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Background There are contradicting reports on the associations between Apolipoprotein E4 (ApoE e4) 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 e4 carriers (n = 19) were similar to noncarriers (n = 57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE e4 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 e4 carriers compared with e4 noncarriers. Conclusions In this sample of older HIV-infected individuals, having at least 1 ApoE e4 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.

Psychiatric comorbidities are common in people living with HIV (PLWH) and adversely affect life satisfaction, treatment adherence and disease progression. There are few data to inform the burden of psychiatric symptoms in older PLWH, a rapidly growing demographic in the U.S. We performed a cross-sectional analysis to understand the degree to which symptom burden was associated with cognitive disorders in PLWH over age 60. Participants completed a standardized neuropsychological battery and were assigned cognitive diagnoses using Frascati criteria. We captured psychiatric symptom burden using the Geriatric Depression Scale (GDS) and proxy-informed Neuropsychiatric Inventory-Questionnaire (NPI-Q). Those diagnosed with HIV-associated Neurocognitive Disorders (HAND, n = 39) were similar to those without HAND (n = 35) by age (median = 67 years for each group, p = 0.696), education (mean = 16 years vs. 17 years, p = 0.096), CD4+ T-lymphocyte counts (mean = 520 vs. 579, p = 0.240), duration of HIV (median = 21 years for each group, p = 0.911) and sex (92% male in HAND vs. 97% in non-HAND, p = 0.617). Our findings showed similarities in HAND and non-HAND groups on both NPI-Q (items and clusters) and GDS scores. However, there was a greater overall symptom burden in HIV compared to healthy elder controls (n = 236, p < 0.05), with more frequent agitation, depression, anxiety, apathy, irritability and nighttime behavior disturbances (p < 0.05). Our findings demonstrate no differences in psychiatric comorbidity by HAND status in older HIV participants; but confirm a substantial neurobehavioral burden in this older HIV-infected population.

People with HIV are living longer as combination antiretroviral therapy (cART) becomes more widely available. However, even when plasma viral load is reduced to untraceable levels, chronic HIV infection is associated with neurological deficits and brain atrophy beyond that of normal aging. HIV is often marked by cortical and subcortical atrophy, but the integrity of the brain's white matter (WM) pathways also progressively declines. Few studies focus on older cohorts where normal aging may be compounded with HIV infection to influence deficit patterns. In this relatively large diffusion tensor imaging (DTI) study, we investigated abnormalities in WM fiber integrity in 56 HIV+ adults with access to cART (mean age: 63.9 ± 3.7 years), compared to 31 matched healthy controls (65.4 ± 2.2 years). Statistical 3D maps revealed the independent effects of HIV diagnosis and age on fractional anisotropy (FA) and diffusivity, but we did not find any evidence for an age by diagnosis interaction in our current sample. Compared to healthy controls, HIV patients showed pervasive FA decreases and diffusivity increases throughout WM. We also assessed neuropsychological (NP) summary z-score associations. In both patients and controls, fiber integrity measures were associated with NP summary scores. The greatest differences were detected in the corpus callosum and in the projection fibers of the corona radiata. These deficits are consistent with published NP deficits and cortical atrophy patterns in elderly people with HIV.

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.

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.

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. © Mary Ann Liebert, Inc.

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