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1.  Divergent Trajectories in the Aging Mind: Changes in Working Memory for Affective Versus Visual Information With Age 
Psychology and aging  2005;20(4):542-553.
Working memory mediates the short-term maintenance of information. Virtually all empirical research on working memory involves investigations of working memory for verbal and visual information. Whereas aging is typically associated with a deficit in working memory for these types of information, recent findings suggestive of relatively well-preserved long-term memory for emotional information in older adults raise questions about working memory for emotional material. This study examined age differences in working memory for emotional versus visual information. Findings demonstrate that, despite an age-related deficit for the latter, working memory for emotion was unimpaired. Further, older adults exhibited superior performance on positive relative to negative emotion trials, whereas their younger counterparts exhibited the opposite pattern.
doi:10.1037/0882-7974.20.4.542
PMCID: PMC2746384  PMID: 16420130
emotion; working memory; affect; cognition; positivity effect
2.  Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the “Cortical” Hypothesis 
AIDS and behavior  2011;15(6):1187-1196.
The incidence and prevalence of older adults living with HIV infection is increasing. Recent reports of increased neuropathologic and metabolic alterations in older HIV+ samples, including increased cortical beta-amyloid, have led some researchers to suggest that aging with HIV may produce a neuropsychological profile akin to that which is observed in “cortical” dementias (e.g., impairment in memory consolidation). To evaluate this possibility, we examined four groups classified by HIV serostatus and age (i.e., younger ≤40 years and older ≥50 years): (1) Younger HIV− (n = 24); (2) Younger HIV+ (n = 24); (3) Older HIV− (n = 20); and (4) Older HIV+ (n = 48). Main effects of aging were observed on episodic learning and memory, executive functions, and visuoconstruction, and main effects of HIV were observed on measures of verbal learning and memory. The interaction of age and HIV was observed on a measure of verbal recognition memory, which post hoc analyses showed to be exclusively attributed to the superior performance of the younger HIV seronegative group. Thus, in this sample of older HIV-infected individuals, the combined effects of HIV and aging do not appear to result in a “cortical” pattern of cognitive deficits.
doi:10.1007/s10461-010-9815-8
PMCID: PMC3110599  PMID: 20865313
Human immunodeficiency virus; Aging; Cognition; Neuropsychological tests; Episodic memory
3.  Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the “Cortical” Hypothesis 
AIDS and Behavior  2010;15(6):1187-1196.
The incidence and prevalence of older adults living with HIV infection is increasing. Recent reports of increased neuropathologic and metabolic alterations in older HIV+ samples, including increased cortical beta-amyloid, have led some researchers to suggest that aging with HIV may produce a neuropsychological profile akin to that which is observed in “cortical” dementias (e.g., impairment in memory consolidation). To evaluate this possibility, we examined four groups classified by HIV serostatus and age (i.e., younger ≤40 years and older ≥50 years): (1) Younger HIV− (n = 24); (2) Younger HIV+ (n = 24); (3) Older HIV− (n = 20); and (4) Older HIV+ (n = 48). Main effects of aging were observed on episodic learning and memory, executive functions, and visuoconstruction, and main effects of HIV were observed on measures of verbal learning and memory. The interaction of age and HIV was observed on a measure of verbal recognition memory, which post hoc analyses showed to be exclusively attributed to the superior performance of the younger HIV seronegative group. Thus, in this sample of older HIV-infected individuals, the combined effects of HIV and aging do not appear to result in a “cortical” pattern of cognitive deficits.
