Matthew J. Wright

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.

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.

Verbal memory impairment in severe closed head injury: The role of encoding and consolidation

We applied the item-specific deficit approach (ISDA) to California Verbal Learning Test data obtained from 56 severe, acceleration–deceleration closed head injury (CHI) participants and 62 controls. The CHI group demonstrated deficits on all ISDA indices in comparison to controls. Regression analyses indicated that encoding deficits, followed by consolidation deficits, accounted for most of the variance in delayed recall. Additionally, level of acquisition played a partial role in CHI-associated consolidation difficulties. Finally, CHI encoding deficits were largely driven by low semantic clustering during list learning. These results suggest that encoding (primary) and consolidation (secondary) deficits account for CHI-associated verbal memory impairment.

Basal ganglia structures differentially contribute to verbal fluency: Evidence from Human Immunodeficiency Virus (HIV)-infected adults

BACKGROUND The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to lexico-semantic verbal fluency performance among older HIV infected adults. METHOD 20 older (50+ years) HIV+ adults underwent MRI and were administered measures of semantic and phonemic fluency. BG (caudate, putamen) regions of interest were extracted. RESULTS Performance on phonemic word generation significantly predicted caudate volume, whereas performance on phonemic switching predicted putamen volume. CONCLUSIONS These findings suggest a double dissociation of BG involvement in verbal fluency tasks with the caudate subserving word generation and the putamen associated with switching. As such, verbal fluency tasks appear to be selective to BG function.

The Item-Specific Deficit Approach to evaluating verbal memory dysfunction: Rationale, psychometrics, and application

In the current study, we introduce the Item-Specific Deficit Approach (ISDA), a novel method for characterizing memory process deficits in list-learning data. To meet this objective, we applied the ISDA to California Verbal Learning Test (CVLT) data collected from a sample of 132 participants (53 healthy participants and 79 neurologically compromised participants). Overall, the ISDA indices measuring encoding, consolidation, and retrieval deficits demonstrated advantages over some traditional indices and indicated acceptable reliability and validity. Currently, the ISDA is intended for experimental use, although further research may support its utility for characterizing memory impairments in clinical assessments.

Comparison of Credible Patients of Very Low Intelligence and Non-Credible Patients on Neurocognitive Performance Validity Indicators

The purpose of this archival study was to identify performance validity tests (PVTs) and standard IQ and neurocognitive test scores, which singly or in combination, differentiate credible patients of low IQ (FSIQ ≤ 75; n = 55) from non-credible patients. We compared the credible participants against a sample of 74 non-credible patients who appeared to have been attempting to feign low intelligence specifically (FSIQ ≤ 75), as well as a larger non-credible sample (n = 383) unselected for IQ. The entire non-credible group scored significantly higher than the credible participants on measures of verbal crystallized intelligence/semantic memory and manipulation of overlearned information, while the credible group performed significantly better on many processing speed and memory tests. Additionally, credible women showed faster finger-tapping speeds than non-credible women. The credible group also scored significantly higher than the non-credible subgroup with low IQ scores on measures of attention, visual perceptual/spatial tasks, processing speed, verbal learning/list learning, and visual memory, and credible women continued to outperform non-credible women on finger tapping. When cut-offs were selected to maintain approximately 90% specificity in the credible group, sensitivity rates were highest for verbal and visual memory measures (i.e., TOMM trials 1 and 2; Warrington Words correct and time; Rey Word Recognition Test total; RAVLT Effort Equation, Trial 5, total across learning trials, short delay, recognition, and RAVLT/RO discriminant function; and Digit Symbol recognition), followed by select attentional PVT scores (i.e., b Test omissions and time to recite four digits forward). When failure rates were tabulated across seven most sensitive scores, a cut-off of ≥ 2 failures was associated with 85.4% specificity and 85.7% sensitivity, while a cut-off of ≥ 3 failures resulted in 95.1% specificity and 66.0% sensitivity. Results are discussed in light of extant literature and directions for future research.

