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IMPORTANCE It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. OBJECTIVE To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. DESIGN, SETTING, AND PARTICIPANTS Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. EXPOSURES Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). MAIN OUTCOMES AND MEASURES Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). RESULTS Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, −2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, −0.1 [95% CI, −4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). CONCLUSIONS AND RELEVANCE In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older.

In very old age, both decreasing trend in SBP over the previous 5 years and the current SBP value independently contribute to prediction of all-cause mortality. Therefore, in individual patients, all available preceding SBP measurements should be taken into account.

Objective: To study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used as a marker of heart failure in clinical practice, blood pressure (BP), and cognitive decline in the oldest old.Methods: In 560 participants of the Leiden 85-plus Study, we measured NT-proBNP levels and BP at age 85 years, at baseline, and global cognitive function (Mini-Mental State Examination [MMSE]) annually during the follow-up of 5 years.Results: Subjects in the highest tertile of NT-proBNP levels scored 1.7 points lower on the MMSE at age 85 years than subjects in the lowest tertile (p 5 0.004), and had a 0.24-point-steeper decline in MMSE score per year (p 5 0.021). The longitudinal association disappeared after full adjustment for possible confounders (0.14-point-steeper decline, p 5 0.187). Subjects in the category "highest tertile of NT-proBNP and the lowest tertile of systolic BP" had a 3.7-point-lower MMSE score at baseline (p , 0.001) and a 0.49-point-steeper decline in MMSE score per year (p , 0.001) compared with subjects in the other categories. Conclusions:In the oldest old, high NT-proBNP levels are associated with lower MMSE scores. The combination of high NT-proBNP levels and low systolic BP is associated with worst global cognitive function and the steepest cognitive decline. Possibly, a failing pump function of the heart results in lower BP and lower brain perfusion with resultant brain dysfunction. Cardiovascular diseases, such as myocardial infarction, generalized atherosclerosis, and stroke have been associated with increased dementia risk and cognitive decline.1-4 Hypertension, however, is only a risk factor for dementia when present in middle age, whereas most studies show that dementia and cognitive decline in the oldest old associate with lower blood pressures. 5In the oldest old, blood pressures decrease over time, 6,7 and stronger declines are related to the presence of dementia and cognitive decline. 8,9 One possible explanation for the blood pressure decline in the oldest old might be the increasing prevalence of (subclinical) congestive heart failure.10 Despite this dynamic correlation between blood pressure and cardiac function in relation to cognitive function in old age, previous studies have mainly focused on either the association of blood pressure or cardiac function with cognitive impairment.Congestive heart failure has been associated with an increased risk of cognitive impairment. 11-13A frequently used serum marker of heart failure is the N-terminal pro-brain natriuretic peptide (NT-proBNP), the inactive fragment of the proBNP hormone. 14 NT-proBNP has proven to be a quantitative marker of acute heart failure in clinical practice, with high sensitivity and reasonable specificity, 15 although elevated NT-proBNP levels are not specific for heart failure in the general population. Several studies have shown that higher NT-proBNP levels associate with lower cognitive function. 16,17 However, the relation among NT-proBNP levels, blood pressure, and cognitive f...