| Authors: Heaton R, Franklin D, Woods S, Marra C, Clifford D,
Gelman B, McArthur J, Morgello S, McCutchan A, and Grant I |
| Abstract:Background: Although HIV-associated neurocognitive disorders (HAND) remain prevalent
despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic
neurocognitive impairment (ANI) (the most common HAND diagnosis) remains unclear. This
study investigated neurocognitive decline over 18 to 42 months in a group of HIV-infected
individuals with and without HAND.
Methods: 387 CHARTER participants with 18 to 42 months of follow-up (mean (SD) = 36.1
(10.0)) were selected based on being neuropsychologically normal (NP-N; n=246) or having ANI
(n=84) or mild neurocognitive disorder (symptomatic NP impairment; MND; n=57) based on
established criteria. Participants were assessed every 6 months and published, regressionbased
norms for change were used to generate an average summary change score across
visits. Groups were compared (t-test) on average summary change score and overall change
status (decline, stable, improve; chi-square) at the last study visit.
Results: The groups did not differ on duration of follow-up or on HIV disease or treatment
characteristics at baseline, but the ANI group was more educated than the other two groups
(p<.0001) and more of the MND group were women (p=.006) and ethnic minorities (p=.02), and
had lower estimates of premorbid intelligence (reading score, p=.003) than either the NP-N or
ANI groups. At the last visit, both the ANI and MND groups had greater neurocognitive decline
from baseline (as indicated by average summary change score) than the NP-N group (-0.11, -
0.13, 0.03 respectively, p=.0002). There was no difference in average summary change
between ANI and MND groups. At the level of individuals, ANI and MND participants were more
likely to experience statistically meaningful decline than NP-N (23%, 30% vs. 13%; p=.004), and
ANI participants were less likely to improve than the NP-N group (7% vs. 21%, p=.008).
Conclusions: It has been suggested that the ANI diagnosis is not valid, does not predict clinical
outcomes, and may be a statistical artifact. Findings from this large longitudinal study
demonstrate that ANI and MND are significant and comparable risk factors for incident cognitive
worsening over 18 to 42 months, indicating that ANI and MND are both clinically important. The
additional specific risk factors for such cognitive decline require further elucidation. |