A Preliminary Study of Stress, Mental Health, and Pain Related to the COVID-19 Pandemic and Odds of Persistent Prescription Opioid Use.

BACKGROUND: The COVID-19 pandemic has been associated with increased opioid prescribing. It is not known if perceived COVID-19 related stress is associated with increased odds of long-term opioid use. OBJECTIVE: To determine if greater COVID-19-related stress and worsening pain attributed to the pandemic was associated with LTOT over a 6-month observation period. DESIGN: Longitudinal cohort. PARTICIPANTS: Patients (n=477) from two midwestern health care systems, with any acute or chronic non-cancer pain, starting a new period of 30-90-day prescription opioid use, were invited to participate in the Prescription Opioids and Depression Pathways Cohort Study, a longitudinal survey study of pain, opioid use, and mental health outcomes. MAIN MEASURES: Baseline and 6-month follow-up assessments were used to measure the association between perceived COVID-19 stressors, the perception that pain was made worse by the pandemic and the odds of persistent opioid use, i.e., remaining a prescription opioid user at 6-month follow-up. Multivariate models controlled for demographics, opioid dose, and change in pain characteristics, mental health measures, and social support. KEY RESULTS: Participants were, on average, 53.9 (±11.4) years of age, 67.1% White race, and 70.9% female. The most frequently endorsed COVID-19 stressor was "worry about health of self/others" (85.7% endorsed) and the least endorsed was "worsened pain due to pandemic" (26.2%). After adjusting for all covariates, "worsened pain due to pandemic" (OR=2.88; 95%CI: 1.33-6.22), change in pain interference (OR=1.20; 95%CI: 1.04-1.38), and change in vital exhaustion (OR=0.90; 95%CI: 0.82-0.99) remained significantly associated with persistent opioid use. CONCLUSIONS: Patients who attribute worsening pain to the COVID-19 pandemic are more likely to be persistent opioid users. Further research is warranted to identify mechanisms underlying this association. Clinicians may consider discussing pain in the context of the pandemic to identify patients at high risk for persistent opioid use.

"I really had somebody in my corner." Patient experiences with a pharmacist-led opioid tapering program.

BACKGROUND: Opioid tapering has been identified as an effective strategy to prevent the dangers associated with long-term opioid therapy for patients with chronic pain. However, many patients are resistant to tapering, and conversations about tapering can be challenging for health care providers. Pharmacists can play a role in supporting both providers and patients with the process of opioid tapering. OBJECTIVE: Qualitatively describe patient experiences with a unique phone-based and pharmacy-led opioid tapering program implemented within an integrated health care system. METHODS: In-depth telephone interviews with patients who completed the program were recorded, transcribed, and analyzed. Themes were identified through a constant comparative approach. RESULTS: We completed 25 interviews; 80% of patients were women (20), with a mean age of 58 years, and 72% (18) had been using opioids for pain management for 10 or more years. Most (60%) described a positive and satisfying experience with the tapering program. Strengths of the program reported by patients included a patient-centered and compassionate taper approach, flexible taper pace, easy access to knowledgeable pharmacist advocates, and resultant improvements in quality of life (e.g., increased energy). Challenges reported included: unhelpful or difficult-to-access nonpharmacological pain management options, negative quality of life impacts (e.g., inability to exercise), and lack of choice in the taper process. At the end of tapering, most patients (72%) described their pain as reduced or manageable rather than worse and expressed willingness to use the program in the future if a need should arise. CONCLUSIONS: Patients in a pharmacist-led opioid tapering program appreciated the program's individualized approach to care and access to pharmacist' expertise. Most interviewed patients successfully reduced their opioid use and recommended that the program should continue as an offered service. To improve the program, patients suggested increased personalization of the taper process and additional support for withdrawal symptoms and nonpharmacological pain management.

Development of High-Risk Geriatric Polypharmacy Electronic Clinical Quality Measures and a Pilot Test of EHR Nudges Based on These Measures.