doi:10.1007/s10461-010-9815-8
PMCID: PMC3110599  PMID: 20865313
Human immunodeficiency virus; Aging; Cognition; Neuropsychological tests; Episodic memory
4.  An examination of the age-prospective memory paradox in HIV-infected adults 
The age-prospective memory (PM) paradox asserts that, despite evidence of age-associated PM deficits on laboratory tasks, older adults perform comparably to (or better than) young adults on naturalistic PM tasks. This study examined the age-PM paradox in older HIV-infected individuals, who represent a growing epidemic and may be at heightened risk for adverse neurocognitive and everyday functioning outcomes. Participants included 88 older (50+ years) and 53 younger (≤40 years) HIV-infected individuals as well as 54 older and 59 younger seronegative adults who completed both laboratory and naturalistic time-based PM tasks. Similar interactions were observed in both the seropositive and the seronegative samples, such that the older participants demonstrated significantly lower laboratory-based PM than the younger groups, but not on the naturalistic PM trial. Secondary analyses within the HIV+ sample revealed that naturalistic task success was indirectly associated with greater self-reported use of PM-based and external compensatory strategies in the daily lives of older, but not younger, HIV+ adults. Study findings suggest that, although older HIV-infected adults exhibit moderate PM deficits on laboratory measures versus their younger counterparts, such impairments are paradoxically not evident on ecologically relevant naturalistic PM activities in daily life, perhaps related to effective utilization compensatory strategies.
doi:10.1080/13803395.2011.604027
PMCID: PMC3327134  PMID: 21992453
Episodic memory; Aging; Neuropsychological assessment; AIDS dementia complex; Cognition
5.  Combined Effects of Aging and HIV Infection on Semantic Verbal Fluency: A View of the Cortical Hypothesis Through the Lens of Clustering and Switching 
The profile of HIV-associated neurocognitive disorders (HAND) has classically been characterized as “subcortical”, but questions have arisen as to whether aging with HIV in the antiretroviral therapy era has subtlety shifted the expression of HAND into a more “cortical” disorder (e.g., decay of semantic memory stores). We evaluated this hypothesis by examining semantic fluency and its component processes (i.e., clustering and switching) in 257 individuals across four groups stratified by age (<40 and ≥ 50 years) and HIV serostatus. Jonckheere-Terpstra tests revealed significant monotonic trends for the combined effects of HIV and aging on overall semantic (and letter) fluency and switching, but not cluster size, with greatest deficits evident in the older adults with HIV infection. Within the older HIV-infected cohort, poorer switching was uniquely associated with self-reported declines in instrumental activities of daily living and deficits in learning and executive functions, but not semantic memory. Results suggest that HIV infection and aging may confer adverse additive effects on the executive components of semantic fluency (i.e., switching), rather than a degradation of semantic memory stores (i.e., cluster size), which is a profile that is most consistent with combined frontostriatal neuropathological burden of these two conditions.
doi:10.1080/13803395.2011.651103
PMCID: PMC3329578  PMID: 22292479
Immunologic disorders; geropsychology; verbal fluency; executive functions; cognitive neuropsychology
6.  The Relationship between Visual-Spatial and Auditory-Verbal Working Memory Span in Senegalese and Ugandan Children 
PLoS ONE  2010;5(1):e8914.
Background
Using the Kaufman Assessment Battery for Children (K-ABC) Conant et al. (1999) observed that visual and auditory working memory (WM) span were independent in both younger and older children from DR Congo, but related in older American children and in Lao children [1]. The present study evaluated whether visual and auditory WM span were independent in Ugandan and Senegalese children.
Method
In a linear regression analysis we used visual (Spatial Memory, Hand Movements) and auditory (Number Recall) WM along with education and physical development (weight/height) as predictors. The predicted variable in this analysis was Word Order, which is a verbal memory task that has both visual and auditory memory components.
Results
Both the younger (<8.5 yrs) and older (>8.5 yrs) Ugandan children had auditory memory span (Number Recall) that was strongly predictive of Word Order performance. For both the younger and older groups of Senegalese children, only visual WM span (Spatial Memory) was strongly predictive of Word Order. Number Recall was not significantly predictive of Word Order in either age group.
