HIV-associated neurocognitive disorder in Australia: a case of a high-functioning and optimally treated cohort and implications for international neuroHIV research.

The Australian HIV-infected (HIV+) population is largely comprised of high-functioning men who have sex with men (MSM). Like other English-speaking countries, Australia mostly relies on US neuropsychological normative standards to detect and determine the prevalence of neurological disorders. Whether the US neuropsychological (NP) normative standards are appropriate in Australian HIV+ MSM has not been established. Ninety virally suppressed HIV+ and 49 HIV-uninfected (HIV-) men (respectively 86 and 85 % self-reported MSM; mean age 54 and 56 years, mean premorbid verbal IQ estimate 110 and 111) undertook standard NP testing. The raw neuropsychological data were transformed using the following: (1) US standards as uncorrected scaled scores and demographically corrected T scores (US norms); and (2) z scores (without demographic corrections) derived from Australian comparison group scaled scores (local norms). To determine HIV-associated neurocognitive disorder prevalence, we used a standard definition of impairment based upon a battery-wide summary score: the global deficit score (GDS). Impairment classification (GDS ≥ 0.5) based on the local norms was best at discriminating between the two groups (HIV- = 14.3 % vs. HIV+ = 53.3 %; p < 0.0001). This definition was significantly associated with age. Impairment classification based on the US norms yielded much lower impairment rate regardless of the HIV status (HIV- = 4.1 % vs. HIV+ = 14.7 %; p = 0.05), but was associated with historical AIDS, and not age. Both types of summary scores were associated with reduced independence in activities of daily living (p ≤ 0.03). Accurate neuropsychological classifications of high (or low) functioning individuals may need country-specific norms that correct for performance-based (e.g., reading) estimates of premorbid cognition in addition to the traditional demographic factors.

HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study.

BACKGROUND: Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear. METHODS: 92 HIV- infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV-) subjects underwent (1)H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals. RESULTS: Relative to HIV- individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (p<.04) and higher myo-inositol (mIo) (p<.04); in the caudate: lower NAA (p = .01); and in the posterior cingulate cortex: higher mIo (p<.008- also significant when Holm-Sidak corrected) and higher Choline/NAA (p<.04). Regression models showed that an HIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter. CONCLUSIONS: In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by chronic inflammation.

Facial emotional processing in HIV infection: relation to neurocognitive and neuropsychiatric status.

OBJECTIVE: To examine facial emotional processing in HIV+ individuals and its relation to neurocognitive performance, neuropsychiatric symptomatology and immune status. METHOD: Participants included 85 HIV+ individuals (83 males, 2 females) and 25 age-comparable HIV- individuals (22 males, 3 females). Participants underwent The University of Pennsylvania computerized neuropsychological facial emotion test battery, standardized neuropsychological testing, neurobehavioral questionnaires, a semistructured psychiatric interview, and an assessment of independence in activities of daily living. RESULTS: Relative to HIV- controls, HIV+ individuals showed a mild difference for recognition of sadness (p = .02, d = 0.43), discrimination of happiness (p = .02, d = 0.52), and speed of recognition for fear (p = .04, d = 0.37). HIV+ individuals with HIV-associated neurocognitive disorder (HAND; 20%) had abnormal emotional facial recognition (p = .04; d = .59), and slower recognition of negative facial expressions (p < .01; d = .63-.83), as well as poorer discrimination of happy facial expressions (p < .003, d = .83). Apathy, depression, reduced independence in activities of daily living, and HIV biomarkers were not associated with reduced facial emotion recognition in the HIV+ group. CONCLUSIONS: Clinically stable HIV+ individuals show a mild level of emotional processing reduction that is dissociated from neuropsychiatric complaints. Individuals with HAND showed moderate to large emotional processing abnormalities, particularly for the timely recognition of negative expressions (fear, sadness, and anger). These findings warrant a more comprehensive and dynamic evaluation of emotional processing in HIV infection and an investigation of the integrity of the fronto-basal-amygdala circuits.