Spatial memory impairment is well documented in old age; however, less is known about spatial memory during middle age. We examined the performance of healthy young, middle-aged, and older adults on ...a spatial memory task with varying levels of spatial similarity (distance). On low similarity trials, young adults significantly outperformed middle-aged adults, who significantly outperformed older adults (Ps < 0.05). On high similarity trials, young adults significantly outperformed middle-aged and older adults (Ps < 0.05); however, middle-aged and older adults did not differ. Subtle age-related changes in spatial memory may emerge during middle age, particularly when spatial similarity is high.
Objective: This study aimed to determine the combined effects of age and HIV infection on the risk of incident neurocognitive disorders. Method: A total of 146 neurocognitively normal participants ...were enrolled at baseline into one of four groups based on age (≤40 years and ≥50 years) and HIV serostatus resulting in 24 younger HIV−, 27 younger HIV+, 39 older HIV−, and 56 older HIV+ individuals. All participants were administered a standardized clinical neuropsychological battery at baseline and 14.3 ± .2 months later. Results: A logistic regression predicting incident neurocognitive disorders from HIV, age group, and their interaction was significant (χ
2
4 = 13.56, p = .009), with a significant main effect of HIV serostatus (χ
2
1 = 5.01, p = .025), but no main effect of age or age by HIV interaction (ps > .10). Specifically, 15.7% of the HIV+ individuals had an incident neurocognitive disorder as compared to 3.2% of the HIV− group (odds ratio = 4.8 1.2, 32.6). Among older HIV+ adults, lower baseline cognitive reserve, prospective memory, and verbal fluency each predicted incident neurocognitive disorders at follow-up. Conclusions: Independent of age, HIV infection confers a nearly fivefold risk for developing a neurocognitive disorder over approximately one year. Individuals with lower cognitive reserve and mild weaknesses in higher-order neurocognitive functions may be targeted for closer clinical monitoring and preventative measures.
Computational models and electrophysiological data suggest that the CA3 subregion of the hippocampus supports the formation of arbitrary associations; however, no behavioral studies have been ...conducted to test this hypothesis. Rats with neurotoxin-induced lesions of dorsal dentate gyrus (DG), CA3, or CA1 were tested on object-place and odor-place paired-associate tasks to test whether the mechanism that supports paired-associate learning is localized to the CA3 subregion of the dorsal hippocampus or whether all hippocampal subregions contribute to paired-associate learning. The data indicate that rats with DG or CA1 lesions learned the tasks as well as controls; however, CA3-lesioned rats were impaired in learning the tasks. Thus, the CA3 subregion of the dorsal hippocampus contains a mechanism to support paired-associate learning.
TCR-induced NF-AT activation leads to the up-regulation of multiple genes involved in T cell anergy. Since NF-AT is also involved in T cell activation, we have endeavored to dissect TCR-induced ...activating and inhibitory genetic programs. This approach revealed roles for the early growth response (Egr) family of transcription factors and the Egr coactivator/corepressor NGFI-A-binding protein (NAB)2 in regulating T cell function. TCR-induced Egr-1 and NAB2 enhance T cell function, while Egr-2 and Egr-3 inhibit T cell function. In this report, we demonstrate that Egr-2 and Egr-3 are induced by NF-AT in the absence of AP-1, while Egr-1 and NAB2 both require AP-1-mediated transcription. Our data suggest that Egr-3 is upstream of Egr-2, and that mechanistically Egr-2 and Egr-3 suppress Egr-1 and NAB2 expression. Functionally, T cells from Egr-2 and Egr-3 null mice are hyperresponsive while T cells from Egr-3 transgenic, overexpressing mice are hyporesponsive. Furthermore, an in vivo model of autoimmune pneumonitis reveals that T cells from Egr-3 null mice hasten death while Egr-3-overexpressing T cells cause less disease. Overall, our data suggest that just as the Egr/NAB network of genes control cell fate in other systems, TCR-induced Egr-1, 2, 3 and NAB2 control the fate of antigen recognition in T cells.
This experiment was designed to determine whether adding a temporal component to an object-odor association task would recruit the hippocampus. The rats were given CA1, CA3, or control lesions prior ...to learning the object-trace-odor task. Rats were presented with an object for 10 s, after which the object was removed, followed by a 10-s trace period, followed by the presentation of an odor 50 cm away. If the odor and the object were paired, rats were to dig in the odor cup for a reward. If unpaired, rats were to refrain from digging. Rats that had CA1 lesions were unable to make the association, whereas rats that had CA3 lesions performed as well as controls. These results support the idea that the hippocampus is involved in forming arbitrary associations that do not necessarily involve space as long as they involve a temporal component.
Recall and recognition memory abilities are known to decline with increasing age, yet much of the evidence stems from studies that used simple measures of total target recall or recognition. The ...California Verbal Learning Test-Second Edition (CVLT-II) includes a new measure of recall discriminability that is analogous to recognition discriminability. These discriminability measures yield more thorough assessments of recall and recognition by accounting for intrusion and false positive errors, respectively. Research also has shown that women outperform men on verbal episodic memory tests. However, gender differences in recall and recognition discriminability and the age-by-gender interaction on these constructs have not been thoroughly examined.
Cognitively healthy adults (N = 223) 18-91 years in age completed the CVLT-II. Multiple regression analyses were conducted to examine effects of age, gender, and the age-by-gender interaction on CVLT-II subtypes of recall and recognition discriminability.
Discriminability scores decreased with increasing age, and women outperformed men. There was an age-by-gender interaction on total, immediate, and free recall discriminability - the negative association between age and scores was stronger in men than in women. Exploratory analyses revealed an inverted U-shaped relationship between age and recall discriminability scores in women.
The present findings support and expand upon the extant literature on aging, gender, and verbal episodic memory, plus describe a novel age-by-gender interaction intrinsic to subtypes of recall discriminability. The findings suggest that methods traditionally used to assess recognition memory function can be used to elucidate age- and gender-related changes in recall ability across the adult lifespan.
Individuals with Parkinson's disease (PD) are at risk for increased medication mismanagement, which can lead to worse clinical outcomes. However, the nature of the errors (i.e., undertaking or ...overtaking medications) contributing to mismanagement and their relationship to cognition in PD is unknown. Therefore, this study sought to examine errors committed on the Medication Management Ability Assessment (MMAA) between PD participants with normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) relative to healthy adults (HA).
HA (n = 74), PD-NC (n = 102), and PD-MCI (n = 45) participants were administered the MMAA to assess undertaking, overtaking, and overall errors as well as overall performance (total score). Additionally, participants were administered a comprehensive neuropsychological battery from which cognitive composites of Attention, Learning, Memory, Language, Visuospatial, and Executive Functioning were derived.
Separate negative binomial regression analyses indicated the PD-MCI group performed significantly worse overall on the MMAA (total score) and committed more undertaking and overall errors relative to HA and PD-NC. In the PD-MCI group, poorer MMAA performance was associated with worse delayed memory performance, whereas cognitive performance was not related to MMAA in HA or PC-NC.
Compared to PD and healthy adults with normal cognition, PD-MCI patients exhibited greater difficulty with medication management, particularly with undertaking medications. Poorer medication management in PD-MCI was associated with worse delayed recall. Thus, PD-MCI patients experiencing memory problems may require additional assistance with their medications. Findings have clinical relevance suggesting that objective measures of medication errors may assist clinicians in identifying PD patients needing adherence strategies.