Background and Purpose-Cognitive dysfunction occurs in 9% to 23% of patients during the first month after carotid endarterectomy (CEA). A 4-basepair (AAAT) tandem repeat polymorphism (either 3 or 4 repeats) has been described in the promoter region of inducible nitric oxide synthase (iNOS), a gene with complex roles in ischemic injury and preconditioning against ischemic injury. We investigated whether the 4-repeat variant (iNOS ϩ ) affects the incidence of cognitive dysfunction after CEA. Methods-One-hundred eighty-five CEA and 60 spine surgery (control) subjects were included in this nested cohort analysis. Subjects underwent a battery of 7 neuropsychometric tests before and 1 day and 1 month after surgery. Multivariate logistic regression analyses were performed to determine if the iNOS promoter variant was independently associated with the incidence of cognitive dysfunction at 1 day and 1 month. Further, all right-hand-dominant CEA subjects were grouped by operative side and performance on each test was compared between iNOS ϩ and iNOS Ϫ groups. Results-Forty-four of 185 CEA subjects had at least 1 iNOS promoter allele containing 4 copies of the tandem repeat (iNOS

BACKGROUND/OBJECTIVE Regular physical activity (PA) has been associated with improved cognitive function, but its effect on postoperative delirium (POD) has not been established. Our objectives were to determine the effect of baseline PA on the incidence of POD in older patients undergoing elective orthopedic surgery and to determine whether these effects were independent of cognitive reserve. We hypothesize that PA protects against POD by bolstering physiologic reserve needed to withstand the stressors of surgery. DESIGN Secondary analysis of a prospective, single‐center, cohort study. SETTING Urban academic hospital. PARTICIPANTS A total of 132 nondemented, English‐speaking adults older than 60 years undergoing elective orthopedic surgery. MEASUREMENTS Subjects were screened for POD and delirium severity using the Confusion Assessment Method and the Memorial Delirium Assessment Scale. Baseline cognitive activities and PAs were assessed with a validated Leisure Activity Scale. Regular PA was categorized as 6 to 7 days per week. The association of regular PA with incidence of POD was assessed using multivariable logistic regression, adjusting for age, sex, Charlson Comorbidity Index, cognitive reserve, and cognitive function. Linear regression was used to assess the association of delirium severity with regular PA. RESULTS Of 132 patients, 41 (31.1%) developed POD. Regular PA was associated with a 74% lower odds of developing POD (odds ratio [OR] = 0.26; 95% confidence interval [CI] = 0.08‐0.82). There was no significant interaction between PA and cognitive reserve (P = .70). Of 85 women, 25 (29.4%), and of 47 men, 16 (34.0%) developed POD. In stratified analysis, women who engaged in regular PA had dramatically lower odds of POD (OR = 0.08; 95% CI = 0.01‐0.63) compared with men (OR = 0.93; 95% CI = 0.18‐4.97). CONCLUSIONS Regular PA is associated with decreased incidence of POD, especially among women. Future studies should address the basis of sex differences in PA benefits on delirium. J Am Geriatr Soc 67:2260–2266, 2019

Approximately 25% of elderly patients scheduled for carotid endarterectomy (CEA) develop post-operative cognitive dysfunction (CD). We tested the hypothesis that the plasma levels of matrix metalloproteinase 9 (MMP-9) are predictive of moderate to severe CD after CEA. A total of 73 patients were prospectively enrolled in this Institutional Review Board approved study. Plasma samples were obtained at baseline and day 1 post-surgery. We measured the plasma concentrations of both MMP-9 and its inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1). We estimated the MMP-9 activity by calculating the MMP-9:TIMP-1 ratio. The cognitive performance day 1 post-surgery was quantified with z-scores, using a control group who were undergoing spinal surgery. The criteria used to define CD was performance of ≥ 1.5 standard deviations worse than the control group; approximately 19% of eligible patients developed CD. Compared to patients without CD, this group had both higher total (81.66 ± 12.25 ng/mL versus [vs.] 43.18 ± 4.44 ng/mL, p = 0.005) and activity (0.88 ± 0.24 ng/mL vs. 0.54 ± 0.06 ng/mL, p = 0.003) MMP-9 levels at baseline. All of the results were adjusted for age, diabetes and neurovascular symptoms.