Mark L. Ettenhofer

Executive Functions and ADHD in Adults: Evidence for Selective Effects on ADHD Symptom Domains

Dual-process models of attention-deficit/hyperactivity disorder (ADHD) suggest that both executive functioning and regulatory functions (e.g., processing speed) are involved and that executive function weaknesses may be associated specifically with symptoms of inattention-disorganization but not hyperactivity-impulsivity. Adults aged 18-37 (105 with ADHD, 90 controls) completed a neuropsychological battery. The ADHD group had weaker performance than did the control group (p<.01) on both executive and speed measures. Symptoms of inattention-disorganization were uniquely related to executive functioning with hyperactivity-impulsivity controlled. Inattention was associated with slower response speed, and hyperactivity-impulsivity with faster output speed. Results were not accounted for by IQ, age, gender, education level, or comorbid disorders. Findings are discussed in terms of developmental and dual-process models of ADHD leading into adulthood.

Functional Consequences of HIV-Associated Neuropsychological Impairment

This review focuses on the “real world” implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.

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 (>or=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.

Executive functions and adaptive functioning in young adult attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in occupational, social, and educational functioning in adults. This study examined relations of adaptive impairment to ADHD symptom domains (inattentive-disorganized and hyperactive-impulsive) and to deficits in executive functioning (EF) in 195 well-characterized adults (105 ADHD, 90 non-ADHD, between ages 18 and 37). Participants completed a battery of EF measures as well as assessments of adaptive functioning. Confirmatory factor analyses were used to validate latent factors for adaptive functioning and EF. In a measurement model, weaker EF was associated with poorer adaptive functioning (r = -.30). When multi-informant composite variables for current inattentive-disorganized and hyperactive-impulsive ADHD symptoms were included in the structural model, EF no longer predicted adaptive functioning. While both symptom composites were similarly related to EF (inattentive-disorganized r = .36; hyperactive-impulsive r = .29), inattentive-disorganized symptoms accounted for more variance in adaptive functioning (67.2% vs. 3.6%). Furthermore, for retrospectively reported childhood symptoms of ADHD, only the inattentive-disorganized symptom domain was related to EF or adaptive impairment. These results suggest that, in adults with ADHD, inattentive-disorganized symptoms may be the primary contributor to key aspects of poorer adaptive function and may be the behavioral path through which EF deficits lead to adaptive impairment.

Reciprocal prediction of medication adherence and neurocognition in HIV/AIDS

Background: Antiretroviral medications have been shown to benefit neurocognition in HIV/AIDS, and neurocognitive deficits are a risk factor for poor adherence to these medications. However, little is known about the predictive pathways linking medication adherence with cognitive ability. Methods: In the current 6-month cohort study, antiretroviral medication adherence was tracked prospectively among 91 HIV-positive adults using electronic monitoring. Comprehensive neuropsychological evaluations were performed at baseline and 6 months. Results: Multivariate path analyses provided evidence that antiretroviral adherence and cognitive ability are reciprocally related, although the neurocognitive pathways of this relationship appear to vary by predictive direction. Executive function and learning/memory were most strongly predictive of levels of medication adherence achieved, whereas higher levels of adherence were predictive of relative improvements in a wide range of frontostriatal brain functions including processing speed, attention, executive functions, and motor functioning. Conclusions: These data provide evidence that cognition and adherence are reciprocally related in HIV/AIDS. In particular, executive dysfunction may play a key role in this relationship. Interventions aimed at improving or preserving executive functions could hold promise for interrupting progressive declines in adherence and neurocognitive ability in HIV/AIDS.

Neurocognitive functioning in HIV-1 infection: effects of cerebrovascular risk factors and age

This study examined the interactive effects of cerebrovascular risks, advancing age, and HIV infection on neurocognition, and explored whether pharmacological treatment of cerebrovascular risk factors attenuated neurocognitive dysfunction. Participants included 98 HIV-seropositive adults (cerebrovascular risk: 23.5%; age > 50: 27.6%). Cerebrovascular risk was associated with slower processing speed even after controlling for age effects (b = −2.071; p =.04), and the interaction of age and cerebrovascular risk was associated with poorer verbal fluency (b = 1.276, p =.002). Participants with pharmacologically untreated cerebrovascular risk demonstrated reduced processing speed, learning/memory, and executive functioning relative to those on medication. Poor cerebrovascular health confers significant risk for HIV+ individuals, and this effect may be of greater consequence than advancing age. The cognitive impact of risk appears to be more pronounced in the absence of adequate pharmacological treatment.

