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Scholarly Works (11 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2022)

HIV and aging have adverse effects on the central nervous system (CNS), including chronic inflammation, and confer risk for neurocognitive impairment (NCI) and functional decline. Cannabis may exert beneficial effects on the CNS in people with HIV (PWH) due to its anti-inflammatory and immunomodulatory properties. Yet to date, there is scant literature examining the role of cannabis and cannabinoids in this population. This staple dissertation aimed to elucidate the relationships among cannabis exposure, central and peripheral inflammation, and neurocognitive and functional impairment in PWH.

Study 1 (N = 952; Watson et al., 2020). PWH with past-year cannabis use and past cannabis use disorder had lower rates of NCI (OR = 0.53, p = 0.009) and better performance in learning (b = 2.70, p = 0.02) and verbal fluency (b = 2.86, p = 0.02) compared to non-cannabis-using PWH. Cannabis use was unrelated to NCI among people without HIV.Study 2 (N = 234; Watson et al., 2021). Lower levels of pro-inflammatory biomarkers CCL2/MCP-1 and CLCX10/IP-10 in cerebrospinal fluid were observed among daily cannabis-using PWH with Δ9-tetrahydrocannabinol (THC) positive urine toxicology compared to non-cannabis-using PWH (p = 0.02; p = 0.04). Plasma biomarkers showed no differences by cannabis use. Lower levels of CCL2/MCP-1 and CLCX10/IP-10 were associated with better learning (b = –6.3, p = 0.02; b = –2.3, p = 0.04).

Study 3 (N = 297; Watson et al., in preparation). In a longitudinal cohort of older adults with HIV, occasional cannabis use (≤ weekly) was associated with better overall global neurocognition (b = 0.50, p = 0.03), while THC+ urine toxicology showed negative short-term effects on memory (b = –0.27, p = 0.03). Rates of neurocognitive decline and functional declines did not differ by cannabis use.

Collectively, these studies extend pre-clinical cannabinoid findings identifying beneficial cannabis effects on neuroinflammation and neurocognition in the context of HIV and THC-specific short-term detrimental impacts in older adults. Results highlight the complex influence of cannabis on CNS function, which varies by dose/frequency, cannabinoid content, and pro-inflammatory disease context, and can inform future development of cannabinoid-based therapeutics to treat neuroinflammation and improve downstream outcomes in HIV and aging.

    Cover page: Effects of Cannabis Exposure on Neuroinflammation, Neurocognition, and Everyday Function in HIV and Aging
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2021)
    Introduction: Growing access to both legitimate and dubious sources of health information makes accurate source memory increasingly important, yet it may be negatively impacted by conditions that impair prefrontal functioning, including HIV. This study hypothesized that instructions supporting source encoding on a health-related memory task would disproportionately benefit source memory of people with HIV (PWH), and to examine the pattern of source memory errors that are observed.Method: 102 individuals (61 HIV+, 41 HIV-) completed comprehensive neurobehavioral (including health literacy) and neuromedical evaluations, and were randomly assigned to one of two conditions for a health-related memory task: Attend to Source Instructions explicitly participants to attend to the source of health statements presented to them, which were either health professionals or lay-persons, whereas no such instruction was provided in a Control Instructions condition.Results: There was no significant interaction of HIV status by condition or main effect of HIV (ps>.05). There was a main effect of condition whereby those who received Attend to Source Instructions performed better on item-corrected source memory than those in the Control Instructions condition (p =.04). Those who received Control Instructions were more likely to misattribute the source of the health information to a health professional when the correct source was a lay-person (Cohen's d = -0.53), which was correlated with poorer overall cognitive performance (p =.008) and performance-based measures of health literacy (ps<.05).Conclusions: Given that people are rarely reminded to attend to the source of new health information in the real world, the risk for misattributing health information to a qualified health professional in the absence of such instructions raises the concern that people may readily incorporate questionable health recommendations into their health regimen, particularly among persons with poorer cognitive functioning and lower levels of health literacy. This may have significant downstream health consequences such as drug interactions, side effects, and inefficacy.
      Cover page: Misattributions of the source of health-related information in HIV disease
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2020)
      The Met-allele of the COMT Val158Met polymorphism slows metabolism and increases bioavailability of dopamine (DA) in the prefrontal cortex compared to the Val-allele. Healthy Met-carriers outperform Val-carriers on executive function (EF) tests, yet this 'advantage' disappears in methamphetamine (METH) dependence. Met-carriers may be disproportionately vulnerable to METH-related perturbations of DA, yet it is unknown whether COMT modulates METH effects on CSF DA biomarkers. Participants were 75 METH+ and 47 METH- men who underwent neurocognitive testing, COMT genotyping, and lumbar puncture. CSF was assayed for DA and its metabolite, homovanillic acid (HVA). Separate linear models regressed DA, HVA, and HVA/DA ratios on COMT, METH and their interaction. Pearson correlations examined associations between DA and EF. Significant interactions indicated that METH+ had lower DA and higher HVA/DA ratios among Met/Met, but not Val/Met-or Val/Val. Met/Met-exhibited the highest DA levels among METH-, whereas DA levels were comparable between Met/Met-and Val-carriers among METH+. Higher DA correlated with better EF in METH- Met/Met, but did not predict EF in the entire sample. DA was expectedly higher in METH- Met/Met, yet a discordant genotype-phenotype profile emerged in METH+ Met/Met, consistent with the notion that slow DA clearance exacerbates METH-associated DA dysregulation.
        Cover page: COMT val158met genotype alters the effects of methamphetamine dependence on dopamine and dopamine-related executive function: preliminary findings
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2022)

        Background and objectives

        To investigate sociodemographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia.

