HIV-Associated Neurocognitive Disorders

HIV-associated neurocognitive disorders (HAND) covers a wide range of manifestations from clinically asymptomatic to profound dementia (Table 3.2). Diagnosis of HAND rests on meticulous behavioral neurological examination, detailed neuropsychologic assessment, and evaluation of the patient’s functional status and capabilities [20]. HAND is common in the AIDS population and, with further use of cART along with increased survival of AIDS patients, may become more prevalent [21]. In those patients under treatment with cART, the possibility of developing HAND increases with age along with the presence of cardiovascular risk factors [22].

HIV-associated dementia (HAD) constitutes the most severe form of HAND. With the global use of cART, HAD is relatively less common. Present terminology is based on neuropsychological assessment as well as the mental status examination. It categorizes the neurocognitive status of the AIDS patients into three groups: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HAD [20].

Patients with MND present with mild to moderate neurocognitive decline (>1 SD below the mean of demographically adjusted normative scores) in at least two

Table 3.2 Classification of HIV-associated neurocognitive disorders

HIV-associated neurocognitive dysfunction (HAND) typea

Prevalence in cART-treated HIV+ individuals

Diagnostic criteria [5]

Asymptomatic neurocognitive impairment (ANI)


Impairment in >2 neurocognitive domains (>1 SD)

Does not interfere with daily functioning

Mild neurocognitive disorder (MND)


Impairment in >2 neurocognitive domains (>1 SD)

Mild to moderate interference in daily functioning

HIV-associated dementia (HAD)


Marked (>2 SD) impairment in >2 neurocognitive domains Marked interference in daily functioning

Copyright permission obtained Saylor et al. [22]

SD standard deviation

aWith no evidence of other cause (Adapted from Antinori et al. [20]) cognitive areas. Such impairment generally mildly interferes with the patient’s daily function. Patients with HAD experience moderate to severe cognitive decline (> 2 SDs below demographically adjusted normative means) with severe cognitive impairment in at least two cognitive areas. There is significant loss and difficulty with activities of daily living. Behaviorally, patients with HAD experience impairment of abstract thinking process, verbal fluency, decision-making, and working memory [8]. Interestingly, other memory domains operated by the posterior neocortical and temporo-limbic systems remain relatively intact [8]. Many of these patients do not develop aphasia or apraxia.

In patients with HAD, HIV especially targets and impairs the fronto-striato- thalamocortical subcortical circuits. In addition, HIV also involves and damages other white matter pathways and neural networks, including but not limited to, the temporal and parietal lobes [23]. Utilizing high-resolution brain MRI scans, Thompson et al. [22] assessed the thickness of the cerebral cortex as well as gray- matter thickness in AIDS patients. They generated three-dimensional maps demonstrating that primary motor, sensory, and language cortices were 15% thinner in AIDS patients compared to healthy controls. The investigators noted that thinner frontopolar and parietal tissue loss revealed correlation with cognitive and motor abnormalities. Based on their view of the findings, HIV specifically injures the cerebral cortex [23].

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