BACKGROUND: Inappropriate polypharmacy, prevalent among older patients, is associated with substantial harms. OBJECTIVE: To develop measures of high-risk polypharmacy and pilot test novel electronic health record (EHR)-based nudges grounded in behavioral science to promote deprescribing. DESIGN: We developed and validated seven measures, then conducted a three-arm pilot from February to May 2019. PARTICIPANTS: Validation used data from 78,880 patients from a single large health system. Six physicians were pre-pilot test environment users. Sixty-nine physicians participated in the pilot. MAIN MEASURES: Rate of high-risk polypharmacy among patients aged 65 years or older. High-risk polypharmacy was defined as being prescribed ≥5 medications and satisfying ≥1 of the following high-risk criteria: drugs that increase fall risk among patients with fall history; drug-drug interactions that increase fall risk; thiazolidinedione, NSAID, or non-dihydropyridine calcium channel blocker in heart failure; and glyburide, glimepiride, or NSAID in chronic kidney disease. INTERVENTIONS: Physicians received EHR alerts when renewing or prescribing certain high-risk medications when criteria were met. One practice received a "commitment nudge" that offered a chance to commit to addressing high-risk polypharmacy at the next visit. One practice received a "justification nudge" that asked for a reason when high-risk polypharmacy was present. One practice received both. KEY RESULTS: Among 55,107 patients 65 and older prescribed 5 or more medications, 6256 (7.9%) had one or more high-risk criteria. During the pilot, the mean (SD) number of nudges per physician per week was 1.7 (0.4) for commitment, 0.8 (0.5) for justification, and 1.9 (0.5) for both interventions. Physicians requested to be reminded to address high-risk polypharmacy for 236/833 (28.3%) of the commitment nudges and acknowledged 441 of 460 (95.9%) of justification nudges, providing a text response for 187 (40.7%). CONCLUSIONS: EHR-based measures and nudges addressing high-risk polypharmacy were feasible to develop and implement, and warrant further testing.

Depression and Long-Term Prescription Opioid Use and Opioid Use Disorder: Implications for Pain Management in Cancer.

OPINION STATEMENT: Preventing depression in cancer patients on long-term opioid therapy should begin with depression screening before opioid initiation and repeated screening during treatment. In weighing the high morbidity of depression and opioid use disorder in patients with chronic cancer pain against a dearth of evidence-based therapies studied in this population, patients and clinicians are left to choose among imperfect but necessary treatment options. When possible, we advise engaging psychiatric and pain/palliative specialists through collaborative care models and recommending mindfulness and psychotherapy to all patients with significant depression alongside cancer pain. Medications for depression should be reserved for moderate to severe symptoms. We recommend escitalopram/citalopram or sertraline among selective serotonin reuptake inhibitors (SSRIs), or the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine, venlafaxine, or desvenlafaxine if patients have a significant component of neuropathic pain or fibromyalgia. Tricyclic antidepressants (TCAs) (consider nortriptyline or desipramine, which have better anticholinergic profiles) should be considered for patients who do not respond to or tolerate SSRI/SNRIs. Existing evidence is inadequate to definitively recommend methylphenidate or novel agents, such as ketamine or psilocybin, as adjunctive treatments for cancer-related depression and pain. Physicians who treat patients with cancer pain should utilize universal precautions to limit the risk of non-medical opioid use (non-medical opioid use). Patients should be screened for non-medical opioid use behaviors at initial consultation and at regular intervals during treatment using a non-judgmental approach that reduces stigma. Co-management with an addiction specialist may be indicated for patients at high risk of non-medical opioid use and opioid use disorder. Buprenorphine and methadone are indicated for the treatment of opioid use disorder, and while they have not been systematically studied for treatment of opioid use disorder in patients with cancer pain, they do provide analgesia for cancer pain. While an interdisciplinary team approach to manage psychological stress may be beneficial, this may not be possible for patients treated outside of comprehensive cancer centers.

Characteristics of Patients with Non-Cancer Pain and Perceived Severity of COVID-19 Related Stress.

