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Diabetes and cIMT Linked to Worse Neurocognitive Performance With HIV
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
"metabolic factors .......play a relevant role in the pathogenesis of HIV-associated neurocognitive disorders." The protective impact of abacavir, the researchers proposed, could reflect the good central nervous system penetration of this nucleoside.Ó From Jules: in the medical literature it is well recognized that metabolic disorders like CVD, diabetes, insulin resistance, abnormal lipids, hypertension etc can all play a role in contributing to neurologic dysfunction, cognitive impairment
Mark Mascolini
Diabetes and greater carotid artery intima media thickness (cIMT) correlated with worse neurocognitive performance in a cross-sectional study of 247 people with HIV [1]. Abacavir protected people against low neurocognitive scores. The findings reflect results of a published SMART trial analysis [2].
Metabolic disorders, cardiovascular disease, and neurocognitive deficits persist as problems in people responding to antiretroviral therapy. But possible associations between these conditions remain still poorly understood. To address this issue, clinicians at two HIV centers in Rome enrolled 247 consecutive outpatients in a cross-sectional study. They excluded anyone younger than 18 and anyone with central nervous system opportunistic infections or other neurologic disorders, active psychiatric disorders, or alcohol or drug abuse.
Study participants were evaluated for depression (on the Zung Depression Scale) and underwent comprehensive neuropsychological testing including assessment of memory, attention, executive abilities, and fine motor skills. Performance was rated "pathological" if a person scored below the age- and education-adjusted normative cutoff. At the time of neuropsychological testing, study participants also underwent ultrasonography to determine cIMT 1 centimeter from the carotid bulb. If the averaged value of three measurements on the left or right side was 0.9 mm or greater, the result was considered abnormal.
Three quarters of the study group were men, median age was 46 years (interquartile range [IQR] 39 to 52), and median education level was 11 years (IQR 8 to 13). Fifty-four people (22%) had injected drugs. Median CD4 count stood at 527 (IQR 388 to 717), and 208 people (84%) had a viral load under 50 copies. Twenty-nine people (12%) had a pathological Zung depression score (above 49).
Only 17% of study participants reported no cardiovascular risk factor, while 83% had one risk factor and 44% had two. The most prevalent cardiovascular risk factors were current smoking in 53%, abnormal lipids in 25%, hypertension in 15%, and family history of cardiovascular disease in 13%. cIMT stood at or above 0.9 mm in 79 people (32%).
Neuropsychological testing showed that 101 people (41%) had mild neurocognitive impairment (3 or more pathological tests). The study group had a median of 2 pathological tests (IQR 1 to 4).
Multivariate analysis identified four independent predictors of neurocognitive performance, measured as average change in pathological test results (and 95% confidence interval). Negative values indicate a protective association.
-- Education (per 1 year increase): -0.23 (-0.31 to -0.15), P < 0.001
-- Current abacavir: -0.97 (-1.73 to -0.21), P = 0.013
-- Diabetes: +1.27 (+0.06 to +2.48), P = 0.040
-- cIMT >/= 0.9 mm: +0.70 (+0.03 to +1.37), P = 0.041
The independent associations between diabetes, cIMT, and poor neurocognitive performance suggested to the investigators that "metabolic factors could play a relevant role in the pathogenesis of HIV-associated neurocognitive disorders." The protective impact of abacavir, the researchers proposed, could reflect the good central nervous system penetration of this nucleoside.
The results add to findings in a recent SMART study analysis [2]. This assessment of 292 SMART participants in Australia, North America, Brazil, and Thailand found that high cholesterol, hypertension, and prior cardiovascular disease were associated with poor neurocognitive performance. In the same analysis, conventional risk factors for HIV-associated dementia and antiretroviral central nervous system penetration effectiveness score did not correlate with neurocognitive performance.
References
1. Fabbiani M, Ciccarelli N, Silver MC, et al. CV risk factors and carotid IMT are correlated to lower neurocognitive performance in HIV-infected patients. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 403.
2. Wright EJ, Grund B, Robertson K, et al. Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons. Neurology. 2010;75:864-873.
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