Cross Validation of the b Test in a Large Known Groups Sample

The b Test (Boone, Lu, & Herzberg, 2002a) is a measure of cognitive performance validity originally validated on 91 non-credible participants and 7 credible clinical comparison groups (total n = 161). The purpose of the current study was to provide cross-validation data for the b Test on a known groups sample of non-credible participants (n = 212) and credible heterogeneous neuropsychological clinic patients (n = 103). The new data showed that while the original E-score cut-off of ≥155 achieved excellent specificity (99%), it was associated with relatively poor sensitivity (41%). However, the cut-off could be substantially lowered to ≥82, while still maintaining adequate specificity (≥90%) and raising sensitivity to 68%. Examination of non-credible subgroups revealed that b Test sensitivity in feigned mild traumatic brain injury (mTBI) was 58%, whereas in non-credible patients claiming depression and psychosis, cut-off sensitivity was 76% and 67%, respectively. These data suggest that the b Test may have a particular role in detection of non-credible cognitive symptoms associated with feigned psychiatric symptoms, and that fabricated deficits in processing speed and vigilance/visual scanning, detected by the b Test, are more prominent in feigned psychiatric presentations than in feigned mTBI. Further, b Test failures in patients with somatoform disorders were common, indicating that the b Test may have a specific use in detection of non-consciously created cognitive dysfunction associated with somatoform conditions.

Antiretroviral Adherence and the Nature of HIV-Associated Verbal Memory Impairment

The authors investigated the relationship between antiretroviral adherence and HIV-associated verbal memory impairment. HIV-positive participants demonstrated poorer verbal memory than HIV-negative participants. Both good (≥90%) and poor (<90%) adherers displayed encoding deficits as compared with controls, but only poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted for reduced delayed recall in good adherers, but both encoding and retrieval deficits accounted for reduced delayed recall in poor adherers. The retrieval difference between the adherence groups might be explained by a neuroprotective effect of good antiretroviral adherence or preexisting HIV-related retrieval deficits that result in poorer adherence.

Operationalization of the updated diagnostic algorithm for classifying HIV-related cognitive impairment and dementia.

BACKGROUND This study applies the updated HIV-Associated Neurocognitive Disorders (HAND) diagnostic algorithm. METHODS Participants were 210 HIV-infected-adults, classified using proposed HAND criteria: HIV-Associated Dementia (HAD), Mild Neurocognitive Disorder (MND), Asymptomatic Neurocognitive Impairment (ANI). RESULTS The algorithm yielded: normal = 32.8%, ANI = 21.4%, MND = 34.3%, and HAD = 11.4%. Normal participants performed superior to HAND-defined participants on cognition, and HAD participants performed more poorly on global cognition and executive functioning. Two distinct subgroups of interest emerged: (1) functional decline without cognitive impairment; (2) severe cognitive impairment and minimal functional compromise. CONCLUSIONS The algorithm discriminates between HIV-infected cognitively impaired individuals. Diagnosis yields two unique profiles requiring further investigation. Findings largely support the algorithms utility for diagnosing HIV-cognitive-impairment, but suggest distinct subsets of individuals with discrepant cognitive/functional performances that may not be readily apparent by conventional application of HAND diagnosis.

Content Memory and Temporal Order Memory for Performed Activities After Severe Closed-Head Injury

Thirty severe closed-head injured (CHI) participants (more than 1 year postinjury) and 30 matched controls completed eight different cognitive activities. Participants’ free recall and recognition of the activities provided a measure of content memory. Temporal order memory was assessed with a reconstruction task. CHI participants recalled and recognized fewer activities than did controls. However, the CHI and control groups did not differ in temporal order memory. For both groups, recognition memory was not correlated with temporal order memory. These results demonstrate intact temporal order memory for performed activities in a severe CHI population, and support the notion of separate processing of content memory and order information. Issues related to automaticity and the roles of the frontal lobes in temporal order memory are also discussed.