HOPE HOME staff collected data on alcohol use, drug use, and depression using validated scales in their 6-month followup visits. We used the closest score to our neurologic assessment and excluded individuals with assessments more than 4 weeks after our neurologic exam. The HOPE HOME staff used the Alcohol Use Disorders Identification Test to assess for alcohol use disorders. HOPE HOME modified the AUDIT by asking about behaviors in the past 6 months, instead of past year. We considered scores of 8–15 as measures of harmful alcohol use, 16–19 as moderate disorders, and 20 and above as evidence of severe alcohol use disorders. HOPE HOME staff also adapted questions from World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test which assesses drug use in the 12 months prior to survey administration to assess drug use in the past 6 months. We asked participants how often they used, had a strong desire or urge to use, experienced health, social, legal or financial problems as a result of using, and failed to do what was normally expected of them due to using the following substances: cannabis, cocaine, amphetamine type stimulants, inhalants, sedatives or sleeping pills, hallucinogens, opioids, or other drugs in the past 6 months. Possible responses were the following: never , once or twice , monthly , weekly , and daily or almost daily . HOPE HOME asked participants if a friend, relative, or anyone else had ever expressed concern about their drug use for the listed substances and if they ever tried and failed to control, cut down, or stop using each listed drug. Possible responses were never , in the past 6 months , and not in the past 6 months . For each substance, we specified substance involvement risk as lower risk , moderate risk , and high risk . HOPE HOME used the Center for Epidemiologic Studies Depression Scale to assess depression in participants, which has shown to be a reliable measure of depression in homeless populations. We asked participants if they experienced various feelings or behaviors rarely ,drying cannabis some or a little of the time , occasionally or a moderate amount of time , or most or all of the time .
We asked participants about the following experiences: being bothered by things they usually aren’t bothered by, poor appetite, not being able to shake off the blues even with help from family/friends, feeling just as good as other people, having trouble keeping his/her mind on task, feeling depressed, feeling like everything is an effort, feeling hopeful about the future, thinking his/her life had been a failure, fear, restless sleep, happiness, talking less than usual, loneliness, feeling that people were unfriendly, enjoying life, crying spells, sadness, feeling that people disliked him/her, feeling that he or she could not get “going.” Scores of 0–3 for each of the 20 questions were combined for a total score of up to 60. We used a standard threshold score of 16 or more to categorize possible clinical depression. Neurologists [SM and SL] conducted structured neurocognitive histories in all study participants through a phone interview. This included participants’ age, sex, self-reported race, educational attainment, and work experience/stated profession. We also screened participants for comorbidities that are known risk factors for NDDB and/or cognitive decline: traumatic brain injury , stroke/transient ischemic attack, seizures/epilepsy, encephalitis/meningitis, sleep disorders , hypertension, hypercholesterolemia, obesity, diabetes, hearing loss, vision loss, cardiovascular disease, and thyroid disorders . Along with formalized scores for measuring alcohol use and drug use , we obtained informal data on individuals’ use, we defined remote alcohol and illicit drug use as no use within the previous year . We screened for the presence of known specific neurodegenerative disorders among first- and second-degree relatives . We asked the following question to elicit any other pertinent family history from each participant: “Did anyone in your family, including grandparents, parents, aunts or uncles, cousins, brothers or sisters, or children experience progressive loss of mental functions, or thinking abilities, or cognitive functions? Progressive changes in personality or behavior? Progressive difficulties speaking? Progressive difficulties using their arms and legs?” We [SM and/or SL] then assessed each participant’s neurocognitive history following a structured interview based on gold standard evaluation procedures in the UCSF ADRC. Participants were asked to report on perceived changes to their neurocognitive health over the previous “few years” compared to their perceived baseline.
The interview began with a brief assessment of subjective cognitive decline based on a previously published SCD interview, the SCDI . This interview begins with an open-ended question, followed by a brief structured assessment of changes to individual cognitive domains and an assessment of when said cognitive changes began, whether or not the participant felt concerned about said cognitive changes , and if the participant sought medical care for said complaints. This initial assessment was followed by a detailed neurocognitive review of systems that probed the following domains: episodic memory , visuospatial skills , executive function , language , sleep, autonomic, and sensory functions, motor function , and behavioral and emotional processing changes. Participants were scheduled for in-person neurological examinations after completing their phone-based neurocognitive history examinations. Experienced neurologists [SM or SL] performed neurologic examinations in a safe and private outdoor space within the HOPE-HOME study site in Oakland, California. Neurological examinations were conducted using Personal Protective Equipment in accordance with COVID-19 public health recommendations. In addition to all components of a gold standard bedside neurological examination we assessed olfaction using the Brief Smell Identification Test given that hyposmia/anosmia is a known risk factor for NDDB, especially alpha-synuclein associated disease .Trained testers [SM or GA] conducted all neuropsychologic assessments, which were administered on the UCSF Tabletbased Cognitive Assessment Tool platform . The tests were developed and validated by UCSF neuropsychologists to measure cognitive skills that are affected by typical and atypical presentations of NDDB . Participants were asked to report any drug use prior to test administration and were assessed for clinical signs of intoxication. If participants screened positive, they were rescheduled for a different visit. None of the participants in this study showed clinical signs of intoxication during testing. Memory was assessed using Favorites, an associative memory test that requires participants to learn associations between verbal and visual stimuli.
