Cortisol and cognition in type 2 diabetes RESULTS Subject characteristics and potential confounding factors Characteristics of the study population are shown in Table 1. Characteristics of the 919 subjects who were recruited into the ET2DS were similar to those of non- responders in terms of age, multiple de- privation category, duration of diabetes, A1C levels, the proportion using insulin, total cholesterol, and systolic blood pres- sure (data not shown). Table 2 shows the correlations between cortisol and cogni- tive and metabolic variables. Cortisol lev- els were similar in men and women. Cortisol levels increased slightly with age but did not differ according to smoking or alcohol consumption, marital status, or education. All tests of cognitive function were poorer with increasing age and those with higher HADS depression scores. Cortisol and cognitive ability In univariate analyses, cortisol was not as- sociated with current general cognitive ability (g) or with individual tests of cog- nitive function (Table 3). Trends for an association of higher cortisol levels with poorer working memory and processing speed (assessed by LNS and DST) were absent after adjustment for age and sex (Table 3, model 1). Cortisol was not asso- ciated with peak prior cognitive ability measured by MHVS. After adjustment for MHVS to esti- mate cognitive change from an individu- al’s estimated prior function and age and sex, higher cortisol levels were associated with poorer working memory (LNS) and processing speed (DST) (P 0.05) (Table 3, model 2). These associations persisted (P 0.05) after inclusion of other poten- tial confounding factors in the model (Ta- ble 3, model 3). Finally, we tested for interaction terms between cortisol and all the vari- ables included in the regression analysis (Table 3, model 4). There were no signiﬁ- cant interaction terms for any of the cog- nitive domains other than for LNS and g. In the regression analysis for LNS, two interaction terms entered the equation, namely cortisol by ABI and cortisol by al- cohol. Inclusion of these interaction terms modestly altered , but the model remained signiﬁcant. In the regression analysis for g, there was also an interac- tion between cortisol and ABI. Inclusion of this interaction term resulted in the ﬁ- nal model achieving statistical signiﬁ- cance. Results of this model are illustrated Table 1—Characteristics of study participants in ET2DS All subjects n 919 Sociodemographic and lifestyle variables Age at assessment (years) 67.9 (4.2) Marital status Married 649 (70.8) Living with long-term partner 49 (5.3) Single 131 (14.3) Widowed 88 (9.6) Education University/college 148 (16.1) Other professional qualiﬁcation 265 (28.8) Secondary school 500 (54.4) Primary school 6 (0.7) Current smoking 120 (13.1) Alcohol consumption (frequency) Never 187 (20.5) One to four times/month 402 (44.0) Two to ﬁve times/week 229 (25.1) Six or more times/week 96 (10.5) Cognitive assessment Mini-Mental State Examination 28.3 (1.9) MHVS 31.0 (5.2) Faces and family pictures subtest 65.9 (7.9) Logical memory 25.2 (8.2) LNS 9.7 (2.7) Matrix reasoning 13.0 (5.3) DST 49.5 (14.9) Verbal ﬂuency test 36.9 (12.8) lnTMT 4.68 (0.4) General cognitive ability factor (g) 0.01 (0.99) Anxiety and depressive symptoms HADS anxiety score 5.6 (3.9) HADS depression score 3.8 2.8 Plasma cortisol levels (nmol/l) 733 (192) Diabetes and metabolic variables Duration of diabetes (years) 9.1 (6.5) Systolic blood pressure (mmHg) 133.2 (16.3) Diastolic blood pressure (mmHg) 69.1 (9.1) Total cholesterol (mmol/l) 4.3 (0.9) A1C (%) 7.4 (1.1) BMI (kg/m2) 31.3 (5.6) Ischemic heart disease (angina or myocardial infarction) 278 (30.3) Myocardial infarction 126 (13.7) Angina 252 (27.4) ABI* 0.98 (0.21) Cerebrovascular disease (transient ischemic attack or stroke) 81 (8.8) Treatments Treatment of diabetes Diet alone 171 (18.6) Hypoglycemic oral agents 590 (64.2) Insulin with or without hypoglycemic oral agents 158 (17.2) Lipid-lowering drugs 777 (84.5) Antihypertensive treatment 725 (78.9) Antidepressant(s) 108 (11.8) Data are means SD or n (%). *ABI, lowest ankle systolic pressure divided by higher of two brachial systolic pressures, a measure of subclinical atherosclerosis. 716 DIABETES CARE, VOLUME 33, NUMBER 4, APRIL 2010 care.diabetesjournals.org