        Methods

        Within a community-based cohort, diagnoses of MCI were made with a published algorithm. Diagnosis of dementia was based on clinical consensus. Cox regressions estimated hazard ratios of incident MCI associated with several predictors. Modified Poisson regressions estimated relative risks associated with predictors of diagnostic status at follow-up after incidence.

        Results

        Among 2,903 cognitively normal participants at baseline, 752 developed MCI over an average of 6.3 (SD 4.5) years (incidence rate 56 per 1,000 person-years). Presence of APOE ε4 and higher medical burden increased risk of incident MCI, while more years of education, more leisure activities, and higher income decreased this risk. Of the incident MCI cases, after an average of 2.4 years of follow-up, 12.9% progressed to dementia, 9.6% declined in functioning and did not meet the algorithmic criteria for MCI but did not meet the clinical criteria for dementia, 29.6% continued to meet MCI criteria, and 47.9% no longer met MCI criteria. Multidomain MCI, presence of APOE ε4, depressive symptoms, and antidepressant use increased the risk of progression to dementia.

        Discussion

        This community-based study showed that almost half of the individuals with incident MCI diagnoses were classified as cognitively normal at follow-up. Predictors of incident MCI demonstrably differed from those of subsequent MCI course; these findings can refine expectations for cognitive and functional course of those presenting with MCI.
          Cover page: Predictors of Incident Mild Cognitive Impairment and Its Course in a Diverse Community-Based Population
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2020)

          Background

          Aging and HIV have adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of neurocognitive impairment (NCI). Previous research suggests the nonacute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti-inflammatory properties. In the current study, we examined the independent and interactive effects of HIV and cannabis on NCI and the potential moderation of these effects by age.

          Methods

          Participants included 679 people living with HIV (PLHIV) and 273 people living without HIV (HIV-) (18-79 years old) who completed neurocognitive, neuromedical, and substance use assessments. NCI was defined as a demographically corrected global deficit score ≥ 0.5. Logistic regression models examined the effects of age, HIV, cannabis (history of cannabis substance use disorder and cannabis use in past year), and their 2-way and 3-way interactions on NCI.

          Results

          In logistic regression models, only a significant interaction of HIV X cannabis was detected (P = 0.02). Among PLHIV, cannabis was associated with a lower proportion of NCI (odds ratio = 0.53, 95% confidence interval = 0.33-0.85) but not among HIV- individuals (P = 0.40). These effects did not vary by age.