Performance was summarized by the total correct across the 2 learning and 1 delay trials. Executive functions were assessed by Match, which requires participants to quickly match numbers and simple pictures. Performance was summarized by total correct in 2 min. Flanker and Dot Counting tests from the NIH EXAMINER battery provided additional executive assessments . Visuospatial skills was measured by Line Orientation, which requires participants to indicate which of two lines is parallel to a target line. Language was assessed by Animal Fluency . Social cognition was assessed with the Dynamic affect Recognition Test on which participants are asked to identify the emotion expressed in each of a series of short videos relying on nonverbal cues. In total, administration of the TabCAT spanned 30–45 min . Participants’ scores on neuropsychological testing were adjusted for demographic factors using normative data . For Favorites, Match, Line Orientation, and Animal Fluency,ebb flow the scores were corrected for age and education level using a previously published regression approach . Flanker and Dot Counting were corrected for age and sex using the same method. DART was corrected for sex and age using a traditional box norms approach. As the participant sample is disadvantaged relative to reference samples, a conservative impairment threshold was selected. Using the summation of data obtained from structured neurocognitive history, neurological examination, neuropsychological examination, and functional assessment, we assigned each participant into one of four groups to denote each participant’s overall neurocognitive health status: neurocognitively normal, SCD , and mild or major neurocognitive disorder based on criteria from the 5th version of the Diagnostic and Statistical Manual . “Neurocognitively normal” participants were those that did not report or endorse neurocognitive concerns based on our neurocognitive history intake, performed within normal range on neuropsychological examination, and reported intact ADLs and iADLs. Participants with SCD were those who reported and/or endorsed neurocognitive concerns on our neurocognitive history intake but performed within normal range on neuropsychological examination and reported intact ADLs and iADLs. Participants with mild neurocognitive disorder were those who reported and/or endorsed neurocognitive concerns on our neurocognitive history intake and performed below expected on neuropsychological examination yet reported intact ADLs and iADLs. Finally, participants with major neurocognitive disorder were those who reported and/or endorsed neurocognitive concerns on our neurocognitive history intake, performed below expected on neuropsychological examination, and reported significant impairments on their ADLs and/or iADLs.
Subsequently, we screened all neurocognitive signs and symptoms obtained from structured neurocognitive history, neurological examination, neuropsychological examination, and functional assessment, to assign each participant into one or more of the gold standard research diagnostic criteria for NDDB, which included the following criteria: possible Alzheimer’s Dementia , possible behavioral variant frontotemporal dementia , probable corticobasal syndrome , possible CBS, possible Lewy body dementia , amnestic mild cognitive impairment , nonamnestic MCI, possible multiple system atrophy , primary progressive aphasia , possible Parkinson’s disease , possible progressive supranuclear palsy , suggestive PSP, and posterior cortical atrophy . In this manner, we explored possible etiologic diagnoses for the observed neurocognitive deficits observed in participants based solely on clinical data. Lifetime risks for alcohol-related blackouts in many surveys is >50% among drinkers . The high blood alcohol concentrations involved and the compromised cognitive processes inherent in ARBs increase risks for additional serious consequences, including accidents, unwanted sex, and exposure to other forms of violence . In addition to BACs>.20g/dl needed for most blackouts, ARBs are also associated with European American [EA] ancestry, female sex, and several genetically-influenced phenotypes related to heavier drinking, including a low level of response to alcohol, as described further below . However, the relationships among these characteristics and ARBs are complex and their potential interactions have not been adequately evaluated . The link of ethnicity to ARBs may relate to heavier drinking in EAs and, potentially, Hispanics, compared to other populations such as Asian individuals . Ethnic differences may also reflect divergent patterns of alcohol metabolizing enzymes, as Asians have higher rates of mutations in both aldehyde dehydrogenase and alcohol dehydrogenase that produce greater alcohol sensitivities and contribute to lower levels of heavier drinking with subsequent lower rates of ARBs . EAs, Asians, and Hispanics also differ on cultural-based proscriptions against heavy drinking, especially in women , have different rates of low LRs unrelated to alcohol metabolism , and vary regarding typical body mass indices, with the latter likely to affect BACs per drink .This reflects women’s likely lower body weight, less first pass metabolism of alcohol, and higher body fat with corresponding less body water per pound. However, there is overlap between ethnic background and drinking patterns among women, and it is not clear if those two characteristics interact regarding ARBs. Both ethnicity and sex also relate to low LRs to alcohol . However, LR differences across EA, Hispanic, and Asian individuals , and across sexes raise questions about how LR interacts with ethnicity and sex to contribute to ARBs.A recent review highlighted the paucity of prospective studies evaluating how multiple risk factors interact in contributing to ARBs, while controlling for alcohol quantities . In response, the present analyses extracted information from a 55-week prospective study that evaluated educational approaches to preventing heavy drinking on campus . The data tested four hypotheses: Hypothesis 1 states that relationships of ethnicity to ARBs will remain even after controlling for the maximum number of drinks consumed, with the highest ARB prevalence in EA and Hispanic and the lowest rates in Asian students. Hypothesis 2 is that ARB rates will be higher in females, and that the ethnic differences will remain robust after considering sex and controlling for maximum drinks. Hypothesis 3 proposes that low LRs will relate to ARBs, and that ethnic differences will remain even after considering maximum drinks and LR. Hypothesis 4 states that ethnic group status will interact with sex and LR to predict rates of ARBs over 55 weeks.Following University of California, San Diego Human Protections Committee approval, in January, 2014, 18-year-old freshmen were selected from respondents to questionnaires emailed to UCSD students to solicit participants for a 55-week study of ways to diminish heavy drinking in college students .