Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women

Abstract

Objective: Neurocognitive studies of HIV typically target executive functions dependent on frontostriatal circuitry. The integrity of medial temporal systems has received considerably less attention despite high hippocampal viral load. Studies also predominately involve HIVϩ men, though HIVϩ women may be at increased risk for cognitive dysfunction due to the high prevalence of psychosocial/mental health problems and lower educational attainment. Our aim was to conduct a preliminary investigation of episodic memory and its neural correlates in HIV-infected and at-risk uninfected women.Methods: Participants included 54 HIVϩ and 12 HIVϪ women (mean age ϭ 43 years; 86% African American) recruited from the Chicago site of the Women's Interagency HIV Study. Participants completed standardized tests of verbal and visual episodic memory, working memory, and executive function. A subset of 11 women also underwent functional MRI during a delayed verbal episodic memory task.Results: HIV serostatus predicted significantly lower immediate and delayed verbal episodic memory, working memory, and visual memory. Preliminary neuroimaging findings revealed group differences in bilateral hippocampal function, with HIVϩ women showing decreased activation during encoding and increased activation during delayed recognition. These alterations correlated with worse episodic verbal memory. Conclusions:Verbal episodic memory deficits are evident in HIVϩ women and may be associated with hippocampal dysfunction at both encoding and retrieval. Neurology Until recently, the functional integrity of medial temporal systems in neuroAIDS has received little attention despite considerable evidence of hippocampal injury associated with HIV. Brain viral loads of HIV are particularly high in the hippocampus.1,2 Postmortem evidence of neuroinflammation by microglial/macrophage activation was found to be high in the hippocampus of HIVϩ individuals treated with highly active antiretroviral therapy (HAART), higher even than levels found in pre-HAART neuropathologic studies.3 Regional neurodegeneration of hippocampus and putamen each contributed unique variance in prediction of antemortem neurocognitive status in HIV. 4 A functional MRI (fMRI) study of well-educated HIVϩ men demonstrated reduced signal intensity in right posterior hippocampus, right inferior frontal gyrus, and left lingual gyrus during encoding of scenes.5 Further detailed multimodal investiga-

Cognitive function in women with HIV

“…35 A previous WIHS functional MRI study suggests that the deficits in verbal learning and memory observed in this study might reflect hippocampal dysfunction. 11 Compared to HIV-uninfected controls, HIV-infected women showed hippocampal hyperactivation during verbal encoding and hippocampal hypoactivation during recall. 11 Alterations in hippocampal function during verbal encoding and recall were associated with lower HVLT performance.…”

“…11 Compared to HIV-uninfected controls, HIV-infected women showed hippocampal hyperactivation during verbal encoding and hippocampal hypoactivation during recall. 11 Alterations in hippocampal function during verbal encoding and recall were associated with lower HVLT performance. Alterations in prefrontal cortex also likely contribute to the observed deficit in delayed verbal memory, because HIV-associated deficits in verbal memory are characterized by deficits in executive control of encoding and retrieval mechanisms, 25 a pattern consistent with frontal-subcortical involvement.…”

“…Our second aim was to investigate the pattern and magnitude of impairment across cognitive outcomes. Based on prior WIHS findings, 11,14 we predicted that HIV-infected women would show deficits in psychomotor speed, attention, verbal learning, and memory.…”

Problematic Alcohol Use Among Individuals with HIV: Relations with Everyday Memory Functioning and HIV Symptom Severity

“…Among HIVinfected individuals, problematic alcohol use is associated with worse HIV health outcomes [e.g., 2,5,7,8,[11][12][13][14][15][16][17][18][19] which ostensibly result in increased HIV symptom severity and lower overall quality of life. Adding to the clinical profile, HIV disease progression (i.e., heightened symptom burden) is commonly associated with neurocognitive impairment [24][25][26][27][28]. Given the high prevalence of alcohol problems among HIV-infected individuals coupled with its observed negative impact on memory functioning, routine screening for problematic alcohol use in HIV care settings is thus imperative [14,89].…”

“…HIV disease progression poses significant risk for compromised cognitive efficiency (e.g., executive dysfunction) and memory functioning (as indexed by neuropsychological testing) [24][25][26][27][28], and although antiretroviral therapy (ART) can reduce neurocognitive impairment [29], mild forms still persist in a large proportion of individuals with HIV [30,31]. Of note, cognitive impairment, and memory dysfunction more specifically, is associated with worse treatment outcomes among HIV-infected individuals [27,[32][33][34] and is known to reduce the effectiveness of interventions aimed at optimizing adherence and reducing risk behavior [35].…”