Conclusions
It is possible that greater literacy from more schooling for the Ugandan age groups mediated their greater degree of interdependence between auditory and verbal WM. Our findings support those of Conant et al., who observed in their cross-cultural comparisons that stronger education seemed to enhance the dominance of the phonological-auditory processing loop for WM.
doi:10.1371/journal.pone.0008914
PMCID: PMC2811730  PMID: 20111706
7.  The aggregate effects of multiple comorbid risk factors on cognition among HIV-infected individuals 
This study developed and then cross-validated a novel weighting algorithm based on multiple comorbid risk factors (stimulant use, vascular disease, hepatitis C, HIV disease severity, cognitive reserve) to predict cognitive functioning among 366 HIV+ adults. The resultant “risk severity score” was used to differentially weight, as a function of age, the impact and magnitude of multiple risk factors on cognition. Among older adults (> 50 years) the risk severity index was differentially predictive of learning/memory and verbal fluency, whereas among younger adults it was linked to working memory and executive function. Cognitive reserve was found to be the most robust predictor of neurocognition.
doi:10.1080/13803395.2013.783000
PMCID: PMC3641576  PMID: 23547924
8.  A missing piece in the puzzle: HIV in mature adults in sub-Saharan Africa 
Future virology  2011;6(6):755-767.
Healthcare and social needs for mature adults aged 50 years or older differ from those of younger adults due to stigma concerning HIV in older people, beliefs that engagement in sexual activity no longer applies, age driven comorbidities and responses to antiretroviral treatment, which complicate HIV diagnosis and management. In the face of a growing HIV epidemic in mature adults, mostly due to infected people aging with HIV, but also due to new infections in this age group, HIV services, which mostly cater for HIV in young adults and children, and HIV education messages and interventions, which mainly target young adults, leave the mature adult exposed and vulnerable to HIV transmission and to a lack of care and treatment thereafter.
doi:10.2217/fvl.11.43
PMCID: PMC3303125  PMID: 22427781
ART; diagnosis; elderly; HIV; older adults; prevention
9.  Neuropsychiatric aspects of HIV infection among older adults 
Journal of clinical epidemiology  2001;54(Suppl 1):S44-S52.
Treatment advances such as the advent of highly active antiretroviral therapy (HAART) have translated into greater life expectancy for HIV-infected individuals, which will ultimately result in a “graying” of the HIV/AIDS epidemic. In addition, older individuals are engaging in a higher rate of high risk behaviors than had been previously expected. As such, study of older HIV-infected patients, including study of the psychiatric and neurocognitive aspects of the disease, appears highly indicated. Epidemiological studies have demonstrated that HIV infection is associated with higher rates of several psychological/psychiatric disorders when compared to general population base rates. There is also a rich literature that has documented the adverse neurocognitive effects of HIV infection, ranging from subtle cognitive complaints to frank dementia, among younger adults. Although it has been hypothesized that older age may potentiate the deleterious effects of HIV infection, little is actually known, however, regarding the incidence, prevalence, course, and clinical features of HIV-associated psychiatric and cognitive dysfunction among older adults. This article provides an overview of the epidemiology and clinical manifestations of HIV-associated cognitive and psychiatric disorder across the age spectrum, with particular focus on what is known regarding the interaction of advancing age and HIV infection. Future directions for research are suggested, including basic epidemiologic study of incidence and prevalence rates of neurodisease among older HIV-infected adults as well as investigations designed to determine whether the nature, severity, course, or treatment of such disorders differs among older versus younger patients.
PMCID: PMC2864032  PMID: 11750209
HIV infection; Older adults; Neuropsychiatric aspects
10.  The Semantic Relatedness of Cue-Intention Pairings Influences Event-Based Prospective Memory Failures in Older Adults with HIV Infection 
HIV infection and aging are each independently associated with prospective memory (ProM) impairment, which increases the risk of poor functional outcomes, including medication adherence. The incidence and prevalence of HIV infection among older adults has increased in recent years, thereby raising questions about the combined effects of these risk factors on ProM. In the present study, 118 participants were classified into four groups on the basis of HIV serostatus and age (i.e., ≤ 40 years and ≥ 50 years). Results showed significant additive effects of HIV and aging on event-based ProM, with the greatest deficits evident in the older HIV+ group, even after controlling for other demographic factors and potential medical, and psychiatric confounds. Event-based ProM impairment was particularly apparent in the older HIV+ group on trials for which the retrieval cue and intention were not semantically related. Worse performance on the semantically unrelated cue-intention trials was associated with executive dysfunction, older age, and histories of immunocompromise in the older HIV+ cohort. These data suggest that older HIV-infected adults are significantly less proficient at engaging the strategic encoding and retrieval processes required to a execute a future intention when the cue is unrelated to the intended action, perhaps secondary to greater neuropathological burden in the prefrontostriatal systems critical to optimal ProM functioning.
