Episodic memory deficit in HIV infection: common phenotype with Parkinson's disease, different neural substrates.

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms.

A prospective study revealing a compounded burden of COVID-19, sex, and clinical diagnosis of alcohol use disorder and HIV infection on quality of life, anxiety, and alcohol use.

The COVID-19 pandemic led to unprecedented restrictions to mitigate disease spread, leading to consequences affecting mental health. Many studies examining COVID-19 pandemic effects on well-being and mental health initiated inquiry after the pandemic onset, whereas we used self-report questionnaires obtained before the pandemic to re-assess the same functions during the pandemic. Participants were drawn from our ongoing longitudinal studies of people with HIV infection, alcohol use disorder (AUD), HIV + AUD comorbidity, and controls. We used phone or mail contact to invite all to participate in our COVID phone survey, which included three self-report questionnaires: Health-related Quality of Life (QoL), State-Trait Anxiety Inventory (STAI), and Alcohol Use Disorder Identification Test (AUDIT). Of 218 eligible participants, 86 responded (July 2020-March 2021): clinical (29 men, 23 women; 17 AUD, 21 HIV, 14 HIV + AUD); control (17 men, 17 women). QoL scores declined, and anxiety symptoms increased from pre-COVID surveys in all groups; clinical women reported greater negative changes than the other groups. QoL subscales revealed COVID-related declines in emotional well-being in all groups, with clinical women reporting additional declines in energy, physical and social functioning, health, and pain increase. Clinical men also reported health declines. Although AUDIT scores were stable in all groups between assessments, changes in AUDIT scores were inversely correlated with QoL scores in clinical women; in clinical men, changes in STAI scores were inversely correlated with QoL scores. Although all groups were adversely affected by the pandemic, the negative effects were greater in the clinical group regardless of diagnosis and greatest in clinical women.

Peripheral complement interactions with amyloid ß peptide: Erythrocyte clearance mechanisms.

INTRODUCTION: Although amyloid ß peptide (Aß) is cleared from the brain to cerebrospinal fluid and the peripheral circulation, mechanisms for its removal from blood remain unresolved. Primates have uniquely evolved a highly effective peripheral clearance mechanism for pathogens, immune adherence, in which erythrocyte complement receptor 1 (CR1) plays a major role. METHODS: Multidisciplinary methods were used to demonstrate immune adherence capture of Aß by erythrocytes and its deficiency in Alzheimer's disease (AD). RESULTS: Aß was shown to be subject to immune adherence at every step in the pathway. Aß dose-dependently activated serum complement. Complement-opsonized Aß was captured by erythrocytes via CR1. Erythrocytes, Aß, and hepatic Kupffer cells were colocalized in the human liver. Significant deficits in erythrocyte Aß levels were found in AD and mild cognitive impairment patients. DISCUSSION: CR1 polymorphisms elevate AD risk, and >80% of human CR1 is vested in erythrocytes to subserve immune adherence. The present results suggest that this pathway is pathophysiologically relevant in AD.

Effects of Childhood Trauma and Alcoholism History on Neuropsychological Performance in Adults with HIV Infection: An Initial Study.

Background: Childhood trauma carries heightened risk for neuropsychological impairment and is a frequent concomitant of HIV infection (H) and alcoholism (Alc). Little is known about compounded effects of childhood trauma and these diseases on cognitive and motor functioning. We queried the relation between childhood trauma history (experiencing at least 1 of 13 specified traumas before age 18) and cognitive and motor performance in HIV infection with and without lifetime alcoholism. Methods: Relations between childhood trauma history (Tr) and four performance domains (episodic memory, information processing speed, executive function, and fine motor function) were examined via ANCOVAs covarying for age and education in four HIV groups: 21 H+Alc+Tr, 19 H+Alc, 19 H+Tr, and 25 HComp (H comparison group without Tr or Alc). Results: H+Tr, irrespective of Alc, performed poorly on the episodic memory domain. Specifically, immediate and delayed verbal recall, and immediate visual recall were affected in those with HIV and history of childhood trauma with or without alcoholism history. By contrast, H+Alc+Tr performed faster than H+Alc or H+Tr in information processing speed. Conclusion: The findings of poorer episodic memory in HIV infection with childhood trauma history corroborates previous reports and now extends findings to H+Alc+Tr trimorbidity. The novel interaction of alcoholism and trauma in HIV infection suggests that information processing speed is slowed with trauma history or alcoholism history alone in HIV but not with HIV+Alc+Tr trimorbidity, possibly reflecting greater impulsivity and hyperarousal in multiply-affected individuals.