Feature Article Cognitive Effects of HIV-1 Infection By Frances L. Wilkie, PhD, Karl Goodkin, MD, PhD, FAPA, M. H. van Zuilen, Mary D. Tyll, PhD, Robert Lecusay, and Tony Edwin, MD ABSTRACT The major neurological complication of human immunod- eficiency virus type 1 (HIV-1) infection is cognitive impair- ment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cog- nitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstrac- tion and executive functions observed in later stages of infec- tion. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical signifi- cance of mild cognitive impairment as a significant risk fac- tor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test perfor- mance is also reviewed. CNS Spectrums 2000;5(5):33-51 INTRODUCTION The human immunodeficiency virus type 1 (HIV-1) enters the central nervous system (CNS) as early as 14 days after initial infection. 1 The most common neurological com- plication of HIV-1 infection of the brain is cognitive impairment, which can range in severity from a subclinical cognitive inefficiency to a minor cognitive-motor disorder (MCMD) to HIV-1-associated dementia (HAD), a severe dementing illness formerly referred to as acquired immun- odeficiency syndrome (AIDS) dementia complex. According to the American Academy of Neurology (AAN) 2 and as dis- cussed by Goodkin, 1 HAD reflects a loss in cognitive func- tion accompanied by a moderate to severe decline in functional status (reflected in a diminished ability to work and carry out activities of daily living) with no other demonstrable etiology. In contrast, the cognitive dysfunc- tion in MCMD has a less significant impact on functional status. In evaluating cognitive impairment associated with HIV-1, it is important to rule out other causes of cognitive dysfunction that might be associated with opportunistic infections (eg, CNS toxoplasmosis), neoplasms (eg, CNS lymphoma), 4 and delirium. PREVALENCE AND SEVERITY The prevalence and severity of cognitive impairment in HIV-1 infection increases as the disease progresses. A sub- clinical cognitive impairment without functional status changes may occur in as many as 22% to 30% of asympto- matic HIV-1—seropositive individuals, 56 increasing to 40% to 50%, respectively, of individuals during the early and late symptomatic stages of infection. 7 MCMD prevalence has been studied less, but may occur in as many as 25% to 30% of HIV-1—infected individuals during the early symptomatic stage and in 40% or more of those with AIDS. HAD has declined from a cumulative prevalence ranging from 17% to 25% 8>9 during the course of AIDS to a cumulative preva- lence ranging from 7% to 10%. 10 COGNITIVE FUNCTION HIV-1 infection has been characterized as affecting pri- marily subcortical and frontostriatal brain processes. 11 " 14 The brain areas affected by HIV-1 infection are primarily the white matter and deep gray structures, with the cerebral cortex generally free from infection. Specific subcortical structures affected in HIV-1 infection include the basal ganglia, thalamus, pons, and brain stem. Cognitive deficits may occur in attention, the speed of processing information, memory, abstraction skills (eg, the ability to shift sets, form concepts), and fine motor skills. A brief review of some of the specific cognitive processes affected by HIV-1 infection follows. Language In HIV-1 infection, there may be a decrease in verbal fluency (eg, the ability to quickly name as many words as possible that begin with a specific letter or to name as many animals, fruits, or vegetables during a 60-second interval for each category). In contrast, many other language processes (eg, vocabulary and confrontation naming) may remain rela- tively stable. 12 - 15 Memory The nature of the memory impairment observed in HIV-1 infection resembles that seen in Huntingdon's disease, a sub- cortical brain disease with a pattern of memory impairment different from that of cortical dementias, such as Alzheimer disease. 16 Specifically, individuals with either subcortical or cortical brain disease have difficulty during the acquisition please turn to page 46 ^• Dr. Wilkie is research professor, Dr. Goodkin is professor, Ms. van Zuilen is research, assistant, Dr. Tyll is senior research associate, and Mr. Lecusay is research associate, all in the Department of Psychiatry and Behavioral Sciences at the University of Miami School of Medicine in FL Dr. Goodkin is also professor in the Department of Neurology at the University of Miami School of Medicine in FL. In addition, Dr. Goodkin is professor and Ms. van Zuilen is research assistant in the Department of Psychology at the University of Miami in Coral Gables, FL. Dr. Edwin is research associate in the Department of Psychiatry at the State University of New York in Buffalo, NY. Acknowledgments: This work was supported by National Institutes of Health grants AG52321 (Dr. Wilkie), MH58532, and MH20004 (Dr. Goodkin). Volume 5 - Number 5 • May 2000 33 CNS SPECTRUMS