doi:10.1080/13803390903130737
PMCID: PMC2854853  PMID: 19763997
Human immunodeficiency virus; Episodic memory; aging; AIDS dementia complex; multi-process theory
11.  Successful cognitive aging in persons living with HIV infection 
Journal of Neurovirology  2010;17(1):110-119.
The number of older adults living with human immunodeficiency virus (HIV) infection is growing and this subpopulation of the epidemic is at heightened risk for a variety of poor health outcomes including HIV-associated neurocognitive disorders. The current study sought to examine the factors associated with freedom from neurocognitive impairment in older HIV-infected adults. Participants included 74 middle-aged and older (mean age 51 years), HIV-infected individuals with a mean estimated duration of infection of 17 years who underwent comprehensive neuropsychological, psychiatric, and medical evaluations. Successful cognitive aging (SCA) was operationally defined as the absence of neurocognitive deficits as determined by a battery of well-validated cognitive tests and self-endorsed cognitive complaints. Thirty-two percent of the cohort met these criteria. Compared to the group that did not meet these criteria, successful cognitive agers had significantly lower lifetime rates of major depressive disorder and current affective distress (e.g., depression, anxiety). Moreover, the SCA group evidenced better everyday functioning outcomes, including medication adherence, lower self-reported rates of declines in activities of daily living, and superior abilities related to medication management and dealing with healthcare providers. SCA was not related to demographic composition, HIV disease or treatment factors, medical comorbidities, or histories of substance use disorders. Findings from this preliminary study suggest that approximately one-third of older persons with HIV were free of cognitive impairments, which is associated with more favorable emotional, psychosocial, and everyday functioning.
doi:10.1007/s13365-010-0008-z
PMCID: PMC3032198  PMID: 21165783
Neuropsychological assessment; Aging; Treatment adherence; AIDS dementia; Depression
12.  Effects of traumatic brain injury on cognitive functioning and cerebral metabolites in HIV-infected individuals 
We explored the possible augmenting effect of traumatic brain injury (TBI) history on HIV (human immunodeficiency virus) associated neurocognitive complications. HIV-infected participants with self-reported history of definite TBI were compared to HIV patients without TBI history. Groups were equated for relevant demographic and HIV-associated characteristics. The TBI group evidenced significantly greater deficits in executive functioning and working memory. N-acetylaspartate, a putative marker of neuronal integrity, was significantly lower in the frontal gray matter and basal ganglia brain regions of the TBI group. Together, these results suggest an additional brain impact of TBI over that from HIV alone. One clinical implication is that HIV patients with TBI history may need to be monitored more closely for increased risk of HIV-associated neurocognitive disorder signs or symptoms.
doi:10.1080/13803395.2010.518140
PMCID: PMC3062232  PMID: 21229435
Head injury; HIV associated neurocognitive disorder; Neuropsychological performance; Magnetic resonance spectroscopy; N-acetylaspartate
13.  Aging, Neurocognition, and Medication Adherence in HIV Infection 
Objective
To evaluate the hypothesis that poor adherence to highly active antiretroviral treatment (HAART) would be more strongly related to cognitive impairment among older than among younger HIV-seropositive adults.
Setting and Participants
A volunteer sample of 431 HIV-infected adult patients prescribed self-administered HAART was recruited from community agencies and university-affiliated infectious disease clinics in the Los Angeles area.
Measurements
Neurocognitive measures included tests of attention, information processing speed, learning/memory, verbal fluency, motor functioning, and executive functioning. Medication adherence was measured using microchip-embedded pill bottle caps (Medication Event Monitoring System) and self-report. Latent/structural analysis techniques were used to evaluate factor models of cognition and adherence.
