Association of diastolic blood pressure with cardiovascular events in older people varies upon cardiovascular history.

BACKGROUND: In older age, a low DBP has been associated with increased risk of cardiovascular events, especially in frail older people. We tested the hypothesis that low DBP is associated with a high risk of cardiovascular events in people with a previous history of cardiovascular disease, as a proxy of vascular impairment. METHODS: We included 5804 participants (mean age 75 years) from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) who as part of the trial were intensively monitored for an average period of 3.2 years. DBP was categorized in low (<70 mmHg), normal (70-90 mmHg) or high (>90 mmHg). Cox proportional hazards analyses were used to estimate hazard ratio with 95% confidence intervals (CI); analyses were stratified for cardiovascular history. RESULTS: Participants with low DBP had a 1.24-fold (1.04; 1.49) increased risk of cardiovascular events compared with those with normal DBP. After further adjusting for cardiovascular factors, this association attenuated to 1.05 (0.86; 1.28). A previous history of cardiovascular disease significantly modified the relation between DBP and risk of cardiovascular events (P-interaction 0.042). In participants without a history of cardiovascular disease, DBP was marginally significantly associated with an increased event risk (hazard ratio (95% CI) per 10 mmHg increase in DBP 1.08 (0.99; 1.18), P value = 0.07), whereas in participants with a history of cardiovascular disease, higher DBP was associated with a decreased risk of cardiovascular events (hazard ratio (95% CI) per 10 mmHg increase in DBP 0.92 (0.85; 0.99, P value = 0.018). These risk estimates were independent of potential confounders, including classical cardiovascular risk factors. CONCLUSION: The association of DBP with cardiovascular events in older people varies upon their previous history, showing that in participants with preexisting cardiovascular diseases, a higher DBP associates with a decreased risk of future cardiovascular events.

Evaluation of the Use of Home Blood Pressure Measurement Using Mobile Phone-Assisted Technology: The iVitality Proof-of-Principle Study.

BACKGROUND: Mobile phone-assisted technologies provide the opportunity to optimize the feasibility of long-term blood pressure (BP) monitoring at home, with the potential of large-scale data collection. OBJECTIVE: In this proof-of-principle study, we evaluated the feasibility of home BP monitoring using mobile phone-assisted technology, by investigating (1) the association between study center and home BP measurements; (2) adherence to reminders on the mobile phone to perform home BP measurements; and (3) referrals, treatment consequences and BP reduction after a raised home BP was diagnosed. METHODS: We used iVitality, a research platform that comprises a Website, a mobile phone-based app, and health sensors, to measure BP and several other health characteristics during a 6-month period. BP was measured twice at baseline at the study center. Home BP was measured on 4 days during the first week, and thereafter, at semimonthly or monthly intervals, for which participants received reminders on their mobile phone. In the monthly protocol, measurements were performed during 2 consecutive days. In the semimonthly protocol, BP was measured at 1 day. RESULTS: We included 151 participants (mean age [standard deviation] 57.3 [5.3] years). BP measured at the study center was systematically higher when compared with home BP measurements (mean difference systolic BP [standard error] 8.72 [1.08] and diastolic BP 5.81 [0.68] mm Hg, respectively). Correlation of study center and home measurements of BP was high (R=0.72 for systolic BP and 0.72 for diastolic BP, both P<.001). Adherence was better in participants measuring semimonthly (71.4%) compared with participants performing monthly measurements (64.3%, P=.008). During the study, 41 (27.2%) participants were referred to their general practitioner because of a high BP. Referred participants had a decrease in their BP during follow-up (mean difference final and initial [standard error] -5.29 [1.92] for systolic BP and -2.93 [1.08] for diastolic BP, both P<.05). CONCLUSION: Mobile phone-assisted technology is a reliable and promising method with good adherence to measure BP at home during a 6-month period. This provides a possibility for implementation in large-scale studies and can potentially contribute to BP reduction.

An Internet-Based Physical Activity Intervention to Improve Quality of Life of Inactive Older Adults: A Randomized Controlled Trial.

