We did not ask about prescribed medications and could not report on the role of polypharmacy. We conducted the study in the San Francisco Bay Area, where 67% of people experiencing homelessness live unsheltered, compared to 5% in both New York and Boston.Studies in cities with lower proportions of unsheltered homelessness may report lower rates of falls. Among individuals who are unsheltered, there are a wide variety of environments that may affect fall risk. We did not have detailed data on the variety of environments in which unsheltered homeless people stayed and cannot assess the risk of these different exposures. Alcohol consumption, particularly heavy use, is prevalent among PWH with rising rates of consumption in older PWH . To date, most studies in older PWH have focused on the combined presence of heavy alcohol use and HIV disease as risk factors for mortality and the development of age-related, multi-system comorbidities . With respect to neurobehavioral health, there is evidence that heavy alcohol use compounds HIV-related neurotoxicity , thereby impairing higher-order neurocognitive abilities critical for daily functioning . Despite the known adverse neurocognitive effects of heavy alcohol use among older PWH, it is poorly understood whether lower levels of alcohol use similarly increase risk for neurocognitive impairment or, conversely, confer a degree of neuroprotection as has been proposed in prior studies of HIV-seronegative adults . [Note: Definitions of light, moderate and heavy drinking have been arbitrarily characterized across the literature; therefore, we are using “low-risk” henceforth to represent less than heavy alcohol consumption] . The evidence supporting protective effects of alcohol, suggests an inverted J-shaped association between levels of alcohol consumed and risk for a multitude of diseases ,cannabis drying such that there is a higher risk among heavy drinkers and abstainers compared to those with low-risk alcohol consumption .
The existing literature examining the association between alcohol consumption and neurocognition among HIV- adults also suggests an inverted Jshaped association, such that low-risk alcohol consumption is associated with better neurocognition than alcohol abstinence, and heavy consumption is associated with the worst neurocognition compared to both no consumption and low-risk consumption . A longitudinal study using the UK Biobank found, among middle and older aged adults, a significant curvilinear association between alcohol consumption and neurocognition. Specifically, neurocognitive performance improved with increased alcohol use, up to one standard drink per day, at which point performance worsened . Results of studies examining this curvilinear association, however, have been inconsistent. Conflicting evidence suggests a positive linear association between neurocognition and alcohol consumption, rather than a curvilinear association . Previous literature suggests that neurocognitive deficits increase with heavier alcohol consumption among older adults . Furthermore, Parsons and Nixon suggest a potential threshold-effect, such that the deleterious effects of alcohol only occur after a specific threshold of consumption ; with heightened effects occurring at heavier levels of alcohol consumption . These inconsistent findings between a curvilinear, linear, and threshold association between alcohol consumption and neurocognition could result from confounding effects of other medical comorbidities, socioeconomic factors, and past alcohol use among current alcohol abstainers, that could contribute more strongly to neurocognitive deficits . The putative multi-system benefits of low-risk alcohol consumption in HIV- individuals have not been systematically investigated among PWH. Results of earlier studies suggest elevated rates of alcohol use among PWH while more recent reports show similar rates compared to the general population . The majority of alcohol-focused research among PWH has focused on the detrimental effects of heavy drinking or alcohol use disorders . For example, research has consistently shown combined detrimental effects of heavy drinking and HIV disease on neurocognitive function as well as gray and white matter integrity, with the worst outcomes among the heaviest drinkers .
Considering that majority of PWH do not report heavier drinking compared to the general population , there is a need for a more comprehensive understanding of the impact of low-risk alcohol consumption among PWH. Examination of whether low-risk drinking exerts differential neurocognitive effects based on HIV serostatus is particularly salient given the increasingly popular recommendations for older adults to follow certain nutritional guidelines . Given that HIV disease can enhance vulnerability to physiological damage from environmental stressors , there may be no level of alcohol associated with better neurocognitive functioning among PWH. Advancing age is independently associated with a higher risk of neurocognitive and neurode generative diseases including Alzheimer’s Disease and its precursor mild cognitive impairment . Despite use of combination antiretroviral therapy, older PWH remain particularly vulnerable to HIV-associated neurocognitive impairment and neurode generative diseases associated with aging . Considering alcohol consumption is common among PWH, and with advancing age these persons are at a heightened risk for neurocognitive impairment, the present study examined associations between the non-linear effect of recent low-risk alcohol consumption and HIV status on global and domain-specific neurocognitive outcomes. Within the range of low-risk drinking, we hypothesize a curvilinear association between recent alcohol consumption and neurocognition among HIV- individuals, such that intermediate levels of low-risk drinking will be associated with better neurocognitive function compared to non-drinkers and heavier levels; however, we do not expect this curvilinear association among PWH.Participants included 310 PWH and 89 HIV- older adults enrolled in NIH funded research studies at the University of California, San Diego HIV Neurobehavioral Research Program from 2003-2016. Participants were recruited from the greater San Diego area by the HNRP. Regulatory approval was obtained from the University of California San Diego Institutional Review Board prior to the start of protocol implementation. We have previously published several papers using other aspects of these data including medication adherence, age of first alcohol use, and neurocognitive function .
