A French study has reported that neurocognitive impairment (NCI) was common in a group of unselected HIV positive adults, but that this was not related to either HIV or HIV treatment.
The study highlighted the importance of preventative measures such as control of cardiovascular risks, and the screening of anxiety and depression, in addition to effective ART. This will become increasingly important with an ageing population and increasing life expectancy.
This was a prospective study from Fabrice Bonnet and colleagues from the ANRS Aquitaine Cohort that consecutively enrolled 400 patients from five clinics between 2007-2009, and is notable for the inclusion of an MRI substudy for white and grey matter volumes. Results were published in the 28 January 2013 edition of AIDS.1
The study included standard intensive neuropsychological and cognitive assessment including difficulties in everyday life, plus medical history that included drug, alcohol and substance use.
If NCI was present, the severity was then categorised as asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) or HIV associated dementia (HAD), based on a score defined against a demographically adjusted normative score using U.S. norms in at least two ability domains, without any symptoms.
Baseline characteristics included median age 47 years (42-53), median CD4 cell count 515 cells/mm3 (350-700) and 79% of patients were male. Approximately half acquired HIV as MSM, 37% heterosexual and 15% from IDU. Most (89%) were on ART and 85% had viral load <400 copies/mL. Although 24% were diagnosed as AIDS stage, only 5% had neuro AIDS. Coinfection with HCV or HBV was 22% and 7%, respectively.
The study reported NCI in 58% (95%CI 53.5 - 63.4%) of participants (234/400) with severity categorised as 20% ANI, 31% as MND and 7% with HAD. Neurocognitive tests detected similar rates of NCI in people reporting symptoms (62%) or no symptoms (57%). Motor function difficulties also related to poor cognition.
In multivariate analysis, symptomatic NCI was independently associated with (Odds Ratio; 95%CI): history of neurological AIDS event (OR 4.46; 95%CI 1.59, 14.9); lower level of education (OR 3.39; 95%CI 1.48, 7.80), anxiety (OR 2.93; 95%CI 1.67, 5.14), depressive symptoms (OR 2.11; 95%CI 1.23, 3.63), and any history of brain damage (OR 2.05; 95%CI 1.18, 3.58).
Perhaps surprisingly, symptomatic NCI was still reported in 18% (36/192) patients who had none of these associated factors,
No association was reported between NCI and HIV related factors including CD4 cell count and nadir, viral load, hepatitis coinfection, use of either efavirenz or AZT, or, notably, with CPE score. While generalised anxiety, depressive symptoms, alcohol dependence and neurological disease were all found to be related (a P-value of 0.46 and 0.004 respectively).
In the 178 patients with evaluable MRI scans, NCI of any category was associated with significantly reduced grey matter volume [650.9 (95% CI 639.7-662.1) vs. 627.3 (95%CI 614.8 - 639.9); p=0.006], and this remained significant when 14 people with previous CNS injury were excluded from the analysis (p=0.03). Although a trend appeared to relate to grey matter volume and severity of NCI, this was not statistically significant (p=0.098).
A significant association between cognition and poor lower limb muscle performance: 58% of patients with NCI also had lower limb muscle performance evaluated by 5STS test vs. 46% of those with no NCI (P=0.04). Those with symptomatic NCI (MND and HAD), 63% of them had a poor 5STS test performance compared to 47% of those with without symptomatic NCI (P=0.004). Poor lower limb performance in HIV-infected patients may be as a result of muscle function rather than NCI as patients performed well in balance tests.
This study is notable for being a representative clinic cohort with reasonable size data but reported similar prevalence to that seen in other European and U.S. studies, which tended to be in selected populations.
Nearly everyone in the study was associated with some level of dysfunction (if the positive cognitive test results for people with no cognitive complaints are included) raising the difficulty of interpreting the practical significance in the absence of an HIV negative control group.
Although most dysfunction was either asymptomatic or mild, 8% of people in this well treated cohort had severe cognitive disorder categorised as HIV-associated dementia.
Bonnet F et al. Cognitive disorders in HIV-infected patients: are they HIV-related? AIDS 2013, 27:391-400. (28 February 2013).
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