Asymptomatic neurocognitive impairment in people with HIV does predict later neurocognitive symptoms

People with HIV who showed evidence of asymptomatic neurocognitive impairment at study entry were nearly twice as likely to progress to symptomatic HIV-associated neurocognitive disorders as those with initially normal tests, according to research presented at the Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) in July in Vancouver.

Background

While the prevalence of AIDS-defining dementia has declined dramatically since the advent of effective antiretroviral therapy (ART), less severe HIV-associated neurocognitive disorders remain common among people living with HIV.

HIV-associated neurocognitive disorder, or HAND, includes three levels of severity:

• Asymptomatic neurocognitive impairment: at least mild neuropsychological impairment in two or more domains but no decrease in everyday functioning;

• Mild neurocognitive disorder: at least mild neuropsychological impairment in two or more domains with at least mildly decreased everyday functioning;

• HIV-associated dementia: overall neuropsychological impairment of at least moderate severity and major decline in everyday functioning.

Neurocognitive impairment can be defined as ‘asymptomatic’ because psychological tests of neurocognitive abilities including fine movement, memory, fluency and executive function (prioritisation and organisation) can detect substandard performances in one or more areas that are too subtle to be noticed by the person themselves or people who know them, or dismissed as everyday poor memory or clumsiness.

A large US study, the CHARTER cohort, indicated that approximately half of people living with HIV have some form of HIV-associated neurocognitive disorder, though asymptomatic impairment that could only be detected in the specialised tests was most common, found in 70% of cases. Other studies that use different definitions of HAND have failed to find increased rates in gay men with HIV when compared with matched HIV-negative gay men, and have found rates little higher than in the general population in some other groups too.

There has been controversy over two issues. Firstly, are the deficits detected related to HIV at all, or simply more common in people with lifestyles that are also associated with HIV risk? And secondly, are such test results predictive of progression to more serious and noticeable neurocognitive impairment? The current study aimed to shed light on these questions.

The study

Sean Rourke of the University of Toronto and colleagues looked at the prevalence and progression of HIV-related neurocognitive problems among participants in the Ontario HIV Treatment Network Cohort Study.

Although one recent study of the CHARTER cohort found that improvement in neurocognitive scores was fairly common over time too, decline was somewhat more common, and another recent CHARTER study found that asymptomatic neurocognitive impairment was associated with a two- to six-fold increased risk for developing symptomatic HAND. The present study aimed to replicate and extend these results in a Canadian population.

This analysis included 679 adults receiving HIV care in Toronto who completed at least two annual neuropsychological assessments. More than 80% were men, 62% were white, the mean age was 45 years and the mean education level was 14 years.

Most participants (83%) were taking ART and 72% had an undetectable HIV viral load. While 45% had a current CD4 T-cell count above 500 cells/mm³, 58% had previously had a nadir or lowest-ever count below 200 cells/mm³ (an indication for an AIDS diagnosis, and also associated with neurocognitive impairment). More than a quarter (27%) were diagnosed with depression, 29% were current cigarette smokers, 16% reported non-medical drug use and 17% reported heavy alcohol use. Medical comorbidities were common, including diabetes (7%), cardiovascular disease (15%), hypertension (17%) and chronic lung disease (21%). Many of these are risk factors for neurocognitive disorders.

Neuropsychological testing was performed annually using a brief battery of tests that included measures of cognitive processing speed, attention/working memory and learning/memory. Cognitive symptoms or deficits were assessed using the four-item Medical Outcomes Study HIV Health survey cognitive functioning scale, which assesses difficulties with memory, attention, reasoning, and concentration during the past four weeks.

People with a global deficit score less than 0.5 were considered to have normal neurocognitive function, those with a score of 0.5 to 2 were considered to have asymptomatic neurocognitive impairment or mild neurocognitive disorder depending on whether they also had self-reported cognitive symptoms, and everyone with a score over 2 was classified as having dementia.

At baseline 357 participants had normal neuropsychological tests, while 322 (47%) showed evidence of asymptomatic neurocognitive impairment. Over a median 34 months of follow-up, 143 participants (21%) experienced progression to symptomatic HAND.

Participants who started with asymptomatic neurocognitive impairment were more likely to progress to symptomatic HAND than those with normal neurocognitive function at baseline (27% vs 15%, respectively). Participants with asymptomatic neurocognitive impairment at their first visit also had a significantly shorter time to progression than those with normal tests at baseline.

In a multivariate analysis, participants with asymptomatic neurocognitive impairment at baseline were 1.8 times more likely than those with normal tests to experience earlier progression to symptomatic HAND (hazard ratio [HR] 1.79).

Female sex (HR 1.58), depression (HR 1.87), current smoking (HR 1.73) and cardiovascular disease (HR 1.67) were also significantly associated with increased risk of progression. Conversely, higher education level and speaking English at home were significantly associated with lower risk of progression (HR 0.94 and 0.60, respectively), while undetectable plasma HIV viral load showed a trend toward a protective effect (HR 0.72).

"Asymptomatic neurocognitive impairment diagnosis is associated with increased risk of progression to symptomatic HAND (i.e., mild neurocognitive disorder or HIV-associated dementia)," the researchers concluded.

"Regular monitoring (and retesting) of persons with asymptomatic neurocognitive impairment may help to identify those who may progress with neuropsychological impairments," they suggested. "Treatment of cardiovascular risk factors and depression are important avenues for intervention and may delay the onset or progression of HAND."