Traditional risk factors predict neurocognitive impairment in people with HIV

Neurocognitive impairment in people with HIV – loss of memory, poor concentration and declining mental ability – is most likely to be happening for the same reasons as in the wider population, and the risk of impairment does not appear to be associated with HIV infection, a French cohort study has found.

Older age, anxiety and depression, cardiovascular disease and a history of brain injury were strongly associated with neurocognitive impairment, which was detected in 59% of a cohort of French people with HIV.

“Most of the cases were related to non-HIV-related determinants,” comment the authors. “The high prevalence of NCI [neurocognitive impairment] observed in our cohort was neither associated with incomplete viral suppression nor current nor nadir CD4 count. Furthermore, we did not find any association with the current cART [combination antiretroviral therapy] regimen.”

There is considerable interest in the frequency and causes of neurocognitive impairment in people with HIV.

Some studies have suggested that the majority of people, even in the era of modern antiretroviral treatment, have some form of impairment.

However, much of the existing research is limited because it was conducted in highly selected groups of participants who often had pre-existing cognitive complaints.

Researchers in southern France therefore designed a study involving a broad spectrum of people receiving routine HIV care.

To be eligible for the study, participants were required to be aged over 18 and medically stable. Recruitment took place between 2007 and 2009 and a total of 400 people joined the study.

Their neurocognitive function was assessed using standardised tests, which were administered by trained psychologists. Information was also gathered from medical records regarding known risk factors for neurocognitive impairment, such as older age, level of educational attainment, cardiovascular disease, mental health problems such as depression and a history of head injury.

Approximately half the participants also had an MRI scan to see if there was an association between neurocognitive function and atrophy of grey matter in the brain.

The participants had a median age of 47 years and 79% were men. Most (89%) were taking antiretroviral therapy, and 93% of these people had a viral load below 500 copies/ml. Current median CD4 cell count was 515 cells/mm³ and the median nadir CD4 cell count was 260 cells/mm³. Approximately a fifth (19%) of participants had high cholesterol, 4% had a history of cardiovascular disease and 29% were co-infected with hepatitis B or hepatitis C virus.

Neurocognitive testing found a high prevalence of impairment (59%). This was asymptomatic in 20% of participants and mild in 31%; 7% had HIV-associated dementia.

People with impairment were significantly older (p = 0.02), and were more likely to have other health complaints, including a history of cardiovascular disease (p = 0.01), elevated cholesterol (p = 0.04), a history of stroke, brain trauma or neurological disease (p < 0.001), depression (p < 0.001), anxiety (p < 0.001), diagnosis with an AIDS-related neurocognitive condition (p < 0.001), or lower levels of education (p < 0.001).

After controlling for confounding factors, the investigators found that a number of traditional risk factors were associated with an increased risk of impairment.

These included lower levels of education, a history of cardiovascular disease, high cholesterol, anxiety, depression, a history of neurological disease or trauma, and diagnosis with an AIDS-defining neurological disease. No HIV-related factor such as CD4 cell count, viral load, duration of infection with the virus, or use of antiretroviral therapy had a significant association with the risk of impairment.

When the investigators restricted their analysis to the 192 participants without anxiety, depression, a history of brain damage and who also had a higher level of education, they found that only 19% had symptomatic impairment. Restricting analysis further to people without a history of cardiovascular disease reduced the prevalence to just 10%.

The authors believe their results have clinical significance and show the importance of screening for cardiovascular disease, anxiety and depression and when detected, offering appropriate treatment.

The results of the MRI scans showed that people with impairment had significantly lower grey matter volume (p = 0.006). This remained the case after exclusion of participants with the neurological manifestations of AIDS and a history of head trauma (p = 0.03).

“Our study shows for the first time in a large sample a strong association between a reduced volume of grey matter and any stage of NCI,” comment the investigators. “Such results are important for better understanding HIV-associated neurocognitive disorders since they suggest that the cognitive defects in HIV-infected patients are not only due to the functional changes in neural circuitry but could also be the consequence of macrostructural brain lesions.”

They conclude: “All together, our findings suggest that, in patients that are well controlled for HIV infection, cardiovascular and psychiatric disease, in addition to any brain damage including neuroAIDS, and low level of education are related to NCI…screening for cognitive impairment should be accompanied by screening for cardiovascular and psychiatric co-morbidities, in particular depression and anxiety disorders.”