BACKGROUND: Increasing physical activity is a viable strategy for improving both the health and quality of life of older adults. OBJECTIVE: The aim of this study was to assess if an Internet-based intervention aimed to increase physical activity was effective in improving quality of life of inactive older adults. In addition, we analyzed the effect of the intervention on quality of life among those participants who successfully reached their individually targeted increase in daily physical activity as indicated by the intervention program, as well as the dose-response effect of increasing physical activity on quality of life. METHODS: The intervention was tested in a randomized controlled trial and was comprised of an Internet program-DirectLife (Philips)-aimed at increasing physical activity using monitoring and feedback by accelerometry and feedback by digital coaching (n=119). The control group received no intervention (n=116). Participants were inactive 60-70-year-olds and were recruited from the general population. Quality of life and physical activity were measured at baseline and after 3 months using the Research ANd Development 36-item health survey (RAND-36) and wrist-worn triaxial accelerometer, respectively. RESULTS: After 3 months, a significant improvement in quality of life was seen in the intervention group compared to the control group for RAND-36 subscales on emotional and mental health (2.52 vs -0.72, respectively; P=.03) and health change (8.99 vs 2.03, respectively; P=.01). A total of 50 of the 119 participants (42.0%) in the intervention group successfully reached their physical activity target and showed a significant improvement in quality of life compared to the control group for subscales on emotional and mental health (4.31 vs -0.72, respectively; P=.009) and health change (11.06 vs 2.03, respectively; P=.004). The dose-response analysis showed that there was a significant association between increase in minutes spent in moderate-to-vigorous physical activity (MVPA) and increase in quality of life. CONCLUSIONS: Our study shows that an Internet-based physical activity program was effective in improving quality of life in 60-70-year-olds after 3 months, particularly in participants that reached their individually targeted increase in daily physical activity. TRIAL REGISTRATION: Nederlands Trial Register: NTR 3045; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3045 (Archived by WebCite at http://www.webcitation.org/6fobg2sjJ).

High-sensitivity cardiac troponin T is associated with cognitive decline in older adults at high cardiovascular risk.

AIMS: Cardiac troponin T (cTnT), measured with a high-sensitivity (hs) assay, is associated with cognitive decline, but the underlying mechanism is unknown. We investigated the association of hs-cTnT with cognitive function and decline, and studied whether this association was independent of cardiovascular diseases or risk factors, and N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: We studied 5407 participants (mean age 75.31 years) from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), who all had cardiovascular diseases or risk factors thereof. Participants with pre-existent advanced clinical heart failure were excluded. Hs-cTnT and NT-proBNP obtained after 6 months of follow-up were related with cognitive function, tested repeatedly during a mean follow-up of 3.2 years. Participants with higher hs-cTnT performed worse at baseline on Stroop test (mean baseline score (standard error (SE)) lowest vs highest third 65.91 (1.16) vs 69.40 (1.10) seconds, p < 0.001), Letter-Digit Coding test (23.35 (0.32) vs 22.40 (0.31) digits coded, p < 0.001), immediate Picture-Word Learning test (9.45 (0.09) vs 9.31 (0.08) pictures remembered, p = 0.002) and delayed Picture-Word Learning test (10.33 (0.12) vs 10.10 (0.12) pictures remembered, p = 0.013). Furthermore, participants with higher hs-cTnT had steeper decline on Stroop test (mean annual change (SE) lowest vs highest third 0.34 (0.12) vs 1.06 (0.12) seconds, p = 0.013), Letter-Digit Coding test (-0.29 (0.03) vs -0.46 (0.03) digits coded, p < 0.001), immediate Picture-Word Learning test (0.01 (0.01) vs -0.06 (0.01) pictures remembered, p < 0.001) and delayed Picture-Word Learning test (-0.03 (0.01) vs -0.12 (0.02) pictures remembered, p = 0.001). Associations were independent of cardiovascular diseases risk factors or Apolipoprotein E genotype. Further adjusting for NT-proBNP levels revealed the same results. CONCLUSIONS: Higher levels of hs-cTnT associate with worse cognitive function and steeper cognitive decline in older adults independent of cardiovascular diseases, risk factors and NT-proBNP.

Risk stratification and treatment effect of statins in secondary cardiovascular prevention in old age: Additive value of N-terminal pro-B-type natriuretic peptide.

