Dennis Deptula

CSF corticotropin-releasing factor (CRF) in Alzheimer's disease: its relationship to severity of dementia and monoamine metabolites

The concentration of corticotropin-releasing factor-like immunoreactivity (CRF-LI) in the cerebrospinal fluid (CSF) of 15 probable Alzheimers disease (AD) patients with mild to moderate dementia and 10 neurologically normal age-matched controls was examined. There were no significant alterations in the mean CSF CRF-LI concentration in AD compared to controls. However, in the AD group, CSF CRF-LI correlated significantly with the global neuropsychological impairment ratings, suggesting that greater cognitive impairment was associated with lower CSF CRF-LI concentrations. There was a significant reduction in the CSF concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the AD patients, and there was a positive correlation between the concentration of CRF-LI and 5-HIAA in CSF. This latter finding suggests that serotoninergic neuronal systems may interact with CRF-containing neurons.

Effects of antidepressants on human performance: a review.

Despite widespread use of antidepressants, major gaps remain in our knowledge of the effects of antidepressants on human performance. While most single-dose studies with normal subjects have suggested that the more sedating tricyclic antidepressants tend to produce impairment, the effects of antidepressant treatment in clinical populations have been less thoroughly examined, with both drug-induced impairment and improvement reported. This review suggests that factors such as age, diagnosis, drug plasma concentration, and length of treatment need to be explored to establish the effects of antidepressants on performance in clinical populations.

Loss of the cortisol response to naltrexone in Alzheimer's disease

The administration of a single dose of the opiate antagonist naltrexone (NT) was accompanied by significant elevations in plasma cortisol in normal elderly subjects; in contrast, the cortisol response to NT was absent in individuals of comparable age with Alzheimers disease (AD). The differential effect of AD on the cortisol response was not accompanied by a significant group difference in plasma prolactin in response to NT administration. Furthermore, this differential cortisol response to NT was not associated with any evident differences in age, sex ratio, plasma levels of naltrexone or its major metabolite beta-naltrexol, or with differences in measures of nonspecific stress, such as plasma free MHPG, pulse, or blood pressure, between the two groups. The absence of the well-characterized cortisol response to NT in AD, together with other reports of abnormal responses to other pharmacological challenges, suggests that neuroendocrine abnormalities might be an important concomitant and possibly a central contributor to the pathophysiology of Alzheimers disease.

EQUIVALENCE OF FIVE FORMS OF THE SELECTIVE REMINDING TEST IN YOUNG AND ELDERLY SUBJECTS

This study evaluated the equivalence of five forms of the Selective Reminding Test, a widely used measure of verbal learning. 45 normal young and 45 normal elderly subjects were randomly administered three of the five test forms on three separate sessions. The five forms generally correlated well with one another and were of comparable difficulty, suggesting adequate test equivalence. Four of the five forms were particularly well matched.

192. Alprazolam and lorazepam: Memory impairment on successive learning trials

We havepn%ouslyreportedthatacutehighandlowdosesof alprazohrm (ALP,0.25mg,0.5mg)and lorazepam(LOR,0.5mg, lmg), whichare thoughtobeequivalent inanxiolyticeffects, impairedmemoryperformance ona verballist learningtask(Buschke’sSeIectiveRemindingTask).These findings,however,werebasedon thecumulativerecallof 7 learning trials (totalmall). In the presentanalysis,we examinedthe acuteand chronic effects of these drugs on recall across the 7 trials. Acute effects were examinedbothbeforeandafterchronicb.i.d.treatmentin a doubleblind placebo-control, parallelstudyinhealthyelderly.Initialacutechallengewith singlehighdosesofbothdrugsresultedinsi@lcantdmg x trialinteractions in whichthe dreg-inducedimpairmentsbecamegreateroverthe courseof successivetrialsat i and 2.5 hourspost-drug. No sigMcant drugx kid interactionswerefoundduringchronictreatment.Afterchronictreatment, only acute techallengewith the single high dose of LOR resultedin increasedimpairment acrossthe7 trialsrelativetoplaceboat2.5hours(drug x trkdinteraction). RerhalIengewiththehighdoseofALPno longercaused such increasedimpairment.This suggeststhat toleranceto the adverse effectsof acuterechallengeon recallacrossthe 7 trialsis momlikelyto developas a resultof chronictreatmentwiththe highdoseof ALP.Low dosesof thetwodrugsproducednosignificant drngxtrialinteractions either in theinitialacutechallengeorrechailengeinspiteofsigMcant impairment in totrdredl.

The effects of iorazepam and alprazolam on cognition in the elderly

Benzodiazepines with shorter elimination half-lives are widely prescribed In the elderly and generally thought to produce less cognitive toxicity than agents with longer half-lives such as diazepam. However, there are few stud• ies that have examined the cognitive effects of these agents In the elderly. This study assessed the acute and chronic effects on task perfonnance of high and low equivalent doses of alprazolam and lorazepam, two benzo• diazepines with relatively short half-lives. The relationship of these effects to age, plasma drug levels and duration of treatment was also examined. Eighty subjects (ages~7 yrs) participated In an NIMH-sponsored 3-week double-blind, placebo-controlled, parallel group study comparing low(0.25 mg bid) and hlgh-close (0.5 mg bid) alprazolam versus low(0.5 mg bid) and high-dose (1.0 mg bid) lorazepam. Both low and high doses of alprazolam and lorazepam produced significant impairments in the Buschke total recall in the Initial acute challenge. Chronic treatment was associated with minimal next-day effects. Acute rechallenge with high doses of alprazolam and 10• razepam after 3 weeks of chronic treatment was associated with significant less impairment than that observed In the Initial acute challenge, consistent with the development of tolerance. Nevertheless, rechallenge with low doses of lorazepam and alprazolam and high doses of lorazepam still produced significant Impairment compared to placebo. These findings suggest caution In the use of these medications In the elderly.

The relationship of aging and plasma cortisol to memory and attention

342 Twenty-three had been switched to placebo while 13 and 15 were kept on nortriptyline and phenelzine, respectively. Patients on phenelzine did significantly better with 13.3% recurrences than patients on either nortriptyline (53.8% recurrences) or placebo (65.2% recurrences). In addition, patients who had higher Hamilton scores and who had an earlier age of onset of the first depressive episode were significantly more likely to have recurrences.