          Conclusions

          Findings suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV. Further investigations are needed to refine the effects of dose, timing, and cannabis compound on this relationship, which could inform guidelines for cannabis use among populations vulnerable to cognitive decline.
            Cover page: Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV.
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2019)
            Objective: Neurocognitive impairment (NCI) is a well-known complication of human immunodeficiency virus (HIV) infection and may be influenced by a number of psychological factors. We examined the relationship between NCI and mental health disorders, including posttraumatic stress disorder (PTSD), in a cohort of 189 active-duty and retired U.S. military men living with HIV. Methods: Participants completed selected modules of the Composite International Diagnostic Interview (CIDI) to ascertain the presence of PTSD, major depressive disorder, and other mental health diagnoses. We also obtained demographic data, including history of head trauma, via personal interview. NCI was assessed with a comprehensive battery of standardized neuropsychological tests. Results: The median age of study subjects was 36 years (interquartile range [IQR] 28 to 43) and median total years of education was 14 (IQR 12 to 16). NCI was diagnosed in 19% of subjects. Individuals with and without a history of PTSD were similar with respect to most HIV-related characteristics; however, the former were significantly more likely to have a prior acquired immunodeficiency syndrome (AIDS) diagnosis. In multivariate analysis, lifetime history of PTSD was independently associated with NCI (odds ration [OR] = 6.12; 95% confidence interval [CI] = 1.85, 20.27), while a history of head of trauma was negatively associated (OR = 0.37 95% CI = 0.15,0.92). Conclusions: Our findings demonstrate that PTSD is an important predictor of NCI in this U.S. military cohort. HIV-infected individuals with cognitive difficulties should be screened for mental health disorders, including PTSD, and prospective studies of the longitudinal relationship between PTSD and NCI, as well as the impact of PTSD treatment on future NCI, are warranted.
              Cover page: Posttraumatic Stress Disorder and Neurocognitive Impairment in a U.S. Military Cohort of Persons Living with HIV.
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2023)
              Cannabis use is rapidly increasing among older adults in the United States, in part to treat symptoms of common health conditions (e.g., chronic pain, sleep problems). Longitudinal studies of cannabis use and cognitive decline in aging populations living with chronic disease are lacking. We examined different levels of cannabis use and cognitive and everyday function over time among 297 older adults with HIV (ages 50-84 at baseline). Participants were classified based on average cannabis use: frequent (> weekly) (n = 23), occasional (≤ weekly) (n = 83), and non-cannabis users (n=191) and were followed longitudinally for up to 10 years (average years of follow-up = 3.9). Multi-level models examined the effects of average and recent cannabis use on global cognition, global cognitive decline, and functional independence. Occasional cannabis users showed better global cognitive performance overall compared to non-cannabis users. Rates of cognitive decline and functional problems did not vary by average cannabis use. Recent cannabis use was linked to worse cognition at study visits when participants had THC+ urine toxicology-this short-term decrement in cognition was driven by worse memory and did not extend to reports of functional declines. Occasional (≤ weekly) cannabis use was associated with better global cognition over time in older adults with HIV, a group vulnerable to chronic inflammation and cognitive impairment. Recent THC exposure may have a temporary adverse impact on memory. To inform safe and efficacious medical cannabis use, the effects of specific cannabinoid doses on cognition and biological mechanisms must be investigated in older adults.
                Cover page: A longitudinal study of cannabis use and risk for cognitive and functional decline among older adults with HIV
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2019)
                Objective: Neurocognitive impairment (NCI) is a well-known complication of human immunodeficiency virus (HIV) infection and may be influenced by a number of psychological factors. We examined the relationship between NCI and mental health disorders, including posttraumatic stress disorder (PTSD), in a cohort of 189 active-duty and retired U.S. military men living with HIV. Methods: Participants completed selected modules of the Composite International Diagnostic Interview (CIDI) to ascertain the presence of PTSD, major depressive disorder, and other mental health diagnoses. We also obtained demographic data, including history of head trauma, via personal interview. NCI was assessed with a comprehensive battery of standardized neuropsychological tests. Results: The median age of study subjects was 36 years (interquartile range [IQR] 28 to 43) and median total years of education was 14 (IQR 12 to 16). NCI was diagnosed in 19% of subjects. Individuals with and without a history of PTSD were similar with respect to most HIV-related characteristics; however, the former were significantly more likely to have a prior acquired immunodeficiency syndrome (AIDS) diagnosis. In multivariate analysis, lifetime history of PTSD was independently associated with NCI (odds ration [OR] = 6.12; 95% confidence interval [CI] = 1.85, 20.27), while a history of head of trauma was negatively associated (OR = 0.37 95% CI = 0.15,0.92). Conclusions: Our findings demonstrate that PTSD is an important predictor of NCI in this U.S. military cohort. HIV-infected individuals with cognitive difficulties should be screened for mental health disorders, including PTSD, and prospective studies of the longitudinal relationship between PTSD and NCI, as well as the impact of PTSD treatment on future NCI, are warranted.
                  Cover page: Posttraumatic Stress Disorder and Neurocognitive Impairment in a U.S. Military Cohort of Persons Living with HIV
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2019)

                  Objective

                  The causes of neurocognitive and everyday functioning impairment among aging people living with HIV (PLWH) are multifactorial. Exposure to stress and trauma can result in neurocognitive deficits via activation of neurological and other biological mechanisms.

                  Method

                  PLWH (n = 122) and persons without HIV (n = 95), 35-65 years of age, completed four questionnaires that were used to generate a trauma, economic hardship (food insecurity and low socioeconomic status), and stress composite variable (TES). Participants also completed a comprehensive neuropsychological battery and standardized self-reports of activities of daily living (ADLs). We examined the independent and interactive effects of TES and HIV status on neurocognitive performance and ADL declines.

                  Results

                  PLWH had more traumatic events, more food insecurity, lower socioeconomic status, and higher perceived stress compared with HIV- individuals (all ps < .0001). Among PLWH, a higher composite TES score was associated with worse executive functioning (p = .02), worse learning (p = .02), worse working memory (p = .02), and more ADL declines (p < .0001), even after controlling for relevant demographic, psychiatric, substance use, and HIV disease covariates. On their own, individual TES components did not predict these outcomes. Conversely, no significant relationships were observed between TES and cognitive domains nor ADL declines among HIV- individuals.

                  Conclusions

                  A composite score of trauma, economic hardship, and stress was significantly associated with worse neurocognitive performance and functional declines among PLWH. These adverse experiences may contribute to neurocognitive and daily functioning difficulties commonly observed among PLWH. Longitudinal studies are needed to elucidate the relationships between economic/psychosocial adversities and cognitive/functional outcomes over time, and examine potential mediators, such as inflammatory biomarkers. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
                    Cover page: Effects of Trauma, Economic Hardship, and Stress on Neurocognition and Everyday Function in HIV
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2019)
                    HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N-acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.
                      Cover page: White matter damage, neuroinflammation, and neuronal integrity in HAND
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