Background Type 2 diabetes mellitus is associated with dementia risk, however evidence is limited for possible associations of diabetes and pre-diabetes with cognitive decline. Objective To determine if diabetes in mid-life is associated with 20-year cognitive decline, and to characterize long-term cognitive decline across clinical categories of hemoglobin A1c (HbA1c). Design Prospective cohort. Setting The community-based Atherosclerosis Risk in Communities (ARIC) Study. Participants 13351 black and white adults aged 48-67 years at baseline (1990-1992). Measurements Diabetes was defined by self-report of physician diagnosis or medication use or HbA1c≥6.5%. Undiagnosed diabetes, pre-diabetes, and glucose control in persons with diagnosed diabetes were defined using clinical categories of HbA1c. Delayed Word Recall, Digit Symbol Substitution, and Word Fluency tests were used to assess cognitive performance, and were summarized using a global Z-score. Results Diabetes in midlife was associated with significantly greater cognitive decline over 20 years (adjusted global Z-score difference=-0.15, 95% CI:-0.22,-0.08), representing a 19% greater decline than those without diabetes. Cognitive decline was significantly greater among persons with pre-diabetes (HbA1c 5.7-6.4%) than those without diabetes and HbA1c<5.7%. Participants with poorly controlled diabetes (HbA1c≥7.0%) had a larger decline compared to persons whose diabetes was controlled (adjusted global Z-score difference=-0.16,p-value=0.071). Longer duration of diabetes was also associated with greater late-life cognitive decline (p-value-for-trend=<0.001). No significant differences in the rates of declines were seen in whites compared to blacks (p-value-for-interaction=0.4357). Limitations Single measurement of HbA1c at baseline, only one test to per cognitive domain, potential geographic confounding of race comparisons. Conclusions These findings suggest that diabetes prevention and glucose control in midlife may protect against late-life cognitive decline.

Background The optimal systolic blood pressure (SBP) treatment goal is in question, with the SBP intervention trial (SPRINT) suggesting benefit for 120mmHg. However, achieving SBP this low may reduce diastolic BP (DBP) to levels that could compromise myocardial perfusion. Objectives To examine the association of DBP with prevalent and progressive myocardial damage (using high-sensitivity cardiac Troponin-T, hs-cTnT). We also examined prospective associations between DBP and coronary heart disease (CHD), stroke, or death over 21 years; overall and stratified by subgroups of interest. Methods We studied 11,565 adults from the Atherosclerosis Risk in Communities (ARIC) study. We evaluated cross-sectional DBP and hs-cTnT (dichotomized at 14 ng/L) associations with logistic regression, longitudinal associations between DBP and hs-cTnT change using generalized linear models adjusted for attrition, and prospective associations between DBP and events with Cox regression. Results Mean baseline age was 57 years, 57% were female and 25% were black. Relative to persons with DBP 80–89mmHg, those with DBP 60–69mmHg and <60mmHg had higher prevalence of baseline hs-cTnT ≥14ng/L (OR 1.5 [95%CI 1.0–2.3] and 2.2 [1.2–4.1]). Participants with DBP 60–69mmHg and <60mmHg also had relatively larger increases in hs-cTnT over the initial 6 years of follow-up (β +6 [95%CI 2–10] and +9 [3–14] ng/L). DBP <60mmHg (vs. 80–89mmHg) was associated with incident CHD (HR 1.5 [1.2–1.9]) and mortality (HR 1.3 [1.1–1.6]), but not with stroke. The DBP and incident CHD association was strongest when baseline hs-cTnT ≥14ng/L (p-value-for-interaction <0·001). Associations of low DBP with prevalent hs-cTnT and incident CHD were most pronounced among those with baseline SBP ≥120mmHg. Conclusion Particularly among adults with SBP ≥120mmHg, and thus elevated pulse-pressure, low DBP was associated with subclinical myocardial damage and CHD events. When titrating treatment to SBP <140mmHg, it may be prudent to ensure DBP levels do not fall below 70mmHg, and particularly below 60mmHg.

IMPORTANCE The association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following prolonged hypertension may be associated with poor cognitive outcomes. OBJECTIVE To examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline. DESIGN, SETTING, AND PARTICIPANTS The Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities:

IMPORTANCE Hypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age.OBJECTIVE To evaluate the association between midlife (48-67 years of age) hypertension and the 20-year change in cognitive performance.

Background Hemoglobin A1c (HbA1c) is the standard measure to monitor long-term glucose control in diabetes management and is now used for diagnosis. Fructosamine and glycated albumin are markers of short-term glycemic control that may add complementary information to HbA1c. However, the performance of fructosamine and glycated albumin to identify people at risk of complications is unclear. Methods We measured glycated albumin and fructosamine in 11348 adults without diabetes and 958 adults with diagnosed diabetes who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) Study in 1990–1992 (baseline). We evaluated the associations of fructosamine and glycated albumin with retinopathy and risk of incident chronic kidney disease and incident diabetes during two decades of follow-up. We compared these associations to those for HbA1c. Findings Fructosamine and glycated albumin were strongly associated with retinopathy and these associations were very similar to that observed for HbA1c. Fructosamine and glycated albumin were also significantly associated with risk of incident chronic kidney disease and incident diabetes. Compared to persons with no diabetes and fructosamine or glycated albumin levels <75th percentile, the multivariable-adjusted hazard ratios (95%CIs) for chronic kidney disease for persons with fructosamine and glycated albumin levels >95th percentile were 1.50 (1.22, 1.85) and 1.48 (1.20, 1.83), respectively. The HRs for incident diabetes were 4.96 (4.36, 5.64) for fructosamine >95th percentile and 6.17 (5.45, 6.99) for glycated albumin >95th percentile. Associations were attenuated but persisted after adjustment for HbA1c. Prediction of incident chronic kidney disease by fructosamine (C-statistic, 0.717) and glycated albumin (C-statistic, 0.717) were nearly as strong as by HbA1c (C-statistic, 0.726) but HbA1c outperformed fructosamine and glycated albumin for prediction of incident diabetes with C-statistics of 0.760, 0.706, and 0.703, respectively. Interpretation Fructosamine and glycated albumin were strongly associated with diabetes and its microvascular complications and complemented the prognostic utility of HbA1c.