: neuropsychological validation in a subgroup of patients. 147 39

Alterations in calcium transport appear to be functionally significant. Treatment with drugs that promote calcium uptake partially reverse some of the age-related deficits in calcium-dependent processes. Thus, the relevance of decreased calcium coupled receptor binding is supported by the ability of 3,4-diaminopyridine to promote acetylcholine release by forebrain slices from aged mice. This drug also reduces the age-related depression in synaptosomal calcium uptake in aged rats and mice. 3,4-Diaminopyridine also reverses the age-related deficit in calcium transport, the age-related deficits in the tight rope test, and 8 arm maze performance. 3,4-Diaminopyridine is also effective in nonexcitable tissues, such as cultured skin fibroblasts; it increases the decreased cytosolic-free calcium. Depressed cell spreading of fibroblasts can be reversed by treatment of cells with the calcium ionophore A23187 which promotes calcium influx. 4-Aminopyridine, a similarly related compound, partially reverses short-term memory deficits in patients with Alzheimer's disease. Tetrahydroaminoacridine, an aminopyridine analog with anticholinesterase properties, produces clinical improvement in behavioral deficits due to Alzheimer's disease. Only recently has the aging brain become a subject of intense study. Evidently, the neurobiology of aging needs to develop its own theories to account for the unique aspects of brain aging as well as integrate them with the peripheral changes. An exciting but unexplored area of research in the aging brain concerns the coupling between calcium and the final end product, the induction of genes. Still unknown are the molecular events that set these processes in motion. In addition, whether conditions such as dietary restriction that increase longevity in certain rodents also retard age-related changes in calcium remains to be determined.
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PMID:Changes in calcium's role as a messenger during aging in neuronal and nonneuronal cells. 148 59


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