Synopsis Patients with non-cancer pain reported increased pain and pain interference during the first months of the COVID-19 pandemic. We determined if pain, prescription opioid use, and comorbidities were associated with perceived COVID-19-related stress as the pandemic peaked. Analysis of survey data revealed that depression/anxiety, pain severity, and pain interference were most strongly and consistently associated with greater stress due to COVID-19 related changes in lifestyle, worsening of emotional/mental health and worsening pain. Identifying specific stressful experiences that most impacted patients with non-cancer pain may help target public health and treatment interventions. Background: During the first months of the COVID-19 pandemic, patients with chronic pain reported increased pain severity and interference. This study measured the association between pain, prescription opioid use, and comorbidities with perceived COVID-19-related stress as the pandemic peaked in the United States. Methods: From 9/2020 to 3/2021, the first 149 subjects from a prospective cohort study of non-cancer pain, completed a survey which contained the Complementary and Integrative Research (CAIR) Pandemic Impact Questionnaire (C-PIQ). Respondents also reported whether the pandemic has contributed to their pain or opioid use. Bivariate comparisons explored patient characteristics with each CAIR domain. Results: Respondents mean age was 54.6 (±11.3) years, 69.8% were female, 64.6% were White. Respondent characteristics were not associated with reading/watching/thinking about the pandemic or with worry about health. Depression/anxiety (p=0.003), using any prescription opioid in the prior three months (p=0.009), higher morphine milligram equivalent used (p=0.005), higher pain severity (p=0.011), and higher pain interference (p=0.0004) were all positively and significantly associated with moderate to severe stress due to COVID-19 related lifestyle changes. Depression/anxiety, pain severity, and pain interference were positively associated with COVID-19-related worsening emotional/mental health. Depression/anxiety were significantly (p<0.0001) associated with reporting that the pandemic made their pain worse. Conclusion: Depression, anxiety, pain severity, and pain interference were most strongly and consistently associated with COVID-19 changes in way of life, worsening of emotional/mental health, and worsening pain. Identifying specific stressful experiences that most impacted patients with noncancer pain may inform public health and treatment interventions.

When Physical and Social Pain Coexist: Insights Into Opioid Therapy.

The US opioid epidemic challenges us to rethink our understanding of the function of opioids and the nature of chronic pain. We have neatly separated opioid use and abuse as well as physical and social pain in ways that may not be consistent with the most recent neuroscientific and epidemiological research. Physical injury and social rejection activate similar brain centers. Many of the patients who use opioid medications long term for the treatment of chronic pain have both physical and social pain, but these medications may produce a state of persistent opioid dependence that suppresses the endogenous opioid system that is essential for human socialization and reward processing. Recognition of the social aspects of chronic pain and opioid action can improve our treatment of chronic pain and our use of opioid medications.

"We Need to Taper." Interviews with Clinicians and Pharmacists About Use of a Pharmacy-Led Opioid Tapering Program.

OBJECTIVE: To identify factors that influence or interfere with referrals by primary care providers (PCPs) to a pharmacist-led telephone-based program to assist patients undergoing opioid tapering. The Support Team Onsite Resource for Management of Pain (STORM) program provides individualized patient care and supports PCPs in managing opioid tapers. DESIGN: Qualitative interviews were conducted with referring PCPs and STORM staff. Interview guides addressed concepts from the RE-AIM framework, focusing on issues affecting referral to the STORM program. SETTING: An integrated healthcare system (HCS) in the Northwest United States. SUBJECTS: Thirty-five interviews were conducted with 20 PCPs and 15 STORM staff. METHODS: Constant comparative analysis was used to identify key themes from interviews. A codebook was developed based on interview data and a qualitative software program was used for coding, iterative review, and content analysis. Representative quotes illustrate identified themes. RESULTS: Use of the STORM opioid tapering program was influenced by PCP, patient, and HCS considerations. Factors motivating use of STORM included lack of PCP time to support chronic pain patients requiring opioid tapering and the perception that STORM is a valued partner in patient care. Impediments to referral included PCP confidence in managing opioid tapering, patient resistance to tapering, forgetting about program availability, and PCP resistance to evolving guidelines regarding opioid tapering goals. CONCLUSIONS: PCPs recognized that STORM supported patient safety and reduced clinician burden. Utilization of the program could be improved through ongoing PCP education about the service and consistent co-location of STORM pharmacists within primary care clinics.

Factors associated with opioid-tapering success: A mixed methods study.

