Mental impairment relatively more common in younger people with HIV: brain changes seen but significance unclear

Several presentations at the 15th British HIV Association (BHIVA) conference in Liverpool found further evidence that even people on stable HIV therapy and with good CD4 counts show signs of subtle psychological and neurological impairment, and one study found signs of nerve cell loss in the brain. However, in most of the studies the differences in performance were subtle, and in the study that found brain changes, they were not related to test results.

These studies follow on from the results of a couple of large studies announced at the Conference on Reroviruses and Opportunistic Infections (CROI) in Montreal in February, 2009 (see Heaton, Letendre), which found some evidence of brain impairment in a third to a half of HIV clinic patients and at least moderate impairment (sufficient to noticeably impair complex tasks like driving) in about a quarter to a third.

However these large studies include people who may have many other reasons for impairment in cognition (thinking) such as depression, drink and drug use, previous low CD4 counts and co-infections like hepatitis C. The studies presented at BHIVA therefore looked at smaller groups of patients without any of these confounding factors.

A study from St Mary’s Hospital in west London (Garvey 1) found that, relative to HIV-negative people of their own age, young people with HIV performed relatively worse when given a battery of computer-aided tests designed to measure their muscular co-ordination, memory and learning ability, visual attention and ability to make decisions.

The researchers tested 45 HIV-positive people, most of them men, who were all on HIV treatment. Their average age was 48 (range24-67), they had had an undetectable viral load for at least six months, no current drink or drugs abuse, and did not have hepatitis C.

The St Mary's group found what they called asymptomatic neurocognitive impairment (ANCI) in 14 patients (31%). This was defined as being in the bottom 16% of the general population in test results, when performance was compared to people of similar age in the general population.

Younger age was significantly associated with ANCI; it was present in 54% of the youngest quarter of patients (aged between 24 and 39), 27% of patients in the next quarter (aged 40 to 49), 36% of patients in the next quarter (aged 50 to 57), but only in 10% of the oldest quarter of patients (aged 57 to 67).

This is only a small study, with about 11 people in each age group, so one should not read too much into the results, but the researchers suggest younger people might be more vulnerable to the neurological effects of HIV or could differ from the older people in ways not captured by the study such as socio-economic status.

The other study, from St Thomas’s Hospital, also in south London (Towgood), selected an even more specific group of patients to try and rule out any influences other than HIV infection.

They selected 40 gay men who had been on stable HIV therapy for over six months, had never had a CD4 count under 200, had never abused alcohol or drugs and had not drunk over 25 units of alcohol in any week or smoked cannabis more than once a month in the last four years, had no hepatitis B or C, and no current or past psychiatric conditions. They identified 20 men aged 20 to 40 and 20 men aged 50 to 75 for the study. They put them through a large battery of neuropsychological tests and four different methods of brain imaging. They also put two control groups of 20 HIV-negative gay men with similar characteristics and ages through the same tests and then compared the results.

In this study ‘cognitive impairment’ was defined as results worse than 96% of those expected in the general population.

There was a tendency for the HIV-positive men in both age groups to have more cognitive impairment but this did not reach statistical significance. Fifteen per cent of HIV-positive men had brain impairment compared with 10% of the older HIV-negative men and 9% of the younger ones. Note that even in the HIV-negative men, there was three times as much brain impairment as expected in men of their age. These results were not corrected for age; in other words, the younger men did no better than the older ones, or relatively worse given their age.

The brain images revealed a specific and significant loss of grey matter (the nerve cells that actually do the thinking) from, and only from, a part of the brain called the medial and superior frontal gyrus.

This area, located right above the centre of the forehead, deals with decision-making and choice.

However, there was no correlation between the patients who had cognitive impairment and the ones with loss of nerve cells. The researchers are processing other imaging studies that will look at the connections between nerve cells and the health of other brain cells. For now, they speculate that their imaging techniques might be picking up indicators of future cognitive impairment rather than any current impairment.

Interestingly, decision-making and switching between alternate tasks was the one area of cognitive performance that also seemed to be specifically affected by hepatitis C. In a second study from St Mary’s (Garvey 2), HIV-positive patients infected with hepatitis C in the last six months were compared with patients without hepatitis C.

Forty per cent of patients with acute hepatitis C versus 31% of patients without it met the criteria for brain impairment, even though the hepatitis C-negative patients were on average ten years older. This result was not statistically significant. However the hepatitis C patients did perform significantly more poorly in a particular test that required them to divide their attention between two tasks.

These studies provide additional evidence that a kind of subtle impairment in thinking is more common in people with HIV and also people with hepatitis C. It affects different abilities and parts of the brain than classical dementia, which more often attacks the emotion and memory centres first. Exactly what the clinical significance and future course of this impairment is unclear; much of this impairment is only detectable in tests, would not be readily noticed by patients or their acquaintances, and is often reversible. Some, however, significantly affects ability and seems to be progressive.

The issue of brain impairment, covering the findings from both BHIVA and CROI, will be the subject of an article in the May issue of HIV Treatment Update.