Módulo 3 – Curso pós-graduado – VIH e Envelhecimento

Neurocognitive Disorders in HIV Infected Patients

Risk factors for neurocognitive disorders in the setting of HIV infection

Autor: Prof. DoutorVictorValcour, MD PhD (Memory and Aging Center, University of California, San Francisco, USA)

Comorbidities and neurocognitive impairment

Heaton et al. have also detailed the frequency of HAND by comorbidity status.1 Hence, for the individuals in their study that had only incidental confounding factors, that means they did not have other comorbidities, the probability of neurocognitive impairment was less than 40%. However, as the number of other risk and confounding factors increase, the rate of impairment was doubled to around 80%. Even though this is probably a higher rate than expected (due to the poor rate of HIV suppression), it is clear the large contribution of other factors not related to HIV, as risk factors for cognitive impairment.

The comorbidities that this study reported as risk factors were:

  • Cerebrovascular disease, particularly important as we approach an aging population
  • Head injury/brain trauma, since many patients may have an history of drug or alcohol abuse and associated head injuries
  • Depression
  • Low educational attainment/low reading level, a premorbid brain reserve issue not related to HIV that increases the patient risk for failing to do well on neurocognitive tests
  • Systemic medical illness

Cerebrovascular disease is very important, even though most of the information in the current literature results from studies that took place at a time when treatment of risk factors (smoking, blood pressure, high cholesterol, diabetes) in this population was not as aggressive as nowadays. Some studies have reported that the performance on cognitive tests worsens with the increase of the number of risk factors.

White matter injury is a radiological marker of cerebral small vessel ischemic disease and was a common feature in HIV patients before HAART treatment. These lesions seem to be higher in HIV patients over 60 and it was observed that the higher the number of lesions the poorer the performance on neurocognitive tests.3 When considering HIV factors related to these lesions, no correlations were found but associations with smoking, diabetes and high blood pressure were observed.4

Over the last decade, there has been an increase in patients diagnosed with stroke who have coexisting HIV infection, and this rate is probably disproportionally increasing in women com- pared to men.5,6This increase may be at least partially explained by the increasing age of the HIV population but also by factors related to HIV infection, including chronic inflammation and activation of the immune system and endothelium, and higher rates of traditional vascular risk factors including smoking and possibly substance abuse. Hence, the management of modifiable risk factors for cerebrovascular disease plays an important role for the protection of cognitive capacity of HIV patients.

Depression is a controversial risk factor because it is very frequent in people with HIV and the inflammation quantified in CSF or plasma seem to correlate to depression, thus suggesting that depression is not exclusively a risk factor as much as it is a consequence of HIV itself. However, if somebody is markedly depressed, the results from cognitive tests would be very difficult to interpret, which may result in some confounding.

With regard to systemic illnesses as risk factors for cognitive impairment, liver dysfunction has received the most interest, maybe because of the high prevalence of hepatitis C co-infection in HIV patients. However, the literature does not confirm an evident correlation between having hepatitis C and performing poor on cognitive tests in people with HIV, in the absence of liver fibrosis or liver failure.7 Liver fibrosis correlates to cognitive performance independent of hepatitis C virus (HCV) and HIV, but the pattern of neuropsychological deficit associated with fibrosis was not typical of Minimal Hepatic Encephalopathy, a cognitive confusion that occurs in people without cirrhosis (only liver fibrosis). We have since looked at markers of inflammation, which correlate better than the fibrosis itself; thus, the correlation to liver fibrosis, itself, may simply be due to a common underlying etiology in inflammation.

A formula created by Amy Justice, called Veterans Aging Cohort Study (VACS) index, quantifies a concept that aims to capture the burden of multi-morbidity in HIV patients. It includes HIV factors like T CD4 cell count, the HIV RNA level, but it also includes anemia, liver fibrosis (FIB-4 index), kidney function and hepatitis C infection.8 The VACS index has proven to predict mortality better than CD4+ and viral load alone, predicts medical intensive care admissions and is congruent with geriatric principles as it focuses on global vulnerability from multiple organ systems rather than one disease. Marquine et al. have also demonstrated that changes in VACS index are linked to incident cognitive impairment.9 This association may be explained by inflammation, since people who have higher levels of inflammation have multiple organ involvement.

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