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 Approximately 1 million patients in the United States with type 2 diabetes mellitus and mild-to-moderate kidney disease do not receive guideline-directed therapy with metformin. This may reflect uncertainty regarding the risk of acidosis in patients with chronic kidney disease. OBJECTIVE To quantify the association between metformin use and hospitalization with acidosis across the range of estimated glomerular filtration rate (eGFR), accounting for change in eGFR stage over time. DESIGN, SETTING, AND PARTICIPANTS Community-based cohort of 75 413 patients with diabetes in Geisinger Health System, with time-dependent assessment of eGFR stage from January 2004 until January 2017. Results were replicated in 67 578 new metformin users and 14 439 new sulfonylurea users from 2010 to 2015, sourced from 350 private US health systems. EXPOSURES Metformin use. MAIN OUTCOMES AND MEASURES Hospitalization with acidosis (International Classification of Diseases, Ninth Revision, Clinical Modification code of 276.2). RESULTS In the primary cohort (n = 75 413), mean (SD) patient age was 60.4 (15.5) years, and 51% (n = 38 480) of the participants were female. There were 2335 hospitalizations with acidosis over a median follow-up of 5.7 years (interquartile range, 2.5-9.9 years). Compared with alternative diabetes management, time-dependent metformin use was not associated with incident acidosis overall (adjusted hazard ratio [HR], 0.98; 95% CI, 0.89-1.08) or in patients with eGFR 45 to 59 mL/min/1.73 m 2 (adjusted HR, 1.16; 95% CI, 0.95-1.41) and eGFR 30 to 44 mL/min/1.73 m 2 (adjusted HR, 1.09; 95% CI, 0.83-1.44). On the other hand, metformin use was associated with an increased risk of acidosis at eGFR less than 30 mL/min/1.73 m 2 (adjusted HR, 2.07; 95% CI, 1.33-3.22). Results were consistent when new metformin users were compared with new sulfonylurea users (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 0.77; 95% CI, 0.29-2.05), in a propensity-matched cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 0.71; 95% CI, 0.45-1.12), when baseline insulin users were excluded (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 1.16; 95% CI, 0.87-1.57), and in the replication cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 0.86; 95% CI, 0.37-2.01). CONCLUSIONS AND RELEVANCE In 2 real-world clinical settings, metformin use was associated with acidosis only at eGFR less than 30 mL/min/1.73 m 2. Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m 2 .

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Key Points Question To what extent are magnetic resonance imaging–measurable brain lesions associated with dementia and mild cognitive impairment (MCI) among older people? Findings In this cohort study of 1553 participants, lower volumes in the Alzheimer disease signature region (hippocampus, entorhinal cortex, and surrounding structures), lobar microhemorrhages, and higher white matter hyperintensity volumes were independent risk factors for dementia and MCI. Findings suggested vascular changes were more important in the development of MCI than in its progression to dementia, whereas Alzheimer disease–related signs were important in both stages. Meaning Alzheimer disease–related and vascular-specific magnetic resonance imaging signs together may be associated with the further risk of dementia and MCI in an older population.

BackgroundEvidence regarding the association of lower extremity peripheral arterial disease with quality of life (QOL) is mainly from selected clinical populations or relatively small clinical cohorts. Thus, we investigated this association in community‐derived populations.Methods and ResultsUsing data of 5115 participants aged 66 to 90 years from visit 5 (2011‐2013) of the Atherosclerosis Risk in Communities Study, we quantified the associations of ankle‐brachial index (ABI) with several QOL parameters, including 12‐item Short‐Form Health Survey (SF‐12), after accounting for potential confounders using linear and logistic regression models. Peripheral arterial disease defined by an ABI <0.90 (n=402), was independently associated with a low SF‐12 Physical Component Summary score (−3.26 [95% CI −5.60 to −0.92]), compared to the ABI reference 1.10 to 1.19 (n=1900) but not with the Mental Component Summary score (−0.07 [−2.21 to 2.06]). A low ABI was significantly associated with poorer status of all SF‐12 physical domains (physical functioning, role‐physical, bodily pain, and general health) but only vitality out of 4 mental domains. Similarly, low ABI values were more consistently associated with other physically related QOL parameters (leisure‐time exercise/activity/walking) than mentally related parameters (significant depressive symptoms and hopeless feeling). Lower physical QOL was observed even in individuals with borderline low ABI (0.90 to 0.99; n=426).ConclusionsLow ABI (even borderline) was independently associated with poor QOL, especially for physical components, in community‐dwelling older adults. QOL is a critical element for older adults, and thus, further studies are warranted to assess whether peripheral arterial disease‐specific management can improve QOL in older populations.

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Background Arterial stiffness independently predicts cardiovascular disease. However, few studies have evaluated the associations of central and peripheral pulse wave velocity (PWV) with biomarkers of both myocardial stress (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin-T [hs-cTnT]) among persons without cardiac disease. Methods We examined 3,348 participants (67–90 years) without prevalent cardiac disease in the Atherosclerosis Risk in Communities (ARIC) Study (2011–13). The cross-sectional associations of PWV quartiles for central arterial segments (carotid-femoral, heart-carotid, heart-femoral) and peripheral artery (femoral-ankle) with NT-proBNP and hs-cTnT were evaluated accounting for potential confounders. Results Most PWV measures demonstrated J- or U-shaped associations with the two cardiac biomarkers. The highest (Q4) vs. second lowest (Q2) quartile of central PWV measures (carotid-femoral, heart-carotid, heart-femoral PWV) were associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were less evident for hs-cTnT. These associations were attenuated after adjusting for traditional cardiovascular risk factors, but the heart-carotid PWV-NT-proBNP relationship remained borderline significant (difference in log-NT-proBNP = 0.08 [-0.01, 0.17] in Q4 vs. Q2, p = 0.07). Peripheral PWV demonstrated inverse associations. Higher values of NT-proBNP were seen in the lowest vs. second lowest quartile of all PWV measures. Conclusions Central stiffness measures showed stronger associations with cardiac biomarkers (particularly NT-proBNP) than peripheral measures among older adults without cardiac disease. Our findings are consistent with the concept of ventricular-vascular coupling and suggest that central rather than peripheral arterial hemodynamics are more closely related to myocardial stress rather than damage.