Understanding the Relations among Episodic Memory, Associative Learning, and Fluid Intelligence in Younger and Older Adults

Age-related changes in episodic memory are hallmarks of aging (Balota, Dolan, & Ducheck, 2000). However, there is still debate as to what underlies episodic memory declines. Two hypotheses, the associative deficit hypothesis (Naveh-Benjamin, 2000) and the environmental support hypothesis (Craik, 1983), were evaluated as possible explanations. The associative deficit hypothesis predicts that age-related differences are greater in tasks that require binding of memory items or features of an item, whereas the environmental support hypothesis argues that age-related differences are greater in tasks that do not provide participants with retrieval cues at the time of test. Under certain circumstances, like those studied here, these hypotheses make different predictions for age-related differences in episodic memory. In order to test these hypotheses, participants completed verbal and spatial versions of three different learning tasks: list recall, paired-associate, and complex association learning. The tasks differed both in the amount of binding required and in the amount of retrieval cues provided at test. The associative deficit hypothesis predicts that age-related differences will be greater on paired-associate and complex association learning tasks relative to performance on list learning tasks. In contrast, the environmental support hypothesis predicts that age-related differences will be greater on list learning tasks relative to performance on paired-associate and complex association learning tasks, both of which provide retrieval cues for support at recall. These three learning tasks not only allowed for the examination of age-related differences in episodic memory, but performance on these learning tasks along with performance on fluid intelligence tasks also allowed for the examination of the predictive utility of learning for individual and age-related differences in fluid intelligence. With respect to this second issue, two separate questions were addressed: First, is complex association learning or general learning ability the better predictor of fluid intelligence, and second, does learning account for unique variance in fluid intelligence after controlling for other cognitive abilities? The second question was addressed in the context of a cognitive cascade model in which the relations among several cognitive variables (i.e., processing speed, working memory, and secondary memory) were examined with learning as a potential mediator of age-related differences in fluid intelligence. In regard to age-related differences in episodic memory, the results of the current study were consistent with the associative deficit hypothesis and provide evidence against the environmental support hypothesis. Age differences were found to be greater on the paired-associate learning task and the complex association learning task relative to the list learning task, consistent with the associative deficit hypothesis but the exact opposite of what is predicted by the environmental support hypothesis. This associative deficit was observed in both initial learning and final learning memory performance, and in both the verbal and spatial domains. Thus, as suggested by Naveh-Benjamin (2000), older adults are more impaired in the ability to encode or retrieve associations as opposed to individual items. Further, associative learning among older adults was an important predictor of fluid intelligence. However, among younger adults, individual differences in learning in general, and not just associative learning, were predictive of fluid intelligence. The present findings demonstrate that learning is an important predictor of fluid intelligence in both young and older adults

Individuals with low working memory spans show greater interference from irrelevant information because of poor source monitoring, not greater activation

Although individuals with high and low working memory (WM) span appear to differ in the extent to which irrelevant information interferes with their performance on WM tasks, the locus of this interference is not clear. The present study investigated whether, when performing a WM task, high- and low-span individuals differ in the activation of formerly relevant, but now irrelevant items, and/or in their ability to correctly identify such irrelevant items. This was done in two experiments, both of which used modified complex WM span tasks. In Experiment 1, the span task included an embedded lexical decision task designed to obtain an implicit measure of the activation of both currently and formerly relevant items. In Experiment 2, the span task included an embedded recognition judgment task designed to obtain an explicit measure of both item and source recognition ability. The results of these experiments indicate that low-span individuals do not hold irrelevant information in a more active state in memory than high-span individuals, but rather that low-span individuals are significantly poorer at identifying such information as irrelevant at the time of retrieval. These results suggest that differences in the ability to monitor the source of information, rather than differences in the activation of irrelevant information, are the more important determinant of performance on WM tasks

Individuals with low working memory spans show greater interference from irrelevant information because of poor source monitoring, not greater activation

Although individuals with high and low working memory (WM) span appear to differ in the extent to which irrelevant information interferes with their performance on WM tasks, the locus of this interference is not clear. The present study investigated whether, when performing a WM task, high- and low-span individuals differ in the activation of formerly relevant, but now irrelevant items, and/or in their ability to correctly identify such irrelevant items. This was done in two experiments, both of which used modified complex WM span tasks. In Experiment 1, the span task included an embedded lexical decision task designed to obtain an implicit measure of the activation of both currently and formerly relevant items. In Experiment 2, the span task included an embedded recognition judgment task designed to obtain an explicit measure of both item and source recognition ability. The results of these experiments indicate that low-span individuals do not hold irrelevant information in a more active state in memory than high-span individuals, but rather that low-span individuals are significantly poorer at identifying such information as irrelevant at the time of retrieval. These results suggest that differences in the ability to monitor the source of information, rather than differences in the activation of irrelevant information, are the more important determinant of performance on WM tasks

Identification of N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1,2 and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies

Pan Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2 and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model and pre-clinical profile of the potent and selective pan PIM kinase inhibitor 8 (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor 1, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability. From this aminocyclohexyl series, 8 entered the clinic in 2012 in multiple myeloma patients and is currently in several phase 1 trials of cancer patients with hematological malignancies

Identification of <i>N</i>‑(4-((1<i>R</i>,3<i>S</i>,5<i>S</i>)‑3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies

Pan proviral insertion site of Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model, and preclinical profile of the potent and selective pan PIM kinase inhibitor compound <b>8</b> (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor compound <b>3</b>, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability. From this aminocyclohexyl series, compound <b>8</b> entered the clinic in 2012 in multiple myeloma patients and is currently in several phase 1 trials of cancer patients with hematological malignancies