HIV-associated neurocognitive deficits, particularly in the area of working memory, are highly prevalent in older adults (e.g., Valcour, Shikuma, Watters, et al., 2004
), suggesting a need to identify protective factors that may inform rehabilitation efforts in this growing subset of the HIV-infected population. Therefore, this study sought to examine whether spontaneous strategy use protects against working memory deficits in older adults living with HIV. Consistent with prior research (e.g., Wegesin et al., 2000
), we observed a main effect of strategy use, such that individuals who used a mnemonic strategy during the SOPT performed better than those who did not. However, this main effect was tempered by an interaction between strategy use and age; i.e., older adults with HIV who used a mnemonic strategy made fewer errors than their older seronegative counterparts who did not employ strategies, but there was no effect of strategy use in the young HIV+ adults. In other words, older HIV+ adults who grouped designs by visual details were better able to correctly identify novel targets on the SOPT, which requires an individual to generate, monitor, and maintain a response set to a series of repeated complex visual stimuli. In fact, older adults who implemented a strategy performed comparably to YSUs and significantly better than
younger adults who did not use a strategy. Importantly, this finding was associated with a large effect size and remained significant after considering various demographic and disease characteristics that might otherwise have confounded the analyses (e.g., education). As such, these findings suggest that working memory declines in older HIV-infected adults may be moderated by the use of higher-level mnemonic strategies.
This study provides the first glimpse into the cognitive mechanisms of working memory impairment in older adults with HIV by suggesting that such deficits may be driven, at least in part, by deficiencies in strategy deployment. Our results are consistent with the literature on HIV-associated decrements in the strategic aspects of cognition (e.g., Gongvatana, Woods, Taylor, Vigil, & Grant, 2007
; Woods, Dawson, Weber, Grant, & The HNRC Group, 2010
), as well as frontostriatal neural injury in HIV infection (e.g., Chang et al., 2003
) and aging (Drachman, 2006
), which are brain regions integral to the strategic aspects of working memory (Collette & Van der Linden, 2002
). Indeed, it has been hypothesized that HIV-associated working memory deficits are secondary to dysregulation of the central executive (cf. sensory slave systems), as outlined by Baddeley's model of working memory (Hinkin et al., 2002
). NeuroAIDS imaging research also supports the link of frontal systems impairment by the pattern of abnormal blood oxygenation level-dependent signals in frontoparietal pathways during high cognitive load working memory tasks, which arguably require greater involvement of the central executive (Ernst et al., 2003
). Similar patterns of increased levels of prefrontal activation are seen in healthy older adults during tasks involving greater working memory demands (e.g., Emery, Heaven, Paxton, & Braver, 2008
), which suggests that the strategic aspects of working memory may be differentially affected in older adults (Bopp & Verhaeghen, 2005
). In fact, older HIV+ adults are at increased risk for fronto-striato-thalamo-cortical circuitry dysfunction (Chang et al., 2008
), including impairment in working memory (Cherner et al., 2004
) and the strategic aspects of prospective memory (Woods et al., 2010
Concurrent validity of this interpretation is supported by analysis of measures of executive functions and estimated verbal intelligence that were conducted within the older cohort. Specifically, OSUs demonstrated higher estimated premorbid VIQs, made significantly fewer moves during a novel problem-solving task, were more likely to spontaneously deploy a semantic clustering strategy on the CVLT-II, and were slightly faster in completing the TMT B. Together, these data suggest that the observed effects of this meta-cognitive approach may be generalizable from visual working memory because spontaneous strategy users were also more effective in navigating the demands of other complex cognitive tasks. In contrast, there was no effect of strategy use on measures of basic verbal working memory or information processing speed. Whether strategy use also generalizes to better daily functioning outcomes (e.g., employment, medication management, etc.) remains to be determined. Such efforts may shed some additional light on the cognitive aging paradox whereby a subset of older adults demonstrates superior everyday functioning (e.g., medication adherence) on semi-naturalistic assessments despite poorer performance on cognitive tasks in the laboratory (e.g., Rendell & Craik, 2000
Non-cognitive factors might also play a role in determining whether one develops, deploys, and benefits from using a strategy during working memory tasks; in other words, individuals who implement strategies may be inherently different from those who do not. Indeed, across the entire cohort, strategy use was associated with higher cognitive reserve, including more educational attainment and higher estimated VIQ. This is consistent with prior studies showing that cognitive reserve may play an important role in the expression of executive dysfunction in HAND (Basso & Bornstein, 2000
). Specific to the older group, who benefited most from spontaneously deploying mnemonic aids, strategy users were better educated, had higher estimated VIQs, and were less likely to have histories of stimulant dependence. Nevertheless, even when these potentially confounding factors were considered in the statistical model, the effects strategy use and age group remained a significant predictor of working memory performance.
Unexpectedly, the OSUs also had more advanced HIV disease, including longer duration of infection and higher rates of AIDS diagnoses, which represent a conservative bias. This is particularly interesting given the compelling research on historic immune compromise and risk of HAND (e.g., Valcour, Shikuma, Shiramizu, et al., 2004
; Valcour, Shikuma, Watters, & Sacktor, 2004
). Although this counterintuitive finding may be spurious and/or reflect a survival bias, it is also possible that OSUs have greater cognitive reserve, as supported by the independent effects of VIQ in the final regression model. There may be, however, more subtle and unexplored differences in CNS (e.g., brain reserve) or psychosocial (e.g., wisdom, social support) factors, which are important in the successful cognitive aging literature, that further explain age-related differences in the efficacy of strategy use and warrant further study.