OBJECTIVE: Opioid tapering is recommended when risks of chronic opioid use outweigh benefits. Little is known about patient characteristics or factors related to tapering success. We sought to identify characteristics that predict a 50% reduction in opioid use and qualitatively characterize factors that impact tapering success. METHODS: We used multilevel hierarchical modeling to identify predictors of a 50% reduction in opioid use among Kaiser Permanente Northwest patients who underwent pharmacist-led tapering between 2012 and 2017. We conducted qualitative interviews among patients and pharmacists to identify factors influencing tapering success. RESULTS: We identified 1384 patients who, on average, were dispensed 207 milligram morphine equivalents per day at baseline. After 12 months, 56% of patients reduced their opioid use by 50%. Increased odds of 50% reduction were associated with younger age 21-49 years (Odds ratio [OR] 1.32, P = 0.004); previous surgery (OR 2.24, P < 0.001); increased number of Addiction Medicine encounters (OR 1.25, P = 0.011); substance use disorder (OR 1.62, P = 0.001); anxiety (OR 1.32, P = 0.003); non-narcotic analgesic (OR 1.22, P = 0.025) or antipsychotic medication use (OR 1.53, P = 0.006); and opioid days supplied in the previous year (OR 1.08, P < 0.001). Patients and pharmacists noted that success was influenced by patients' willingness or resistance to change opioid use, the level of patient engagement achieved through communication with their provider, aspects of the tapering process such as pace, and external factors including health issues or caregiving responsibilities. CONCLUSIONS: Over one-half of patients who underwent tapering reduced their opioid use by 50%. Patient demographic and clinical characteristics were predictive of tapering success; however, patients and pharmacists noted that patient willingness, motivation, and personal circumstances also influence tapering outcome. Opioid tapering requires an individualized approach. Both clinical factors and personal circumstances should be considered when opioid tapering is being discussed as a possible solution for a patient.

Complex Persistent Opioid Dependence with Long-term Opioids: a Gray Area That Needs Definition, Better Understanding, Treatment Guidance, and Policy Changes.

The multitude of treatments available for tens of millions of US adults with moderate/severe chronic pain have limited efficacy. Long-term opioid therapy (LTOT) is a widely available option for controlling pain among patients with chronic pain refractory to other treatments. The recent recognition of LTOT inefficacy and complications has led to more frequent opioid tapering, which in turn has revealed its own set of complications. The occurrence of the same set of symptoms-worsening pain, declining function, and clinical instability-in contrasting contexts of LTOT ineffectiveness and opioid tapering has led to increasing recognition of the utility of complex persistent opioid dependence (CPOD), a clinically distinct but biologically similar state compared with opioid use disorder as an explanatory diagnosis/heuristic. Recent guidelines for LTOT tapering have incorporated buprenorphine treatment based on CPOD concepts as a recommended treatment for problems due to opioid tapering with limited supportive evidence. The increasing utilization of buprenorphine for both LTOT ineffectiveness and opioid tapering problems raises the urgent need for a review of the clinical definition, mechanisms, and treatment of CPOD and pertinent policies. In this manuscript, we discuss various issues related to CPOD that requires further clarification through research and policy development.

A Research Agenda for Advancing Strategies to Improve Opioid Safety: Findings from a VHA State of the Art Conference.

US military Veterans have been disproportionately impacted by the US opioid overdose crisis. In the fall of 2019, the Veterans Health Administration (VHA) convened a state-of-the-art (SOTA) conference to develop research priorities for advancing the science and clinical practice of opioid safety, including both use of opioid analgesics and managing opioid use disorder. We present the methods and consensus recommendations from the SOTA. A core group of researchers and VA clinical stakeholders defined three areas of focus for the SOTA: managing opioid use disorder, long-term opioid therapy for pain including consideration for opioid tapering, and treatment of co-occurring pain and substance use disorders. The SOTA participants divided into three workgroups and identified key questions and seminal studies related to those three areas of focus. The strongest recommendations included testing implementation strategies in the VHA for expanding access to medication treatment for opioid use disorder, testing collaborative tapering programs for patients prescribed long-term opioids, and larger trials of behavioral and exercise/movement interventions for pain among patients with substance use disorders.

Outcomes in Long-term Opioid Tapering and Buprenorphine Transition: A Retrospective Clinical Data Analysis.

