One of the common complications of human immunodeficiency virus (HIV)-1 infection is neurocognitive impairment. This alteration of brain-behavior functioning may range from a subjective sense that one has slowing of thinking and difficulty with memory retrieval to a severe dementia with confusion, mutism, and gross neurologic signs. Numerous studies indicate the percentage of HIV-1—infected patients having any cognitive impairment during the course of their illness to be 38.8% to 54.4% overall¹,²,³ and meeting the full criteria for dementia to be 10.4% to 25.2%,¹,²,³ despite more and more effective antiretroviral therapy.³ With this percentage of people with potential cognitive loss, it follows that clinicians working with HIV-1—infected patients must be sensitive to any signs that cognition is declining, be prepared to refer for a formal neurocognitive evaluation to fully delineate the problems, and, if results show that there are deficits, have a regimen ready for their relief.⁴,⁵

Since 1987, neurocognitive dysfunction in the form of HIV-associated dementia complex has been one of the case-defining criteria conditions for the diagnosis of fully developed acquired immunodeficiency syndrome (AIDS).⁶ Indeed, the presence of severe neurocognitive impairment has been associated with a shortened life expectancy,⁷,⁸,⁹ although now lengthened since the introduction of highly active antiretroviral therapy (HAART).¹⁰ At the beginning of the epidemic, when opportunistic infections were less controllable, the causes of cognitive impairment and dementia were multifactorial, in that those infections and central nervous system (CNS) neoplasia could result in cognitive decline.¹¹,¹²,¹³ This was in addition to the diffuse effects of HIV infection in the brain. Opportunistic infections and tumors could also be reflected as focal neuropsychological deficits, such as strokes. There may also be complications from substance-induced psychiatric disorders (by illicit or prescribed drugs, or chemotherapy.¹⁴,¹⁵,¹⁶ All of the cognitive, behavioral, and emotional conditions just discussed may be characterized, differentiated, and followed by quantitative behavioral methods such as psychological and neuropsychological assessments.

Later in the epidemic, in 1991, as more research confirmed that HIV infection alone could result in significant dementia or subdementia syndromes, a committee of the American Academy of Neurology (AAN) convened to standardize the nomenclature of HIV-associated neurocognitive impairment.¹⁷ This nomenclature remains in force to date and is irrespective of viral load, CD4 count, or physical symptoms. These diagnostic categories depend on cognitive performance and its impact on daily functioning.

Table 5.1 lists the diagnostic criteria for the HIV-1—associated minor cognitive motor disorder (MCMD) that manifest early in the course of the HIV-1 infection. Complaints such as forgetfulness, inattention, difficulty concentrating, mental slowing, and loss of interest or pleasure in everyday activities have often been misinterpreted as a psychological reaction to having contracted this serious illness. Indeed, a number of studies indicate that often the self-report of subjective cognitive disturbance is correlated more with mood disorder rather than with cognitive dysfunction.¹⁸,¹⁹,²⁰ However, many patients do recognize and report their own mental, physical, and mood changes early in the course of the illness, and, whether a sign of cognitive or mood dysfunction, all reports should be taken seriously and thoroughly investigated. This is because it is also known that HIV-1—related cognitive impairment, whether subjectively reported or not, can occur at any time during the course of the systemic infection.²¹ Several investigators have reported that asymptomatic HIV-1—positive patients have measurable cognitive dysfunction compared with HIV-1—negative controls.²²,²³,²⁴ These findings are unrelated to the level of immunosuppression or to depression. Persons with certain risk factors, which lower their “cognitive reserve,”²⁵,²⁶,²⁷ are even more prone to early cognitive decline. Moreover, now into the third decade of the epidemic, there are individuals who are surviving into their 50s and 60s with the infection and elderly who are acquiring the infection at a later age.²⁸ Thus, one now has to consider the possibility of the interaction of the CNS effects of the virus with age-related cognitive changes,²⁹ or, because of its high overall base rate, an incipient dementia of the Alzheimer’s type.

Table 5.2 lists the diagnostic criteria for HIV-1—associated dementia complex. Moderate to severe cognitive deficits, confusion, psychomotor slowing, and seizures may develop as the course of the dementia advances. Patients may appear mute and catatonic. Socially inappropriate behavior, psychosis, mania, and marked motor abnormalities, including ataxia, spasticity, hyperreflexia, hypertonia, and incontinence of bladder and bowel can occur.

Similar to the operationalized diagnostic categorization for Dementia of the Alzheimer Type,³⁰ this classification system requires demonstration of impairment in one or more cognitive domains. The criteria for impairment have been established as a consensus of performance levels on standardized neuropsychometric tests. These tests most reliably and reproduceably express performance in quantitative terms and can do so with considerable precision. The metric often used is a statistical value in terms of units and fractions of the standard deviation from the test’s normative mean.³¹ The patient’s performance at two standard deviations below the published normative mean is usually taken to indicate severe impairment on that test, and thus in the cognitive domain for which that test taps representative abilities. This level corresponds to a ranking at or below the first percentile. Lesser impairment, but at a level considered lower than the low end of the normal range, is operationalized as one and one-half standard deviations (fifth percentile) below the test’s normative mean, and this level has been used to indicate sub—dementia syndromal states such as HIV-related MCMD.

The complete assessment of any patient with neurocognitive impairment should include several areas: the patient’s background and details of current illness; a neuropsychological assessment of the various cognitive domains, an assessment of the impairments’ impact on daily functioning, and measures of any psychological distress. The most basic of assessments are the history and mental status examination.