Results
Mean adherence rates were higher among older (≥50 years) than younger (<50 years) HIV-positive adults. However, latent/structural modeling demonstrated that neurocognitive impairment was associated with poorer medication adherence among older participants only. When cognitive subdomains were examined individually, executive functioning, motor functioning, and processing speed were most strongly related to adherence in this age group. CD4 count and drug problems were also more strongly associated with adherence among older than younger adults.
Conclusions
Older HIV-positive individuals with neurocognitive impairment or drug problems are at increased risk of suboptimal adherence to medication. Likewise, older adults may be especially vulnerable to immunological and neurocognitive dysfunction under conditions of suboptimal HAART adherence. These findings highlight the importance of optimizing medication adherence rates and evaluating neurocognition in the growing population of older HIV-infected patients.
doi:10.1097/JGP.0b013e31819431bd
PMCID: PMC2679810  PMID: 19307857
HIV; AIDS; aging; cognition; medication adherence; executive functions
14.  The Impact of Visual Distraction on Episodic Retrieval in Older Adults 
Brain research  2011;1430:78-85.
Impairment in long-term memory is one of the most salient alterations in cognitive aging. Findings of age-related deficits in source monitoring and recollection have revealed a selective decline in memory for detailed information. The underlying mechanism of this phenomenon is not well understood. We hypothesized that the influence of task-irrelevant visual stimuli present in our environment interferes with retrieval of detailed memories more for older than younger adults. We compared memory performance on a recall test for visual details when older adult participants’ eyes were closed versus performance when their eyes were open and irrelevant visual stimuli were presented. The results showed that the presence of irrelevant visual information diminished long-term memory performance based on an objective measure of recollection for visual details. Comparison of the current results to findings from our earlier study using the same experimental paradigm with younger adults revealed that visual distraction disrupted recollection of relevant details to a greater degree in older than younger adults. This result suggests that visual distraction overwhelms older adults’ declining cognitive control resources that are instrumental in the retrieval and selection of mnemonic details. More generally, these findings explicate a mechanistic basis for selective impairment of recollection in normal aging.
doi:10.1016/j.brainres.2011.10.048
PMCID: PMC3242871  PMID: 22119398
recollection; aging; interference; cognitive control
15.  Aging, Prospective Memory, and Health-Related Quality of Life in HIV Infection 
AIDS and behavior  2012;16(8):2309-2318.
HIV infection and older age are each independently associated with lower health-related quality of life (HRQoL) and deficits in prospective memory (PM), which is a distinct aspect of cognition involving the ability to “remember to remember” to do something at a future occasion. The present study investigated associations between PM and HRQoL in 72 older (≥ 50 years) and 41 younger (≤ 40 years) HIV-infected adults. Self-reported PM complaints predicted HRQoL across the entire sample, but there was a significant interaction between performance-based PM and age group on HRQoL, such that lower time-based PM was associated with lower HRQoL only in the younger cohort. Within the younger group, time-based and self-reported PM significantly predicted mental HRQoL independent of other risk factors (e.g., depression). These findings suggest that PM plays a unique role in HRQoL outcomes among younger persons living with HIV infection and support the examination of other age-related factors (e.g., effective use of compensatory strategies) that may regulate the adverse impact of PM on everyday functioning.
doi:10.1007/s10461-011-0121-x
PMCID: PMC3352996  PMID: 22246512
AIDS Dementia Complex; Aging; Prospective memory; Quality of life; Functional status; Health status
16.  Prepulse Inhibition in HIV-Associated Neurocognitive Disorders 
Sensorimotor inhibition, or the ability to filter out excessive or irrelevant information, theoretically supports a variety of higher-level cognitive functions. Impaired inhibition may be associated with increased impulsive and risky behavior in everyday life. Individuals infected with HIV frequently show impairment on tests of neurocognitive function, but sensorimotor inhibition in this population has not been studied and may be a contributor to the profile of HIV-associated Neurocognitive Disorders (HAND). 37 HIV-infected individuals (15 with HAND) and 48 non-infected comparison subjects were assessed for prepulse inhibition (PPI), an eyeblink startle paradigm measuring sensorimotor gating. Although HIV status alone was not associated with PPI deficits, HIV-positive participants meeting criteria for HAND showed impaired PPI compared to cognitively intact HIV-positive subjects. In HIV-positive subjects, PPI was correlated with working memory but was not associated with antiretroviral therapy or illness factors. In conclusion, sensorimotor disinhibition in HIV accompanies deficits in higher-order cognitive functions, though the causal direction of this relationship requires investigation. Subsequent research on the role of sensorimotor gating on decision-making and risk behaviors in HIV may be indicated.