BACKGROUND: There are significant medical risks of long-term opioid therapy (LTOT) for chronic pain. Consequently, there is a need to identify effective interventions for the reduction of high-dose full-agonist opioid medication use. METHODS: The current study details a retrospective review of 240 patients with chronic pain and LTOT presenting for treatment at a specialty opioid refill clinic. Patients first were initiated on an outpatient taper or, if taper was not tolerated, transitioned to buprenorphine. This study analyzes potential predictors of successful tapering, successful buprenorphine transition, or failure to complete either intervention and the effects of this clinical approach on pain intensity scores. RESULTS: One hundred seven patients (44.6%) successfully tapered their opioid medications under the Centers for Disease Control and Prevention guideline target dose (90 mg morphine-equianalgesic dosage), 45 patients (18.8%) were successfully transitioned to buprenorphine, and 88 patients (36.6%) dropped out of treatment: 11 patients during taper, eight during buprenorphine transition, and 69 before initiating either treatment. Conclusions. Higher initial doses of opioids predicted a higher likelihood of requiring buprenorphine transition, and a co-occurring benzodiazepine or z-drug prescription predicted a greater likelihood of dropout from both interventions. Patterns of change in pain intensity according to treatment were mixed: among successfully tapered patients, 52.8% reported greater pain and 23.6% reported reduced pain, whereas 41.8% reported increased pain intensity and 48.8% reported decreased pain after buprenorphine transition. Further research is needed on predictors of treatment retention and dropout, as well as factors that may mitigate elevated pain scores after reduction of opioid dosing.

Impact of adherence to antidepressants on long-term prescription opioid use cessation.

BACKGROUND: Depression contributes to persistent opioid analgesic use (OAU). Treating depression may increase opioid cessation. Aims To determine if adherence to antidepressant medications (ADMs) v. non-adherence was associated with opioid cessation in patients with a new depression episode after >90 days of OAU. METHOD: Patients with non-cancer, non-HIV pain (n = 2821), with a new episode of depression following >90 days of OAU, were eligible if they received ≥1 ADM prescription from 2002 to 2012. ADM adherence was defined as >80% of days covered. Opioid cessation was defined as ≥182 days without a prescription refill. Confounding was controlled by inverse probability of treatment weighting. RESULTS: In weighted data, the incidence rate of opioid cessation was significantly (P = 0.007) greater in patients who adhered v. did not adhered to taking antidepressants (57.2/1000 v. 45.0/1000 person-years). ADM adherence was significantly associated with opioid cessation (odds ratio (OR) = 1.24, 95% CI 1.05-1.46). CONCLUSIONS: ADM adherence, compared with non-adherence, is associated with opioid cessation in non-cancer pain. Opioid taper and cessation may be more successful when depression is treated to remission. Declaration of interest None.

Factors Associated with Opioid Initiation in OEF/OIF/OND Veterans with Traumatic Brain Injury.

Objective: These analyses examined opioid initiation and chronic use among Iraq (OIF) and Afghanistan (OEF/OND) veterans with a new diagnosis of traumatic brain injury (TBI) in the Veterans Health Administration (VHA). Methods: Data were obtained from national VHA data repositories. Analyses included OEF/OIF/OND veterans with a new TBI diagnosis in 2010-2012 who used the VHA at least twice, had not received a VHA opioid prescription in the 365 days before diagnosis, and had at least 365 days of data available after TBI diagnosis. Results: Analyses included 35,621 veterans. Twenty-one percent initiated opioids; among new initiators, 23% used chronically. The mean dose was 24.0 mg morphine equivalent dose (MED) daily (SD = 24.26); mean days supplied was 60.52 (SD = 74.69). Initiation was significantly associated with age 36-45 years (odds ratio [OR] = 1.09, 95% CI = 1.01-1.17, P = 0.04), female gender (OR = 1.22, P < 0.001), having back pain (OR = 1.38, P < 0.0001), arthritis/joint pain (OR = 1.24, P < 0.0001), or neuropathic pain (OR = 1.415, P < 0.02). In veterans age 36-45 years, those living in small rural areas had higher odds of chronic opioid use (OR = 1.31, P < 0.0001, and OR = 1.33, P = 0.006, respectively) and back pain (OR = 1.36, P = 0.003). Headache/migraine pain was associated with decreased odds of chronic opioid use (OR = 0.639, P = 0.003). Conclusions: Prevalence of opioid use is relatively low among OEF/OIF/OND veterans with newly diagnosed TBI who are using VHA. Among those who initiated opioids, about 25% use them chronically. Prescribing was mostly limited to moderate doses, with most veterans using opioids for approximately two months of the 12-month study period.

ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial.

AIMS/HYPOTHESIS: The Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, a double 2x2 factorial parallel-group randomised clinical trial, tested whether intensive compared with standard management of hyperglycaemia, BP or lipid levels reduced cognitive decline and brain atrophy in 2977 people with type 2 diabetes. We describe the results of the observational extension study, ACCORDION MIND (ClinicalTrials.gov registration no. NCT00182910), which aimed to measure the long-term effects of the three ACCORD interventions on cognitive and brain structure outcomes approximately 4 years after the trial ended. METHODS: Participants (mean diabetes duration 10 years; mean age 62 years at baseline) received a fourth cognitive assessment and a third brain MRI, targeted at 80 months post-randomisation. Primary outcomes were performance on the Digit Symbol Substitution Test (DSST) and total brain volume (TBV). The contrast of primary interest compared glycaemic intervention groups at the ACCORDION visit; secondary contrasts were the BP and lipid interventions. RESULTS: Of the surviving ACCORD participants eligible for ACCORDION MIND, 1328 (68%) were re-examined at the ACCORDION follow-up visit, approximately 47 months after the intensive glycaemia intervention was stopped. The significant differences in therapeutic targets for each of the three interventions (glycaemic, BP and lipid) were not sustained. We found no significant difference in 80 month mean change from baseline in DSST scores or in TBV between the glycaemic intervention groups, or the BP and lipid interventions. Sensitivity analyses of the sites with ≥70% participation at 80 months revealed consistent results. CONCLUSIONS/INTERPRETATION: The ACCORD interventions did not result in long-term beneficial or adverse effects on cognitive or brain MRI outcomes at approximately 80 months follow-up. Loss of separation in therapeutic targets between treatment arms and loss to follow-up may have contributed to the lack of detectable long-term effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00182910.

Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus.

BACKGROUND: Relationships between early kidney disease, neurocognitive function, and brain anatomy are poorly defined in African Americans with type 2 diabetes mellitus (T2DM). STUDY DESIGN: Cross-sectional associations were assessed between cerebral anatomy and cognitive performance with estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) in African Americans with T2DM. SETTING & PARTICIPANTS: African Americans with cognitive testing and cerebral magnetic resonance imaging (MRI) in the African American-Diabetes Heart Study Memory in Diabetes (AA-DHS MIND; n=512; 480 with MRI) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) MIND (n=484; 104 with MRI) studies. PREDICTORS: eGFR (CKD-EPI creatinine equation), spot UACR. MEASUREMENTS: MRI-based cerebral white matter volume (WMV), gray matter volume (GMV), and white matter lesion volume; cognitive performance (Mini-Mental State Examination, Digit Symbol Coding, Stroop Test, and Rey Auditory Verbal Learning Test). Multivariable models adjusted for age, sex, body mass index, scanner, intracranial volume, education, diabetes duration, hemoglobin A1c concentration, low-density lipoprotein cholesterol concentration, smoking, hypertension, and cardiovascular disease were used to test for associations between kidney phenotypes and the brain in each study; a meta-analysis was performed. RESULTS: Mean participant age was 60.1±7.9 (SD) years; diabetes duration, 12.1±7.7 years; hemoglobin A1c concentration, 8.3%±1.7%; eGFR, 88.7±21.6mL/min/1.73m2; and UACR, 119.2±336.4mg/g. In the fully adjusted meta-analysis, higher GMV associated with lower UACR (P<0.05), with a trend toward association with higher eGFR. Higher white matter lesion volume was associated with higher UACR (P<0.05) and lower eGFR (P<0.001). WMV was not associated with either kidney parameter. Higher UACR was associated with lower Digit Symbol Coding performance (P<0.001) and a trend toward association with higher Stroop interference; eGFR was not associated with cognitive tests. LIMITATIONS: Cross-sectional; single UACR measurement. CONCLUSIONS: In African Americans with T2DM, mildly high UACR and mildly low eGFR were associated with smaller GMV and increased white matter lesion volume. UACR was associated with poorer processing speed and working memory.