BACKGROUND: To date, no validated risk scores exist for prediction of recurrence risk or potential treatment effect for older people with a history of a cardiovascular event. Therefore, we assessed predictive values for recurrent cardiovascular disease of models with age and sex, traditional cardiovascular risk markers, and 'SMART risk score', all with and without addition of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Treatment effect of pravastatin was assessed across low and high risk groups identified by the best performing models. DESIGN AND METHODS: Post-hoc analysis in 2348 participants (age 70-82 years) with a history of cardiovascular disease within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. Composite endpoint was a recurrent cardiovascular event/cardiovascular mortality. RESULTS: The models with age and sex, traditional risk markers and SMART risk score had comparable predictive values (area under the curve (AUC) 0.58, 0.61 and 0.59, respectively). Addition of NT-proBNP to these models improved AUCs with 0.07 (p for difference ((pdiff)) = 0.003), 0.05 (pdiff = 0.009) and 0.06 (pdiff < 0.001), respectively. For the model with age, sex and NT-proBNP, the hazard ratio for the composite endpoint in pravastatin users compared with placebo was 0.67 (95% confidence interval 0.49-0.90) for those in the highest third of predicted risk and 0.91 (0.57-1.46) in the lowest third, number needed to treat 12 and 115 (pdiff = 0.038) respectively. CONCLUSION: In secondary cardiovascular prevention in old age addition of NT-proBNP improves prediction of recurrent cardiovascular disease, cardiovascular mortality and treatment effect of pravastatin. A minimal model including age, sex and NT-proBNP predicts as accurately as complex risk models including NT-proBNP.

Subclinical Thyroid Dysfunction and Depressive Symptoms among the Elderly: A Prospective Cohort Study.

BACKGROUND: Subclinical hypothyroidism has been associated with depressive symptoms in cross-sectional studies, but prospective data and data on subclinical hyperthyroidism are scarce. METHODS: In the Leiden substudy of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), thyroid-stimulating hormone and free T4 levels were measured at baseline and repeated after 6 months in adults aged 70-82 years with preexisting cardiovascular disease or known cardiovascular risk factors to define persistent thyroid functional status. Main outcome measures were depressive symptoms, assessed with the Geriatric Depression Scale 15 (GDS-15) at baseline and after 3 years. All analyses were adjusted for age, gender and education. RESULTS: In 606 participants (41% women; mean age 75 years) without antidepressant medication, GDS-15 scores at baseline did not differ for participants with subclinical hypothyroidism (n = 47; GDS-15 score 1.75, 95% CI 1.29-2.20, p = 0.53) or subclinical hyperthyroidism (n = 13; GDS-15 score 1.64, 95% CI 0.78-2.51, p = 0.96) compared to euthyroid participants (n = 546; mean GDS-15 score 1.60, 95% CI 1.46-1.73). After 3 years, compared to the euthyroid participants, changes in GDS-15 scores did not differ for participants with subclinical hypothyroidism (x0394;GDS-15 score -0.03, 95% CI -0.50 to 0.44, p = 0.83), while subclinical hyperthyroidism was associated with an increase in GDS scores (x0394;GDS-15 score 1.13, 95% CI 0.32-1.93, p = 0.04). All results were similar for persistent subclinical thyroid dysfunction. CONCLUSIONS: In this largest prospective study on the association of persistent subclinical thyroid dysfunction and depression, subclinical hypothyroidism was not associated with increased depressive symptoms among older adults at high cardiovascular risk. Persistent subclinical hyperthyroidism might be associated with increased depressive symptoms, which requires confirmation in a larger prospective study.

Blood Pressure Lowering Medication, Visit-to-Visit Blood Pressure Variability, and Cognitive Function in Old Age.