doi:10.1017/S1355617713000301
PMCID: PMC3729041  PMID: 23552464
sensorimotor gating; AIDS dementia complex; cognition; startle; working memory; impulsivity
17.  Rule-Based Category Learning in Children: The Role of Age and Executive Functioning 
PLoS ONE  2014;9(1):e85316.
Rule-based category learning was examined in 4–11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working memory and inhibitory control were related to rule-based categorization and improved with age, working memory specifically was found to marginally mediate the age-related improvements in categorization. When analyses focused only on the sample of children, results showed that working memory ability and inhibitory control were associated with categorization performance and strategy use. The current findings track changes in categorization performance across childhood, demonstrating at which points performance begins to mature and resemble that of adults. Additionally, findings highlight the potential role that working memory and inhibitory control may play in rule-based category learning.
doi:10.1371/journal.pone.0085316
PMCID: PMC3906381  PMID: 24489658
18.  Does Differential Strategy Use Account for Age-Related Deficits in Working-Memory Performance? 
Psychology and aging  2009;24(1):82-92.
The strategy-deficit hypothesis states that age differences in the use of effective strategies contribute to the age-related deficits in working memory (WM) span performance. To evaluate this hypothesis, strategy use was measured using set-by-set strategy reports during the reading span (RSPAN) task (Experiments 1 and 2) and the operation span (OSPAN) task (Experiment 2). Individual differences in the reported use of effective strategies accounted for substantial variance in span performance. In contrast to the strategy-deficit hypothesis, however, young and older adults reported using the same proportion of normatively effective strategies on both span tasks. Measures of processing speed accounted for a substantial proportion of the age-related variance in span performance. Thus, although using normatively effective strategies accounts for individual differences in span performance, age differences in effective strategy use cannot explain the age-related variance in that performance.
doi:10.1037/a0014078
PMCID: PMC2658624  PMID: 19290740
19.  Intraindividual Variability in HIV Infection: Evidence for Greater Neurocognitive Dispersion in Older HIV Seropositive Adults 
Neuropsychology  2011;25(5):645-654.
Objective
Both the prevalence and incidence of HIV infection among older adults are on the rise. Older adults are at increased risk of HIV-associated neurocognitive disorders, which has historically been characterized as an inconsistent or “spotty” pattern of deficits. Dispersion is a form of intraindividual variability (IIV) that is defined as within-person variability in performance across domains and has been associated with poorer neurocognitive functioning and incipient decline among healthy older adults. To our knowledge, no studies have yet examined dispersion in an aging HIV-infected sample.
Methods
For the current study we examined the hypothesis that age and HIV infection have synergistic effects on dispersion across a battery of clinical and experimental cognitive tasks. Our well-characterized sample comprised 126 HIV-seropositive individuals (HIV+) and 40 HIV-seronegative comparison individuals (HIV−), all of whom were administered a comprehensive neuropsychological battery.
Results
Consistent with our hypothesis, an age by HIV serostatus interaction was observed, with the older HIV+ group demonstrating a higher level of dispersion relative to older HIV− and younger HIV+ individuals, even when potentially confounding demographic and medical factors were controlled.
