ApoE ε4 Is Associated With Cognition, Brain Integrity, and Atrophy in HIV Over Age 60.

BACKGROUND: There are contradicting reports on the associations between Apolipoprotein E4 (ApoE ε4) and brain outcomes in HIV with some evidence that relationships may be greatest in older age groups. METHODS: We assessed cognition in 76 clinically stable HIV-infected participants over age 60 and genotyped ApoE. Sixty-one of these subjects underwent structural brain magnetic resonance imaging and diffusion tensor imaging. RESULTS: The median age of the participants was 64 years (range: 60-84) and the median estimated duration of HIV infection was 22 years. Apo ε4 carriers (n = 19) were similar to noncarriers (n = 57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE ε4 carriers demonstrated greater deficits in cognitive performance in the executive domain (P = 0.045) and had reduced fractional anisotropy and increased mean diffusivity throughout large white matter tracts within the brain compared with noncarriers. Tensor-based morphometry analyses revealed ventricular expansion and atrophy in the posterior corpus callosum, thalamus, and brainstem among HIV-infected ApoE ε4 carriers compared with ε4 noncarriers. CONCLUSIONS: In this sample of older HIV-infected individuals, having at least 1 ApoE ε4 allele was associated with decreased cognitive performance in the executive functioning domain, reduced brain white matter integrity, and brain atrophy. Brain atrophy was most prominent in the posterior corpus callosum, thalamus, and brainstem. This pattern of cognitive deficit, atrophy, and damage to white matter integrity was similar to that described in HIV, suggesting an exacerbation of HIV-related pathology; although emergence of other age-associated neurodegenerative disorders cannot be excluded.

Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60.

Individuals infected with HIV are living longer due to effective treatment with combination antiretroviral therapy (cART). Despite these advances, HIV-associated neurocognitive disorders (HAND) remain prevalent. In this study, we analyzed resting state functional connectivity (rs-fc) data from HIV-infected and matched HIV-uninfected adults aged 60 years and older to determine associations between HIV status, neuropsychological performance, and clinical variables. HIV-infected participants with detectable plasma HIV RNA exhibited decreased rs-fc within the salience (SAL) network compared to HIV-infected participants with suppressed plasma HIV RNA. We did not identify differences in rs-fc within HIV-infected individuals by HAND status. Our analysis identifies focal deficits in the SAL network that may be mitigated with suppression of plasma virus. However, these findings suggest that rs-fc may not be sensitive as a marker of HAND among individuals with suppressed plasma viral loads.

The Montreal cognitive assessment to screen for cognitive impairment in HIV patients older than 60 years.

Progress in HIV treatments has led to HIV-infected patients living into their 60s and older. Because HIV-associated neurocognitive disorder (HAND) in older age is associated with more executive dysfunction, cognitive screening instruments tapping this domain may be optimal. We examined the Montreal Cognitive Assessment to identify HAND in 67 HIV-infected patients older than 60 years, of which 40% were diagnosed with HAND. Receiver operating characteristic curve identified an optimal cutpoint of ≤ 25 for HAND with a sensitivity of 72% and specificity of 67%. We conclude that the Montreal Cognitive Assessment has only moderate performance characteristics for cognitive screening of HIV-infected elders.

Deficits in self-awareness impact the diagnosis of asymptomatic neurocognitive impairment in HIV.

A recent national survey of HIV(+) adults noted that nearly three-quarters of cognitively impaired individuals are categorized as having asymptomatic neurocognitive impairment (ANI), lacking documented compromise of everyday function. The clinical impact and long-term consequences of ANI are unknown and the importance of this asymptomatic diagnosis has raised concerns in clinical care settings where competing priorities often exist. In this study, we conducted structured tests of everyday functioning in a sample of HIV(+) subjects over 60 years of age and asked subjects to rate their performance relative to peers. We demonstrate that individuals with neuropsychological testing impairment often lack self-awareness of functional performance deficits. Specifically, ANI subjects rated functional performance similar to that of HIV-negative control subjects, despite noted deficits in objective measures of function. These findings have important implications for use of self-report of function in the diagnosis of HIV-associated neurocognitive disorders (HAND), likely underestimating symptomatic impairment.

Impact of HIV and aging on neuropsychological function.

Cognitive efficiency decreases with age, and advancing age is the leading risk factor for most neurodegenerative disorders that result in dementia. In HIV infection, risk for cognitive impairment is consistently linked to advancing chronological age. As the HIV epidemic enters its fourth decade in the USA, extended life expectancy will likely result in an increased prevalence of cognitive disorders by virtue of these factors. However, it is less clear if HIV potentiates or accelerates the risk for cognitive impairment given that most reports are mixed or demonstrate only a small interaction effect. More critically, it is unclear if HIV will modulate the neuropathology associated with non-HIV cognitive disorders in a manner that will increase risk for diseases such as cerebrovascular and Alzheimer's disease. In the coming years, with increasing numbers of HIV+ patients entering their 60s and 70s, background risk for neurodegenerative disorders will be sufficiently high as to inform this issue on clinical grounds. This review summarizes knowledge of cognition in HIV as it relates to age and presents some emerging controversies.

Screening for cognitive impairment in human immunodeficiency virus.

Recent publications estimate the prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) exceeds 50%, and this rate is likely higher among older patients. Cognitive impairment may impact medication adherence, and symptomatic impairment has been linked to all-cause mortality providing some impetus for early detection. There are currently insufficient data to inform solid recommendations on screening methods. Most HIV-specific tools have poor performance characteristics for all but the most severe form of impairment, which accounts for <5% of cases. Reliance on symptoms is likely to miss a substantial proportion of individuals with HAND due to poor insight, confounding mood disturbances, and lack of well-informed proxies. In the aging HIV-positive population, broader screening tools may be required to allow sensitivity for both HIV and neurodegenerative disorders. We describe the clinical presentation of HAND, review existing data related to screening tools, and provide preliminary and practical recommendations in the absence of more definitive studies.