RESUMEN
BACKGROUND: Preclinical Alzheimer's disease (AD) provides an opportunity for the study and implementation of interventions and strategies aimed at delaying, mitigating, and preventing AD. While this preclinical state is an ideal target, it is difficult to identify efficiently and cost-effectively. Recent findings have suggested that cognitive-motor dual task paradigms may provide additional inference. OBJECTIVES: Investigate the relationship between dual task performance and amyloidosis, suggestive of preclinical Alzheimer's disease and whether dual task performance provides additional information beyond a cognitive composite, to help in the identification of amyloidosis. DESIGN: Cross-sectional. SETTING: Outpatient specialty brain health clinical research institution in the United States. PARTICIPANTS: 52 cognitively healthy adults. MEASUREMENTS: The data included demographics, amyloid standardized uptake value ratio obtained via florbetapir-PET, neuropsychological testing, apolipoprotien E genotype, and dual task performance measures. Data were analyzed via hierarchal multiple linear regression or logistic regression, controlling for age, education, and apolipoprotien E genotype. Receiver operating characteristic curves were plotted, and sensitivity and specificity calculated via 2x2 contingency tables. RESULTS: There was a moderate relationship (rs>.30) between motor and cognitive dual task effects and amyloid standardized uptake value ratio (ps<.042). A strong relationship (r=.58) was found between combined dual task effect, a measure of automaticity derived from dual task performance, and amyloid standardized uptake value ratio (p<.001). Additionally, combined dual task effect showed promise in its unique contributions to amyloid standardized uptake value ratio, accounting for 7.8% of amyloid standardized uptake value ratio variance beyond cognitive composite scores (p=.018). Additionally, when incorporated into the cognitive composite, combined dual task effect resulted in improved diagnostic accuracy for determining elevated amyloid standardized uptake value ratio, and increased the sensitivity and specificity of the cognitive composite. CONCLUSSION: Dual task performance using the combined dual task effect, a measure of automaticity, was a moderate predictor of cerebral amyloidosis, which suggests that it has utility in the screening and diagnosis of individuals for preclinical AD. Additionally, when combined with the cognitive composite, the combined dual task effect improves diagnostic accuracy. Further research is warranted.
Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Adulto , Enfermedad de Alzheimer/diagnóstico por imagen , Amiloide , Péptidos beta-Amiloides , Amiloidosis/diagnóstico por imagen , Estudios Transversales , Humanos , Tomografía de Emisión de Positrones , Análisis y Desempeño de TareasRESUMEN
Galanin-overexpressing transgenic mice (GAL-tg) generated on a dopamine beta-hydroxylase promoter were previously shown to express high levels of galanin mRNA in the locus coeruleus, and to perform poorly on challenging cognitive tasks. The present study employed radioimmunoassay to quantitate the level of galanin peptide overexpression in two brain regions relevant to learning and memory, the hippocampus and cerebral cortex. Approximately 4-fold higher levels of galanin were detected in the hippocampus of GAL-tg as compared to WT. Approximately 10-fold higher levels of galanin were detected in the frontal cortex of GAL-tg as compared to WT. A second cohort of GAL-tg and WT again showed high levels of galanin overexpression in GAL-tg as compared to WT in both brain regions. Correlation analyses were conducted between galanin peptide concentrations and behavioral scores on four learning and memory tasks: the Morris water maze, social transmission of food preference, standard delay fear conditioning, and trace fear conditioning. While some significant correlations were detected, neither hippocampal nor cortical galanin levels in the two cohorts of GAL-tg consistently correlated with performance across these diverse cognitive tasks. Several interpretations of these findings are discussed, including the possibility that a threshold level of galanin overexpression is sufficient to impair performance on learning and memory tasks in mice.
Asunto(s)
Corteza Cerebral/fisiología , Cognición/fisiología , Galanina/genética , Hipocampo/fisiología , Animales , Condicionamiento Psicológico/fisiología , Miedo/fisiología , Femenino , Preferencias Alimentarias/fisiología , Expresión Génica , Masculino , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Conducta SocialRESUMEN
The effects of peripheral systemic administration of urocortin on operant responding to obtain food were investigated using three separate concentrations. The drug was administered intraparitoneally at a concentration of 10 microg/ml/Kg, 5 microg/ml/Kg, and 0 microg/ml/Kg suspended in saline at a volume of 1 ml/Kg to Sprague-Dawley rats fifteen minutes prior to being exposed to an operant bar press task. Eleven subjects were used, each receiving a single injection of each concentration on separate days with the order of treatment counterbalanced. The results indicated that the administration of urocortin in a dose dependent manner reduced responding of food deprived subjects for a food reward in a thirty minute session. These data indicated that the peripheral administration of urocortin reduced the motivation of food deprived subjects to respond.
Asunto(s)
Condicionamiento Operante/efectos de los fármacos , Hormona Liberadora de Corticotropina/farmacología , Alimentos , Recompensa , Animales , Hormona Liberadora de Corticotropina/administración & dosificación , Inyecciones Intraperitoneales , Masculino , Motivación , Ratas , Ratas Sprague-Dawley , UrocortinasRESUMEN
During starvation, a series of changes in whole body fuel use occur that result in conservation of fuel, particularly protein. Use of fat stores for ketone production and direct oxidation of fat as a primary fuel are characteristic of starvation. However, the mechanism by which this change develops is unclear. Carnitine is an important compound in the control of fat metabolism, since long-chain free fatty acids must be coupled with it to cross the mitochondrial membrane. This study attempts to define, in the fasting dog model, the interaction between plasma and muscle carnitine, its acyl esters, and the energy substrates available. Eight adult beagle dogs were studied during an 8-day period of starvation. Muscle and plasma were analyzed for free carnitine (FC), acid-soluble fraction, and long-chain esters (LCE), as well as substrate hormone profiles. Total carnitine (TC) and short-chain esters (SCE) were calculated. Muscle was analyzed for carnitine palmityl transferase activity (CPT). These measurements were performed on days 3, 5, and 8. There was a significant (p less than 0.05) loss in weight on days 3, 5, and 8. TC and FC increased significantly (p less 0.05) only on day 8; this occurred simultaneously with a significant (p less than 0.05) decrease in CPT. It was preceded by a significant (p less than 0.05) and persistent increase in plasma TC, FC, and LCE that developed on day 3. During starvation there was an increase in plasma carnitine levels before changes in muscle. The increase in muscle carnitine occurred between days 5 and 8 of starvation and seemed to be associated with a fall in CPT. This may be responsible either for or secondary to the decrease in metabolic rate that occurs during prolonged starvation.