Conclusion
Our results demonstrate that older HIV+ adults produce greater dispersion, or intraindividual variability in performance across a range of tests, which may be reflective of cognitive dyscontrol to which this population is vulnerable, perhaps driven by the combined effects of aging and HIV infection on prefrontostriatal systems.
doi:10.1037/a0023792
PMCID: PMC3158302  PMID: 21574712
HIV; aging; neuropsychological assessment; variability
20.  Age-related impairments in active learning and strategic visual exploration 
Old age could impair memory by disrupting learning strategies used by younger individuals. We tested this possibility by manipulating the ability to use visual-exploration strategies during learning. Subjects controlled visual exploration during active learning, thus permitting the use of strategies, whereas strategies were limited during passive learning via predetermined exploration patterns. Performance on tests of object recognition and object-location recall was matched for younger and older subjects for objects studied passively, when learning strategies were restricted. Active learning improved object recognition similarly for younger and older subjects. However, active learning improved object-location recall for younger subjects, but not older subjects. Exploration patterns were used to identify a learning strategy involving repeat viewing. Older subjects used this strategy less frequently and it provided less memory benefit compared to younger subjects. In previous experiments, we linked hippocampal-prefrontal co-activation to improvements in object-location recall from active learning and to the exploration strategy. Collectively, these findings suggest that age-related memory problems result partly from impaired strategies during learning, potentially due to reduced hippocampal-prefrontal co-engagement.
doi:10.3389/fnagi.2014.00019
PMCID: PMC3924049  PMID: 24592236
active learning; memory; aging; age-related memory impairment; vicarious trial-and-error behavior; hippocampus; prefrontal cortex; revisitation
21.  An expectation-based memory deficit in aging 
Neuropsychologia  2011;49(6):1466-1475.
Memory performance can be enhanced by expectations regarding the appearance of ensuing stimuli. Here, we investigated the influence of stimulus-category expectation on memory performance in aging, and used fMRI to explore age-related alterations in associated neural mechanisms. Unlike younger adults, who demonstrated both working memory (WM) and long-term memory (LTM) performance benefits for face stimuli when this stimulus category was expected, older adults did not exhibit these memory benefits. Concordantly, older adults did not exhibit expectation-period activity modulation in visual association cortex (i.e., fusiform face area (FFA)). However, within the older population, individuals who demonstrated face-expectation memory benefits also exhibited expectation-period FFA activity modulation equivalent to younger adults. The older cohort also displayed diminished expectation-related functional connectivity between regions of the prefrontal cortex and the FFA, relative to younger adults, suggesting that network alterations underlie the absence of expectation-mediated cortical modulation and memory benefits. This deficit may have broader consequences for the effective utilization of predictive cues to guide attention and engender optimal cognitive performance in older individuals.
doi:10.1016/j.neuropsychologia.2010.12.021
PMCID: PMC3095697  PMID: 21272595
Memory; Attention; Expectation; Aging; fMRI; Functional Connectivity
22.  A review of cardiovascular and renal function monitoring: a consideration of older adults with HIV 
HIV/AIDS (Auckland, N.Z.)  2013;5:263-274.
The prevalence of human immunodeficiency virus (HIV) infection in older and elderly adults is significant worldwide. This population poses new challenges and opportunities in the management of HIV. In addition to the risks affecting HIV patients of all ages, including risk of opportunistic infection and medication resistance, age-related changes in physiology, higher comorbidity burdens, increased use of medications, and potential adverse drug reactions to HIV medications all factor into the care of older adults with HIV. The risk and progression of cardiovascular and renal comorbidities may be higher in the older adult HIV population and in patients taking specific HIV medications. Understanding these risks is essential when managing a new type of patient: the older adult with HIV.
doi:10.2147/HIV.S36311
PMCID: PMC3782510  PMID: 24068878
older adult; elderly; geriatrics; cardiovascular disease; kidney disease; renal dysfunction; HIV
23.  Working and Episodic Memory in HIV Infection, Alcoholism, and Their Comorbidity: Baseline and 1-Year Follow-Up Examinations 
Background
Selective memory deficits occur in individuals with human immunodeficiency virus (HIV) infection and those with chronic alcoholism, but the potential compounded effect of these conditions is seldom considered, despite the high prevalence of alcohol use disorders in HIV infection.
