Faculty Bibliography

IMPORTANCE:Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment. OBJECTIVES:To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence. DESIGN, SETTING, AND PARTICIPANTS:This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15 744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline. MAIN OUTCOMES AND MEASURES:Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ε4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status-Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia. RESULTS:In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean [SD] age at visit 1 of 57.4 [5.2] years) were identified among 15 744 participants. Black race (hazard ratio [HR], 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ε4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ε4 genotype. CONCLUSIONS AND RELEVANCE:Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

BACKGROUND: There are limited data about the extent of DSM-5 substance use disorders (SUDs) among primary care patients. METHODS: This study analyzed data from a multisite validation study of a substance use screening instrument conducted in a diverse sample of 2000 adults aged >/=18 years recruited from five primary care practices in four states. Prevalence and correlates of 12-month DSM-5 SUDs were examined. RESULTS: Overall, 75.5% of the sample used any substance, including alcohol (62.0%), tobacco (44.1%), or illicit drugs/nonmedical medications (27.9%) in the past 12 months (marijuana 20.8%, cocaine 7.3%, opioids 4.8%, sedatives 4.1%, heroin 3.9%). The prevalence of any 12-month SUD was 36.0% (mild disorder 14.2%, moderate/severe disorder 21.8%): tobacco 25.3% (mild 11.5%, moderate/severe 13.8%); alcohol 13.9% (mild 6.9%, moderate/severe 7.0%); and any illicit/nonmedical drug 14.0% (mild 4.0%, moderate/severe 10.0%). Among past 12-month users, a high proportion of tobacco or drug users met criteria for a disorder: tobacco use disorder 57.4% (26.1% mild, 31.3% moderate/severe) and any drug use disorder 50.2% (14.3% mild, 35.8% moderate/severe); a lower proportion of alcohol users (22.4%) met criteria for alcohol use disorder (11.1% mild, 11.3% moderate/severe). Over 80% of adults with opioid/heroin use disorder met criteria for a moderate/severe disorder. Younger ages, male sex, and low education were associated with increased odds of having SUD. CONCLUSION: These findings reveal the high prevalence of SUDs in primary care and underscore the need to identify and address them.

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness, with neurodegeneration in multiple sclerosis (MS) is well established. The potential relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective: To investigate the longitudinal relationship of INL volume changes with inflammatory disease activity. Methods: In this longitudinal multi-center study, spectral-domain optical coherence tomography (OCT) and clinical data were collected in 821 patients with MS, from eleven MS centres between 2010 and 2017. All patients had at least two visits (minimum follow- up of 6 months). Clinical data included EDSS score, occurring of relapses, including MS-associated optic neuritis (MSON). At each centre, automated segmentation of OCT scans was performed to obtain data on the pRNFL, GCIPL and INL. Annualized changes were calculated and generalized estimation equations were used to analyze longitudinal changes and associations with clinical measures. Results: In total, 1596 eyes from 798 patients (68.2% female), with a disease duration of 9.4 (+/-8.9) years, were included. Mean follow up duration was 2.3 years (range 0.5 to 5.2 years). Microcystic macular oedema (MMO) was present in 1.3% of eyes (20/1299 eyes). Clinical relapses other than MSON were present in 24.9% of patients, and disease progression was observed in 30.1%. In eyes with an episode of MSON during follow-up (N=61/1584), INL volume showed a significant increase over time (DELTAINL=0.01 mm3, p< 0.001), whereas in eyes without MSON during followup, no significant change in INL was observed (DELTAINL=0.00, p=0.308). Increase in INL volume in MSON eyes was related to a decrease in GCIPL volume (beta=-2.6, p=0.006). In eyes with MMO, the INL volume at the last visit was 0.06 mm3 higher compared to eyes without (p=0.003). There was no significant association between clinical relapses other than MSON, and INL volume changes (DELTAINL=0.00 mm3, p=0.773). Likewise, an in-or decrease in INL volume was independent of change of the EDSS score (OR=1.16, p=0.293, 95% CI 0.88-1.52). Conclusion: Our data demonstrate that an increase of the INL volume is associated with adjacent inflammation of the optic nerve and retina, but not with global physical disability. Therefore INL volume changes may be considered as a secondary outcome measure for anti-inflammatory treatment in MSON trials