Among a group of HIV-infected persons who were virologically suppressed with HAART, neurocognitive impairment was highly prevalent (64%) when determined by a condensed battery of formal neuropsychological performance testing. Neurocognitive impairment was more prevalent within HIV-infected persons of African American race, and persons with lower educational attainment, higher cholesterol levels, and currently using tobacco. Both the MoCA and the AD-8, brief screening tests originally developed for AD, correlated with formal testing, but neither was particularly sensitive as a screening tool (63% for the MoCA and 61% for the AD-8). The combination of tests fared no better.
The relatively high proportion of persons identified with neurocognitive impairment in this study at a single site was similar to previous reports (Tozzi et al. 2007
; Robertson et al. 2007
). Others have identified a lower prevalence (Heaton et al., 2011
; Cysique et al., 2004
) reflecting either differences in the cohorts studied or neuropsychological battery used. For instance, the former study was comprised of individuals with significantly greater educational attainment than the present cohort and the latter study excluded all persons with HIV-associated dementia thus reducing the overall prevalence of neurocognitive impairment. More importantly, the shift from HIV-associated dementia to the milder forms of neurocognitive impairment highlights the need for effective screening tests to identify these more subtle forms (Valcour et al. 2011a
). Early identification is of critical importance with the recent recognition that even these less severe forms of neurocognitive impairment are associated with subsequent progressive cognitive decline and other health implications (Heaton et al. 2012
; Watkins et al. 2012
; Wendelken and Valcour 2012
). Cost effective screening tools which require minimal performance time are clearly needed.
A challenge that has prevented the development of effective screening tools for HAND, is that multiple etiologies (including aberrant immune response (Cysique et al. 2011
), medication neurotoxicity (Marra et al. 2009
), comorbidities (diabetes and hypertension) (McCutchan et al. 2012
), or genetic factors (Apolipoprotein E4 allele) (Chang et al. 2011
)) may contribute. While this study was not specifically designed to evaluate other possible etiologies of neurocognitive impairment, the homogeneity of the sample population with regards to virologic suppression provided the opportunity to look at other factors. We observed that African American racial background, education level, total and LDL cholesterol, and current smoking use were associated with neurocognitive impairment. The relationship to race and education may reflect socioeconomic factors that are well known to impact cognitive functioning and likely serve as a marker of cognitive reserve. The cognitive reserve hypothesis suggests that individuals with greater cognitive reserve, i.e. higher education, exhibit higher resistance to neuropathologic damage (Roe et al. 2010
; Roe et al. 2007
). The associations with cholesterol and smoking are intriguing and suggest that atherosclerosis may contribute to neurocognitive impairment. An association between metabolic factors, most notably obesity, and cognitive impairment was recently reported in another large HIV-infected cohort (McCutchan et al. 2012
). The pro-inflammatory milieu, attributable to HIV and obesity, likely engenders atherosclerotic changes and leads to an underlying vascular component that contributes to neurocognitive impairment (McMurtray et al. 2008
). Cigarette smoking is much more prevalent among HIV-infected persons than the general population (Durazzo et al. 2007
). The negative association of tobacco on cognition provides additional ammunition for care providers to counsel patients to stop smoking (Vellozzi et al. 2009
; Chen et al. 2012
). Further research is needed to understand how these different factors impact cognition in this at risk population.
The search for an effective screening tool for neurocognitive impairment remains a challenge. Our data illustrate that simple screening tools developed for AD may not provide the best discriminator in an HIV-infected population. We observed reduced sensitivity and specificity for the AD-8 compared to previous AD literature (Galvin et al. 2005
). Given that different factors likely contribute to neurocognitive impairment in the current HIV-infected population, it is not surprising that the AD-8, a battery that assesses for functional impairment, performed poorly. The nature of the questions within the AD-8, specifically orientation and memory, make it less applicable to a subcortical process like HIV infection. The AD-8 has been validated in the AD community for either the person or their surrogate informant to complete, and thus, this tool lends itself to a third party assessment of the person’s functional change. In contrast, HIV-infected persons often attend clinic appointments alone (Valcour et al. 2011a
) and often have limited social support networks (Shippy and Karpiak 2005
The MoCA performed better than the AD-8 as manifested within the ROC curves, yielding a fair prognostic score (0.60–0.69) compared to the poor prognostic score of the AD-8 (0.50–0.59) (Yourman et al. 2012
). The MoCA tests 8 cognitive domains and is less likely to be affected by education, comorbidities, or reporting bias (Nasreddine et al. 2005
). However, this screening tool alone failed to adequately distinguish HIV-infected persons with neurocognitive impairment from those with normal cognition. Unlike previous studies that have used the MoCA in an HIV-infected cohort (Koski et al. 2011; Chan et al. 2012
), ours is the first to compare this brief screening test to more formal neuropsychological testing. Notably, the sensitivity of the MoCA was improved to 90% by changing the threshold but the prognostic score remained in the fair
range. While improved sensitivity may be preferable to the clinician, it will increase the number of persons referred for formal neurocognitive testing. Alternatively, the MoCA could be used to identify persons that should be repeatedly monitored. This tactic has been used with other screening tools with average sensitivity such as cervical cancer screening (Wheeler 2007
There are several limitations to the current study. This study was cross-sectional, included persons from a single clinical site, and enrolled only persons whose HIV virus was suppressed with HAART. First, the use of a single site provided certainty that the testing was performed in a similar manner for all persons. Second, the inclusion of only HIV-infected persons who were virologically well controlled was specifically performed in an attempt to limit any confounding that could occur with uncontrolled HIV infection or undetected opportunistic infections. In addition, we did not include HIV uninfected persons within this study. Future studies are needed that include a wide range of HIV-infected persons as well as healthy controls. While the large proportion of African Americans may limit the generalizability, the inclusion of this minority population is highly relevant to the ongoing US HIV epidemic. We did not formally assess activities of daily living and could not make a formal diagnosis of HAND. Using recently developed criteria asymptomatic neurocognitive impairment is characterized by mild neuropsychological impairment in at least two cognitive domains but no functional decline, whereas mild neurocognitive disorder is defined by impairment of at least two domains and reported mild functional decline (Chen et al. 2012
). HIV-associated dementia is defined as having deficits in at least two domains and significant impairment in activities of daily living. While we cannot classify individuals into different HAND categories (asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia), our results do not detract from the primary analysis to evaluate these batteries as screening tools for neurocognitive impairment.
In summary, our study confirms that a large proportion of HIV-infected persons have neurocognitive impairment as assessed by formal neuropsychological testing. The MoCA and AD-8 correlated with formal neurocognitive testing, but the sensitivity of each of these tests was lower than desired for a single screening test. The sensitivity of the MoCA can be improved by using a different threshold value although the number of false positives also increases. Furthermore, like other cognitive screening tests, performance on the MoCA does not define the etiology of neurocognitive impairment. HIV-infected persons with performances < 26 on the MoCA may still require a referral for more comprehensive neuropsychological assessments.