Fat accumulation linked to cognitive impairment in patients with HIV

Central fat accumulation is associated with an increased risk of neurocognitive impairment for HIV-positive patients, according to a study published in the February edition of Neurology. Overall 40% of patients in the study were diagnosed with impairment and increased waist circumference was a significant risk factor. Diabetes was also a factor, but only for patients aged 55 and over.

“Waist circumference, a measure of central obesity and a risk factor for insulin resistance and atherosclerosis contributed to neurocognitive impairment,” comment the authors. They note that their findings accord with research conducted in the general population which “identified…effects on cognition by central obesity as measured by waist circumference or hip-to-waist ratio.”

Antiretroviral therapy can significantly prolong the life expectancy of patients with HIV. However, this treatment can cause a number of side-effects, including metabolic abnormalities. Disturbances in the way the body stores and processes fat are now well-recognised complications of some antiretroviral regimens. There is concern that long-term use of anti-HIV drugs could increase the risk of diabetes and cardiovascular disease.

Rates of neurocognitive impairment among HIV-positive patients are also high. The exact prevalence is controversial. So too are the causes, but these could include metabolic disturbances and diabetes, recognised risk-factors for neurocognitive impairment in the general population.

Investigators from the US CHARTER (CNS HIV Anti-Retroviral Therapy Research) group wanted to clarify the relationship between metabolic disturbances and neurocognitive impairment in patients with HIV.

They therefore designed a cross-sectional study involving 130 patients who received care between 2006 and 2007. These patients completed a standard test to assess their cognitive function. The results were adjusted to take account of age, education, gender and race. Fasting blood samples were obtained to determine levels of total cholesterol, HDL-cholesteral, LDL-cholesterol, triglycerides and the prevalence of insulin resistance. Waist circumference was measured and body mass index (BMI) assessed.

Information on HIV-related factors including duration of infection, use of HIV therapy, CD4 cell count and viral load was also obtained.

The patients had a mean age of 46 years, 57% were white and 87% were men.

Overall, 40% of patients had some form of cognitive impairment.

The first analysis revealed a number of risk factors for this condition. These included older age (48 vs. 44 years, p = 0.02), longer duration of infection with HIV (15 vs. 12 years, p = 0.03) and increased waist circumference (99 vs. 88 cm, p = 0.0005). Patients with impairment were also significantly more likely to have been diagnosed with diabetes (15% vs. 3%, p = 0.007).

A total of ten patients were diabetic and eight (80%) had neurocognitive impairment. This compared to a prevalence rate of 37% among non-diabetic patients.

The investigators explored the apparent association between diabetes and impairment in a larger population totalling over 1300 individuals. They found some evidence of a relationship between diabetes and neurocognitive impairment, but only among patients aged 55 and above.

“Thus, if diabetes contributes to neurocognitive impairment, it may do so only in older patients,” write the authors.

Multivariate analysis was then undertaken to see which metabolic and HIV-related factors increased the risk of impairment.

The first analysis included the 90 patients with a restricted dataset. BMI rather than waist circumference was used as a marker of body composition. The results showed that age (p = 0.027) and BMI (p = 0.039) were both predictors of impairment.

A second model included the 55 patients for whom information on waist circumference was available. BMI (p = 0.038) and waist circumference (p = 0.001) both predicted impairment, as did an AIDS diagnosis (p = 0.027).

The investigators believe that BMI was only significant because “it is a marker of waist circumference.”

They add, “central, rather than generalised obesity conveys increased risk…for neurocognitive impairment.” The authors believe this finding has implications for the use of HIV therapy. “These findings suggest that the selection of combination antiretroviral therapy that induces less central obesity might reduce the risk of HIV-associated brain damage and cognitive impairment.”

A possible mechanism whereby central fat accumulation is contributing to neurocognitive impairment was suggested by the investigators. “Systemic inflammation…or adipose derived hormones may mediate generalised or focal cerebral degeneration that leads to cognitive dysfunction.”

McCutchan JA et al. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology 78: 485-92, 2012