The current study represents a secondary analysis of baseline alcohol use and neurobehavioral data from the HNRP. Exclusion criteria for the current analysis included 1) self-reported current or past diagnosis of a psychotic or mood disorder with psychotic features; 2) presence of a neurological condition that could impair neurocognitive function ; 3) positive urine toxicology for illicit drugs or evidence of alcohol intoxication by Breathalyzer test on the day of testing; 4) current diagnosis of AUD; 5) current diagnosis of non-alcohol substance use disorders ; 6) recent “at risk” alcohol consumption as defined per the National Institute on Alcohol Abuse and Alcoholism criteria for “at risk” drinking ; and 7) aged 49 years and younger. The UCSD Institutional Review Board approved this study,grow trays and all participants provided written informed consent to participate. Neuromedical Evaluation All participants completed comprehensive medical evaluations and were tested for HIV by enzyme-linked immunosorbent assay . A Western Blot confirmed positive results. Reverse transcriptase-polymerase chain reaction tested levels of HIV viral load in plasma . Psychiatric, Alcohol, and Substance Use Evaluation Current and lifetime mood and substance use disorders were assessed via The Composite International Diagnostic Interview , a fully-structured, computer-based interview . Diagnoses were made in accordance with DSM-IV criteria, as the parent grants from which baseline data were collected were funded before the DSM 5 was published. DSM-IV criteria for alcohol abuse are met when participants report continued alcohol use despite recurring problems . DSM-IV criteria for alcohol dependence are met when participants endorse symptoms of tolerance, withdrawal, and impaired control over drinking . AUD was assigned when DSM-IV criteria for alcohol abuse or dependence was met in order to maintain consistency with DSM 5 criteria and nomenclature. Recent alcohol use was assessed via the HNRP Substance Use History form. This form is a modified timeline follow-back measure that assesses alcohol use metrics including the quantity and frequency of alcohol use in the last 30 days . The variable capturing the total number of drinks consumed in the last 30 days was calculated by multiplying the daily rate of alcohol consumption by the number of consumption days in the last 30 days . Total number of drinks consumed in the last 30 days will be hereafter referred to as total drinks.
Participants who reported no recent alcohol consumption were included in analyses as alcohol abstainers, with total drinks coded as 0. Neuropsychological Battery Participants were administered a well-validated, comprehensive battery of neuropsychological tests designed in accordance with the international consensus conference recommendations for HIV-associated Neurocognitive Disorders . The battery assesses seven neurocognitive domains: verbal fluency, executive function, processing speed, learning, delayed recall, working memory, and motor skills. Individual test raw scores were converted into demographically-adjusted Tscores , which were then averaged across the entire battery and within each domain to derive mean global and domain-specific T-scores, respectively . HIV group differences on demographic, psychiatric, neurocognitive, and alcohol use characteristics were compared using independent t-tests, Wilcoxon tests, and Chi-square statistics as appropriate. Separate multiple linear regressions examined the interaction between the quadratic effects of total drinks and HIV status on global and domain-specific T-scores. Demographic variables that significantly differed by HIV status at a p < .05 threshold were included as covariates. Considering the high prevalence of lifetime AUD in both persons with and without HIV, lifetime AUD was included as a covariate. Additionally, diagnosis of a lifetime non-alcohol substance use disorder was included as a covariate to account for potential confounding effects of non-alcohol substance use on neurocognitive outcomes. A follow-up analysis was conducted for any model that did not reveal a significant or trend-level interaction term between the quadratic effect of total drinks and HIV status. The follow-up analysis examined the interaction between the linear effect of total drinks and HIV status on domain-specific T-scores, covarying for demographic variables included in primary regression analyses. As a secondary followup analysis, the independent effects of total drinks and HIV status were examined for any model that did not show a significant interaction term , covarying for the same demographic variables in primary regression analyses. Regression analyses were performed using JMP Pro version 14.0.0 . Exploratory analyses, stratified by HIV status, employed the Johnson-Neyman technique to identify specific regions along the quadratic curve of total drinks at which total drinks had a statistically significant effect on neurocognition . Compared to simple slope analyses that describe quadratic effects based on how the effect of a predictor changes at different levels of that predictor, the J-N technique computes the full range of values for which the predictor slope is statistically significant. These boundaries are referred to as regions of significance. Region of significance analyses were computed using the jtools package in R statistical software . Considering long-term heavy alcohol use may have ongoing neurocognitive effects, an additional exploratory analysis examined the association between lifetime history of AUD and alcohol abstinence using a Chi-squared statistic. Finally, we explored the associations between HIV disease characteristics and global neurocognitive function using independent t-tests. We have included any significant variables as covariates in the linear regression analysis by HIV-serostatus. These analyses were performed using JMP Pro version 14.0.0 .Results of linear regressions examining the interaction between the quadratic effect of total drinks and HIV status on neurocognitive outcomes are presented in Table 2. In these adjusted models, the interaction between the quadratic effect of total drinks and HIV status was significant for global function , executive function , learning , delayed recall , and motor skills . With respect to covariates, older age, a lifetime history of MDD, and a lifetime history of a non-alcohol substance use disorder were associated with worse neurocognitive performance across multiple domains. Follow-up analyses were conducted to examine the interaction between the linear effect of total drinks and HIV status on neurocognitive outcomes that showed no significant or trend-level interaction term . Similar adjusted linear regression models revealed no significant interaction effects between total drinks and HIV status on domain specific neurocognition . To further examine the independent effects of total drinks and HIV status on neurocognition, linear regression models examined the effects of HIV status, total drinks, and covariates from previous models on neurocognitive outcomes . In these adjusted models, HIV status was significantly associated with verbal fluency , processing speed , and working memory , such that PWH performed significantly worse than their HIV- counterparts.Additional follow-up analyses on domains that revealed significant quadratic associations were stratified by HIV serostatus .