Reliability and stability of executive functioning in older adults.

A number of methodological questions have been raised about the reliability and validity of measuring executive functioning (EF) across multiple time points. In this study, correlational and latent-variable analyses were used to examine test-retest reliability of 5 common measures of EF and the stability of a latent EF construct. One hundred eighteen nondemented older adults were tested twice over a 4- to 8-week period. Findings demonstrated modest reliability of individual EF measures but very high stability of a latent EF construct. Relative contributions of each measure to the latent EF factor did not change across measurement trials. In addition, age-related effects on EF were similar at the 2 time points and were within the expected range. Implications for future studies of EF are discussed.

Cognitive Reserve as a Protective Factor in Older HIV-Positive Patients at Risk for Cognitive Decline

The present study examined the impact of cognitive reserve in maintaining intact neuropsychological (NP) function among older HIV-positive individuals, a uniquely at-risk subgroup. Participants included 129 individuals classified by HIV serostatus, age group, and NP impairment. A three-way analysis of variance (ANOVA) followed by a series of within-group ANOVA and multiple regression analyses were conducted to investigate the pattern of cognitive reserve (vs. other protective) influence among groups with varying risks of NP impairment. Results indicated a significant age × HIV status interaction, with older HIV-positive individuals demonstrating higher cognitive reserve than subgroups with less risk for NP compromise (younger age and/or HIV-negative). Results demonstrated higher cognitive reserve specific to NP-intact older HIV-positive individuals. Within this group, the interaction of younger age and higher cognitive reserve independently contributed to cognitive status when controlling for psychiatric, immunological, and psychosocial protective mechanisms, suggesting the importance of cognitive reserve beyond other protective mechanisms in maintaining optimal NP functioning in those individuals most at risk. Alongside younger age, factors contributing to cognitive reserve (i.e., education and estimated premorbid intelligence) may provide substantial benefit for older HIV-positive adults who are at high risk for NP compromise.

Cerebral metabolism, cognition, and functional abilities in Alzheimer disease.

Patients with Alzheimer disease (AD) exhibit profound difficulties in completing instrumental activities of daily living (IADLs), such as managing finances, organizing medications, and food preparation. It is unclear which brain areas underlie IADL deficits in AD. To address this question, we used voxel-based analysis to correlate the performance of IADLs with resting cerebral metabolism as measured during [18F] fluorodeoxyglucose–positron emission tomography (FDG-PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was associated with hypometabolism in right-sided cortical regions, including the parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and frontal pole. Follow-up path analyses examining anatomically defined regions of interest (ROI) demonstrated that the association between metabolism and IADLs was mediated by global cognition in frontal ROIs, and partially mediated by global cognition in the parietal ROI. Findings suggest that hypometabolism of right sided brain regions involved in executive functioning, visuospatial processing, attention, and working memory underlie functional impairments in patients with AD.

Visuospatial and Attentional Abilities Predict Driving Simulator Performance Among Older HIV-infected Adults

Objectives: To examine the effects of aging and neuropsychological (NP) impairment on driving simulator performance within a human immunodeficiency virus (HIV)-infected cohort. Methods: Participants included 79 HIV-infected adults (n = 58 > age 50, n = 21 ≤ 40) who completed a NP battery and a personnel computer-based driving simulator task. Outcome variables included total completion time (time) and number of city blocks to complete the task (blocks). Results: Compared to the younger group, the older group was less efficient in their route finding (blocks over optimum: 25.9 [20.1] vs 14.4 [16.9]; P = .02) and took longer to complete the task (time: 1297.6 [577.6] vs 804.4 [458.5] seconds; P = .001). Regression models within the older adult group indicated that visuospatial abilities (blocks: b = −0.40, P <.001; time: b = −0.40, P = .001) and attention (blocks: b = −0.49, P = .001; time: b = −0.42, P = .006) independently predicted simulator performance. The NP-impaired group performed more poorly on both time and blocks, compared to the NP normal group. Conclusions: Older HIV-infected adults may be at risk of driving-related functional compromise secondary to HIV-associated neurocognitive decline.