Paul Merritt

Evidence that androgenic and estrogenic metabolites contribute to the effects of dehydroepiandrosterone on cognition in postmenopausal women

Prior studies of the effects of dehydroepiandrosterone (DHEA) on cognition have produced complex and inconsistent results. We hypothesize that these results may arise, in part, because of DHEAs metabolism into estrogens and androgens that produce opposing effects on cognition. Our study administered 50 mg of oral DHEA daily for 4 weeks in a placebo-controlled crossover design to six postmenopausal women. We measured blood levels of androgens (total testosterone, free testosterone, DHEA, DHEAS), estrogens (estradiol, estrone), and cognitive performance on recognition memory, perceptual identification, digit span memory, and visual attentional vigilance under both drug and placebo conditions. Multiple regression models incorporating the factors of age and body mass index (BMI) were used to ascertain the relation between sex steroids and cognitive performance. Our results demonstrated that estrogens produced a positive effect on recognition memory, while androgens produced a negative effect. This pattern reversed in perceptual identification with estrogens producing a negative effect and androgens producing a positive effect. In addition, BMI produced a negative effect on digit span memory, age produced a negative effect on perceptual identification, and androgens produced a negative effect on visual attentional vigilance. These results help, in part, to explain DHEAs complex effects on cognition. The diverse effects of sex steroids across tasks underscore the importance of identifying the specific cognitive mechanisms influenced by sex steroids and emphasizes that one should not expect sex steroids to produce homogeneous effects across cognitive tasks.

Effects of word frequency on individual-item and serial order retention: tests of the order-encoding view.

The orderencoding view of the word frequency effect proposes that low-frequency (LF) items attract more attention to the encoding of individual-item information than do high-frequency (HF) items, but at the expense of order encoding (DeLosh & McDaniel, 1996). When combined with the assumption that free recall of unrelated words is organized according to their original order of presentation, this view explains the finding that HF words are better recalled than LF words in pure lists but that, in mixed lists, recall is better for LF words. The present study confirmed that in mixed lists, order memory becomes equivalent for HF and LF words and that the predicted pattern of order memory and recall holds for incidental order-encoding conditions, for longer lists than those used in previous experiments, and for lists with minimal interitem associativity. Moreover, recall from HF lists declined, but recall from LF lists improved, in related-word lists, relative to unrelated-word lists, reversing the usual pure-list free recall advantage for HF words. These results were uniquely predicted by the orderencoding account and favor this view over accessibility, interitem association, and cuing effectiveness explanations of the word frequency effect.

Metamemory without the memory: are people aware of midazolam-induced amnesia?

RationaleMidazolam is a benzodiazepine which produces a dense anterograde amnesia, while permitting relatively well-preserved short-term memory, semantic retrieval, and other higher cognitive functions. Given these preserved abilities, we were interested in whether or not participants given midazolam would be aware of this anterograde amnesia.MethodIn the present experiment, participants were given midazolam in one testing session and a saline placebo in another. Participants provided judgments-of-learning (JOLs) immediately following study of cue-target pairs. During the test phase of the experiment, confidence levels and feeling-of-knowing (FOK) judgments were collected.ResultsAlthough cued recall performance was substantially impaired in the midazolam condition, mean JOLs were unaffected, indicating participants had little insight into their impairment during the study phase. Participants were relatively accurate in confidence levels and FOK judgments in the midazolam condition.ConclusionWhen studying items under the influence of midazolam, participants are unaware that their memory will be impaired. Implications for clinical practice and pharmacological studies of amnesia are discussed.

Lower blood pressure correlates with poorer performance on visuospatial attention tasks in younger individuals

The relationship between low blood pressure and cognitive function among younger individuals is not fully understood. While a number of studies have examined hypertensive and hypotensive individuals, particularly in older populations, little attention has been devoted to healthy, young populations. We tested 105 healthy young individuals whose blood pressure levels naturally fell in the below normal-to-normal range. Our primary finding was a positive relation between blood pressure and cognition, as measured by two visuospatial attention tasks. This relation appears to be specific to visuospatial skills, as no relationship was observed between recognition memory and blood pressure. We discuss possible explanations for this positive relationship, such as structural neural mechanisms, and how they apply to the overall blood pressure-cognition relationship.

Sex differences in the cognitive effects of tobacco abstinence: a pilot study

Despite significant research demonstrating the deleterious effects of tobacco abstinence on memory, and research showing substantial sex differences in nicotine withdrawal and memory processes, there has been scant work on how males and females might differ in the effects of tobacco abstinence on memory and cognition. Using a standard recognition memory task, we conducted a pilot study to examine how 24 hours of tobacco abstinence in moderate to heavy smokers would affect memory in males and females. Twenty-five moderate to heavy smokers were tested following a period of smoking normally and following 24 hours of tobacco abstinence. At each session, participants completed a recognition memory task in which items were studied under full- and divided-attention conditions (a standard manipulation of memory encoding) as well as tests of passive short-term and working memory (forward and backward digit span). Tobacco abstinence significantly reduced memory performance under full attention conditions for males but not for females. A significant main effect of smoking status in which abstinence significantly reduced performance, as well as a main effect of encoding condition (divided attention < full attention), were found. Our results demonstrate that there may be substantial sex differences in the cognitive effects of tobacco abstinence. While preliminary, the data suggest the need for further, more extensive study of how males and females differ during tobacco abstinence. Such information will inform the best strategies for tobacco cessation efforts.

Evidence That Episodic Memory Impairment During Tobacco Abstinence Is Independent of Attentional Mechanisms

ABSTRACT Previous studies have demonstrated reductions in episodic memory during nicotine withdrawal. However, these studies have been unable to dissociate memory reductions from losses in attention associated with tobacco abstinence. In the present study, the authors sought to determine whether episodic memory reduction is a primary effect of nicotine withdrawal during tobacco abstinence. Heavy smokers were tested when smoking normally and following 24 hrs of abstinence. Participants were tested with a recognition memory task in which items were studied under full and divided attention conditions. Forward digit span and backward digit span were also included as control measures. Withdrawal was associated with a reduction in memory performance that was independent of attention at encoding. The authors conclude that impairment of episodic memory is a primary effect of nicotine withdrawal during tobacco abstinence. Further research is required to determine if this is associated with continued use of tobacco and cessation failures.

Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women

The current study examines the effect of administering dehydroepiandrosterone (DHEA) on short-term memory. This experiment used a double-blind placebo-controlled cross-over design to explore the effects of a four week regimen of 50 mg oral DHEA on performance on the digit span, verbal span, and modified Sternberg (Oberauer) tasks. The results demonstrate that the current regimen of drug administration significantly increases serum levels of DHEA, DHEAS, testosterone and estrone and substantially alters the patterns of correlations among the serum levels of these hormones. Despite this substantial change in the hormonal milieu, DHEA administration produced no beneficial effects on cognitive performance in the digit span, verbal span, or modified Sternberg paradigm tasks. Ancillary analyses of the relation between hormone levels and cognitive performance demonstrated a strong positive correlation between DHEA levels and performance on digit span forward/backward and verbal span forward in the placebo drug condition, but not in the DHEA condition. We interpret the juxtaposition of the null results of DHEA administration and the correlation of DHEA levels and performance in the placebo condition to indicate that the referenced correlations arise because a third variable (i.e., age) is associated with both performance and DHEA levels. Additional analyses supported this hypothesis.