Methods:
Here, we examined component processes of working and episodic memory in HIV infection and chronic alcoholism (ALC) in 4 subject groups (HIV, ALC, HIV + ALC, and normal controls) at baseline and 1-year follow-up. Accuracy scores, response times, and rate of information processing were assessed with subtests of the computerized neuropsychological test battery, the MicroCog.
Results:
Although individuals with either HIV infection or alcoholism generally performed at normal levels, individuals comorbid with HIV infection and alcoholism were impaired relative to controls and to the single diagnosis groups on selective memory processes. Immediate episodic memory was impaired, whereas working memory remained intact. Ability to retain information over time was not impaired in the clinical groups. Little performance change between groups was detected over 1 year. Results could not be explained by amount of alcohol consumed over a lifetime, CD4 cell count, AIDS diagnosis, or HAART medication.
Conclusions:
This study provides behavioral support for adverse synergism of HIV infection and chronic alcoholism on brain function and is consistent with neuroimaging reports of compromised hippocampal and associated memory structures related to episodic memory processes in these 2 conditions.
doi:10.1111/j.1530-0277.2009.01020.x
PMCID: PMC2832705  PMID: 19656122
HIV Infection; Alcoholism; Comorbidity; Memory; MicroCog
24.  Comparison of scales to evaluate the progression of HIV-associated neurocognitive disorder 
HIV therapy  2010;4(3):371-379.
Aim
First, to compare the characterization of neurocognitive deficits in milder stages of HIV-associated neurocognitive disorder (HAND) derived from existing dementia rating scales of the American Academy of Neurology (AAN) and Memorial Sloan Kettering (MSK) with the 2007 consensus (‘Frascati’) classification. Second, to identify potential sociodemographic and clinical predictors of HAND progression during 1-year follow-up.
Methods
104 HIV-infected subjects in an existing cohort system were evaluated with a medical history, exam, neuropsychological test battery and functional assessments. The degree of HAND was rated using the AAN, MSK and Frascati scales. The degree of concordance among these scales was determined. In addition, 45 subjects were reassessed for changes in their neurocognitive status at 1-year follow-up. Associations between age, education, sex, depression ratings, substance abuse, race, hepatitis C serostatus, CD4 count and progression of HAND were examined.
Results
There was excellent concordance (γ > 0.8) among the Frascati, MSK and AAN ratings. Subjects rated as having minor cognitive motor disorder on the AAN scale (n = 45) were evenly split between Frascati rating of asymptomatic neurocognitive impairment (n = 24) and mild neurocognitive disorder (n = 21). At 1-year follow-up of 45 subjects, 31% had worsened, 13% had improved and 56% were stable. Predictors of progression included age older than 50 years (odds ratio: 5.57; p = 0.013) and female gender (odds ratio: 3.13; p = 0.036).
Conclusion
The Frascati HAND rating scale has excellent concordance with previous neurocognitive rating scales and can be used to better characterize milder stages of cognitive impairment. Older individuals and women appeared to be more likely to show neurocognitive progression.
doi:10.2217/hiv.10.23
PMCID: PMC2933171  PMID: 20824119
dementia rating scales; Frascati; HIV; HIV-associated neurocognitive disorders; progression
25.  Epidemiology of HIV and response to antiretroviral therapy in the middle aged and elderly 
Aging health  2008;4(6):615-627.
HIV is increasing in prevalence in the middle aged and older population owing to both increased longevity, and new infections in these populations. Highly active antiretrorival therapy (HAART) therapy may be less effective at restoring immune function in older patients compared with younger patients. There are significant toxicities associated with HAART therapy that, combined with decreased renal and liver function in older patients, may be more problematic in older HIV-infected patients. Comorbid disease is becoming an increasing problem with coadministration of multiple drugs and significant drug–drug interactions. Psychosocial issues in the older patient are often different than those in younger HIV-infected patients and providers should try to address these issues early. Finally, future research should work to identify the ideal timing and type of HAART regimens for older HIV-infected individuals.
doi:10.2217/1745509X.4.6.615
PMCID: PMC2776752  PMID: 19915688
age; aging; antiretroviral therapy; elderly; HIV; mortality

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