Having ruled out the influence of several possible confounding factors, these results then raise questions about how and why older HIV+ adults may spontaneously generate and utilize meta-cognitive strategies. Considering the cognitive findings reported above, it may the decision that a strategy would be necessary for optimal performance may be controlled by an individual's insight into their cognitive deficits, as well as appropriate assessment of the nature and complexity of the task at hand. Second, the generation and selection of a strategy requires that an individual has learned and can activate the necessary tools to devise appropriate strategies for given situations. Next, the individual must be able to effectively deploy the decided-upon strategy, drawing upon available cognitive and environmental resources. Elements of cognitive control/flexibility may also be required to modify the selected strategy if it is determined that the deployed technique is ineffective. Finally, after task completion, one must evaluate the effectiveness of a strategy with the ability to make an unbiased assessment of task performance. The complex array of cognitive skills required for successful spontaneous strategy implementation suggests that not only is strategy use ability multidetermined, but that there may be various avenues through which to intervene.
The study sample and methods have several limitations that are worth consideration. First and foremost, we did not have access to a group of demographically comparable seronegative adults with SOPT data. As such, these findings do not directly speak to an HIV effect on working memory, but rather interpretations are restricted to age effects among HIV+ individuals. In addition, the relatively small samples of strategy users within the old and young groups may have increased our risk of type II error for some analyses. For example, although there were no significant SOPT differences based on strategy use in the younger group, we may have been underpowered to detect this effect, which was associated with a medium effect size. Another major limitation of the present study is that we measured strategy use with a single self-report item that was administered after the completion of the SOPT and did not include a post-test validation check. Although this is a commonly used and well-validated methodology (e.g., Roth et al., 2004
), future investigators may wish to prospectively examine the specific component processes of strategy generation and use. Finally, we did not consider the possible role of psychotropic medications (e.g., Letendre et al., 2007
), smoking (e.g., Durazzo et al., 2007
), or recent substance use, which may have influenced our findings (we excluded individuals with substance abuse or dependence within 6 months of evaluation).
Although the present results suggest that spontaneous strategy use may be protective against working memory impairment, they also raise the question of whether didactic administration of working memory strategies through cognitive rehabilitation in this cohort would be equally effective. Recent attempts to provide explicit intensive cognitive training have been largely successful in remediating working memory and executive functioning deficits across several conditions, including multiple sclerosis (e.g., Flavia, Stampatori, Zanotti, Parrinello, & Capra, 2010
) and TBI (e.g., Vallat-Azouvi, Pradat-Diehl, & Azouvi, 2009
). Examining the specific strategy use components as proposed would be helpful in determining whether it is “strategy generation or strategy instruction” that could be protective against working memory deficits, as other studies in neurologic populations have noted normal performance by patients in the generation condition but worse performance when instructed to use a particular strategy (Goebel, Mehdorn, & Leplow, 2010
). In order to better address the question at hand (as related to our study limitations), it would be beneficial for future research to examine this issue prospectively in a randomized fashion, and with attention paid to cognitive characteristics within the sample (e.g., working memory impairment) as well as strategy generalizability.
Despite the theoretical evidence to support our findings, existing literature on strategy use in older adults to improve working memory have produced mixed results. For example, Duverne, Lemaire, and Vandierendonck (2008
) demonstrated that older adults might not benefit from the use of strategies in arithmetic-based working memory tasks due to the overall impact of cognitive slowing on task performance. Similarly, Bailey and colleagues (2009)
found that performance on reading and operation span tasks were related to differences in processing speed between younger and older adults as opposed to differential strategy use. Other studies have indicated that both younger and older adults benefit equally from strategy use training on a working memory task and that there is no differential benefit (or deficit to the remediated) between groups (Carretti, Borella, & De Beni, 2007
). More basically, there is some controversy over whether it is the strategic aspects (cf. automatic components) of working memory that impede performance in older adults, which may then help explain why strategy-based interventions are not differentially beneficial in this group (e.g., Rose, Bowman, Radziewicz, Lewis, & O'Toole, 2009
). To our knowledge, strategy-based rehabilitation of working memory deficits (or other cognitive impairments) have yet to be explored in the context of aging and HIV infection, but our results suggest that such efforts may be worthwhile.
Indeed, it is surprising that cognitive rehabilitation approaches have not yet been developed for persons with HAND. In general, the mild-to-moderate cognitive deficits in memory and executive functions associated with HIV-related impairment lend themselves well to established intervention strategies (e.g., self-monitoring, external reminders). For example, while numerous studies (e.g., Gongvatana et al., 2007
) have demonstrated spontaneous strategy use deficiency during learning and memory tasks in individuals with HIV, it has not been explored whether implementation of a strategy can remedy such deficits. Importantly, the current classification and treatment of HIV as a chronic illness provides a large window for intervention possibilities and long-term use of rehabilitation gains. Numerous studies in other disorders have established that cognitive rehabilitation may help reduce the risk of functional declines (e.g., acquired brain injury; Spikman, Boelen, Lamberts, Brouwer, & Fasotti, 2010
), which is highly relevant in HIV considering the importance of daily tasks (e.g., antiretroviral adherence) to health outcomes. Clinical deployment of such cognitive neurorehabilitation strategies with older HIV+ adults, however, is not yet indicated and awaits a demonstration of effectiveness through careful, prospective research.