Browsing by Subject "Memory disorders"

Now showing 1 - 2 of 2

Metabolic impairment of the posterior cingulate cortex and reversal by methylene blue: a novel model and treatment of early stage Alzheimer's disease
(2007-12) Riha, Penny Denise, 1975-; Gonzalez-Lima, Francisco, 1955-
Alzheimer's disease (AD) is associated with decreased brain energy metabolism. Hypometabolism in the posterior cingulate cortex (PCC) occurs before the onset of memory deficits in subjects at genetic risk for AD who are not yet cognitively impaired. There is a specific inhibition in cytochrome oxidase (C.O.) in the PCC, an area involved in spatial navigation. Creating an animal model that exhibits the early pathophysiology of AD is important for developing and testing drugs that could reverse memory problems associated with such deficits. Methylene blue (MB) is a compound that improves C.O. activity and memory retention in rats. This dissertation had three specific aims: 1) to examine if isolated PCC hypometabolism causes spatial memory deficits in rats; 2) to find a dose of MB that improves memory without nonspecific behavioral effects; and 3) to prevent memory deficits from PCC hypometabolism with low dose MB. PCC hypometabolism was produced by focal administration of sodium azide, an inhibitor of C.O. activity. PCC hypometabolism resulted in impaired spatial memory in a hole board food-search task, increased oxidative damage, and neurotoxicity in the PCC. In addition, PCC hypometabolism resulted in reduced inter-regional correlations in brain activity. Our second set of studies examined the dose-response effects of MB. Our findings demonstrated that a low dose of MB: 1) enhanced memory in open field habituation and object recognition tasks; 2) did not affect general locomotor activity, exploration, motivation, or anxiety; and 3) increased brain oxygen consumption 24 hr after in vivo administration. Finally, our last study found that low dose MB prevented the deficits caused by PCC hypometabolism. MB did not prevent PCC inhibition or cell loss caused by sodium azide. Inter-regional correlations of brain metabolic activity suggested that rats treated with MB were using a different, but equally efficient, strategy for memory retrieval. This animal model of C.O. hypometabolism in the PCC can provide information to understand the mechanisms that regulate early pathological degeneration and reveal new therapeutic strategies aimed at reducing or preventing cognitive decline. Studies of low dose MB in humans are needed to examine its effects in AD patients.
Prospective memory and medication adherence in schizophrenia : influencing factors and awareness of abilities
(2008-08) Ritch, Janice Lorraine; Beevers, Christopher G.; Tucker, David M., 1953-
Adherence to antipsychotic medication in schizophrenia has been shown to predict symptom exacerbations; however, adherence remains poor in this population. The concept of taking medication on a maintenance regime is an example of prospective memory (PM). The current investigation is comprised of three studies in which 59 outpatients diagnosed with schizophrenia completed a comprehensive assessment including measures of PM, executive functioning, comprehension of medication instructions, insight into the need for medication, and environmental variables supporting adherence. An objective measure of medication adherence was also collected during a one-month baseline period. In study 1, medication adherence was conceptualized as a PM task and variables for predicting adherence based on PM literature were examined. Of the hypothesized variables, the interactive effect of PM ability and comprehension of medication instructions was the only predictor of adherence to antipsychotic medication. Comprehension of medication instructions alone was the only predictor of adherence to total psychotropic medication regime. Study 2 investigated the role of executive functions in the awareness of PM deficits and use of compensatory strategies. Results indicated that patients with poorer executive skills were less reliable in their report of PM ability compared to performance on PM measures. However, both fair and poor executive functioning groups reported similar use of compensatory strategies. Lastly, the third study manipulated the specificity of retrieval context for a 5-day habitual PM task intended to mimic medication-taking. The aim of this investigation was to examine the effect of retrieval context specificity and executive functioning on task performance. Results demonstrated that patients categorized as fair executive functioning completed significantly more days of the habitual task than patients categorized as poor executive functioning. There was no difference in performance between patients receiving greater retrieval context specificity versus patients receiving a general context. However, there was a trend for individuals with fair executive functioning to benefit from greater retrieval context specificity, implying that a minimum level of executive skill may be necessary for individuals to recognize the risk of a restricted retrieval interval and/or mobilize additional resources for encoding. Clinical implications are discussed.