RESUMO
The Mini-Mental State exam is a widely used screening instrument for dementia. Recent research has suggested that errors in classification reported for this instrument may be due to premorbid levels of intelligence and education, Thirty-one ambulatory patients diagnosed with Alzheimer's disease were administered a standard neuropsychological testing battery. MMSE scores and intelligence are significantly correlated. However when memory ability is partialed out, the covariance of MMSE and intellectual abilities does not add any further information to that already provided by the memory scores.
Assuntos
Doença de Alzheimer/classificação , Programas de Rastreamento/métodos , Transtornos da Memória/classificação , Entrevista Psiquiátrica Padronizada/normas , Escalas de Wechsler/normas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Masculino , Programas de Rastreamento/normas , Transtornos da Memória/complicações , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
Low, micromolar concentrations of aluminum (in the presence of NaF) were shown to strongly activate human platelet adenylate cyclase and provided a useful probe for evaluating cyclic AMP second messenger function distal to the receptor: The effect of normal aging and disease state on second messenger activity in man was studied by measurements of the aluminum-activated enzyme. A significant decline in aluminum-stimulated platelet adenylate cyclase activity in older, healthy subjects was observed. An age-associated decline in NaF-stimulated cyclic AMP synthesis was also demonstrated for normal, non-demented subjects. These findings suggest an age-associated lesion at the level of the guanine nucleotide regulatory protein/catalytic subunit of the adenylate cyclase complex. However, for patients with Alzheimer's disease no such decline in platelet adenylate cyclase activity was detected, and increased sensitivity to both aluminum and NaF was demonstrated.
Assuntos
Adenilil Ciclases/metabolismo , Envelhecimento , Alumínio/farmacologia , Doença de Alzheimer/enzimologia , Plaquetas/enzimologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The intracellular effects of a number of hormonal signals are mediated by the cyclic AMP second messenger system in man and the ubiquitous distribution of hormone-stimulated adenylate cyclase suggests the importance of this enzyme complex in normal aging and pathophysiological states. Various vectors including heredity, endogenous catecholamines, steroid hormones, and drugs affect the activity of hormone-stimulated adenylate cyclase in man. The effect of heredity was studied using lymphocytes obtained from monozygotic twin pairs and age and sex-matched sib pairs. Only for forskolin-stimulated activity is a significant proportion of individual variance attributable to heredity, suggesting the relative stability of the catalytic subunit. Beta-adrenergic and prostaglandin E-1 activity are "state" characteristics and their activities are controlled by environmental parameters. A significant reduction in isoproterenol-stimulated cyclic AMP accumulation between the menses and luteal phase of the menstrual cycle is observed in lymphocytes obtained from 11 female subjects. The lowest level of beta-adrenergic receptor activity is associated with the highest levels of progesterone and estradiol hormone levels in blood. Lithium at therapeutic concentrations markedly inhibits adenylate cyclase activity in platelet membranes. Moreover, marked individual differences are observed in sensitivity to lithium as determined by Dixon plot derived Ki values for 9 normal, healthy subjects. Human adenylate cyclase obtained from platelets and lymphocytes is activated by micromolar amounts of aluminum in the presence of NaF. Irreversible activation of adenylate cyclase by aluminum is suggested as a possible mechanism of this metal's neurotoxicity. The biochemical basis for the age-associated decline in beta-adrenergic responsiveness in man is discussed. Several investigations suggest a deficit at two levels in the adenylate cyclase complex: an impaired coupling of the receptor/N protein subunits and an additional lesion distal to the receptor at the level of N/C coupling. Perfusion studies with salbutamol suggest that the decline in beta-adrenergic sensitivity is general and not restricted to lymphocytes. Possible abnormalities in cyclic AMP signal amplification and recognition in various disease states is discussed. Increased prostaglandin E-1-stimulated cyclic AMP accumulation is observed in lymphocytes obtained from patients with Alzheimer's disease compared to age-matched controls and correlated with severity of the disease state.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Envelhecimento , Alumínio/toxicidade , AMP Cíclico/fisiologia , Hormônios/fisiologia , Adenilil Ciclases/análise , Doença de Alzheimer/etiologia , Feminino , Genética , Homeostase , Humanos , Lítio/farmacologia , Linfócitos/enzimologia , Masculino , Receptores Adrenérgicos beta/efeitos dos fármacosRESUMO
The effect of prior incubation with a single concentration of isoproterenol (10(-4) M) for 2 hours at 37 degrees C on isoproterenol-stimulated cyclic AMP accumulation in intact lymphocytes from young, old and subjects with Alzheimer's disease was studied. In lymphocytes from all three subjects groups prior incubation of cells with isoproterenol resulted in a significant reduction of cyclic AMP accumulation upon subsequent stimulation with isoproterenol.
Assuntos
Adenilil Ciclases/sangue , Envelhecimento , Doença de Alzheimer/enzimologia , Linfócitos/enzimologia , Receptores Adrenérgicos beta/sangue , Adulto , Idoso , AMP Cíclico/sangue , Feminino , Humanos , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , Prostaglandinas E/sangueRESUMO
Reduced lymphocyte beta-adrenergic receptor activity was observed in patients with Alzheimer's disease and in aged controls; a parallel decline in lymphocytic prostaglandin E1 receptor activity was seen in the aged controls. In the Alzheimer patients, however, such lymphocytic prostaglandin E1 receptor activity was significantly raised and correlated with a rating scale for severity of dementia.