BACKGROUND: Visit-to-visit blood pressure (BP) variability is associated with cognitive impairment. We assessed to what extent the association between BP variability and cognitive impairment is mediated by the association of BP lowering medication (BPLM) with both BP variability and cognition. METHODS: We studied 5,606 participants from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). BP was measured every 3 months during 3.2 years; BP variability was defined as the SD of BP measurements during follow-up. Cognitive function was assessed at baseline and during follow-up using the Stroop test, Letter-Digit Coding test, and immediate and delayed Picture-Word Learning tests. Multivariate regression models were used with and without adjustments for BPLM to calculate the percentage to which BPLM mediated the association between BP variability and cognition. RESULTS: Participants taking calcium antagonists had a higher score in baseline Letter-Digit Coding test (mean difference (95% confidence interval (CI) 0.45 (0.06; 0.88). Participants taking beta-blockers had a steeper decline in Stroop test (additional change per year (95% CI) 0.40 (0.09; 0.70) and Letter-Digit Coding test (0.08 (-0.15; -0.02)). Furthermore, a steeper decline in Stroop test was found in participants taking renin-angiotensin system (RAS) inhibitors (0.50 (0.16; 0.85). Systolic BP variability was higher in participants taking beta-blockers and RAS inhibitors (mean difference in systolic BP variability in mm Hg (95% CI) 0.75 (0.45; 1.04) and 1.37 (1.04; 1.71) respectively). Participants taking diuretics, calcium antagonists, and RAS inhibitors had a higher diastolic BP variability (mean difference in diastolic BP variability in mm Hg (95% CI) 0.27 (0.04; 0.49), 0.37 (0.12; 0.62) and 0.65 (0.37; 0.93) SD, respectively). Beta estimates remained essentially the same when we adjusted for BPLM in the association of BP variability with cognitive function. CONCLUSIONS: The association between BP variability and cognitive impairment was not mediated by BPLM.

User preferences and usability of iVitality: optimizing an innovative online research platform for home-based health monitoring.

BACKGROUND: The iVitality online research platform has been developed to gain insight into the relationship between early risk factors (ie, poorly controlled hypertension, physical or mental inactivity) and onset and possibly prevention of dementia. iVitality consists of a website, a smartphone application, and sensors that can monitor these indicators at home. Before iVitality can be implemented, it should fit the needs and preferences of users, ie, offspring of patients with dementia. This study aimed to explore users' motivation to participate in home-based health monitoring research, to formulate requirements based on users' preferences to optimize iVitality, and to test usability of the smartphone application of iVitality. METHODS: We recruited 13 participants (aged 42-64 years, 85% female), who were offspring of patients with dementia. A user-centered methodology consisting of four iterative phases was used. Three semistructured interviews provided insight into motivation and acceptance of using iVitality (phase 1). A focus group with six participants elaborated on expectations and preferences regarding iVitality (phase 2). Findings from phase 1 and 2 were triangulated by two semistructured interviews (phase 3). Four participants assessed the usability of the smartphone application (phase 4) using a think aloud procedure and a questionnaire measuring ease and efficiency of use (scale 1-7; higher scores indicated better usability). RESULTS: All participants were highly motivated to contribute to dementia research. However, the frequency of home-based health monitoring should not be too high. Participants preferred to receive feedback about their measurements and information regarding the relationship between these measurements and dementia. Despite minor technical errors, iVitality was considered easy and efficient to use (mean score 5.50, standard deviation 1.71). CONCLUSION: Offspring of patients with dementia are motivated to contribute to home-based monitoring research by using iVitality and are able to use the smartphone application. The formulated requirements will be embedded to optimize iVitality.

Biological correlates of blood pressure variability in elderly at high risk of cardiovascular disease.

BACKGROUND: Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular disease. This study investigates biological correlates of intra-individual variability in blood pressure in older persons. METHODS: Nested observational study within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) among 3,794 male and female participants (range 70-82 years) with a history of, or risk factors for cardiovascular disease. Individual visit-to-visit variability in systolic and diastolic blood pressure and pulse pressure (expressed as 1 SD in mm Hg) was assessed using nine measurements over 2 years. Correlates of higher visit-to-visit variability were examined at baseline, including markers of inflammation, endothelial function, renal function and glucose homeostasis. RESULTS: Over the first 2 years, the mean intra-individual variability (1 SD) was 14.4mm Hg for systolic blood pressure, 7.7mm Hg for diastolic blood pressure, and 12.6mm Hg for pulse pressure. After multivariate adjustment a higher level of interleukin-6 at baseline was consistently associated with higher intra-individual variability of blood pressure, including systolic, diastolic, and pulse pressure. Markers of endothelial function (Von Willebrand factor, tissue plasminogen activator), renal function (glomerular filtration rate) and glucose homeostasis (blood glucose, homeostatic model assessment index) were not or to a minor extent associated with blood pressure variability. CONCLUSION: In an elderly population at risk of cardiovascular disease, inflammation (as evidenced by higher levels of interleukin-6) is associated with higher intra-individual variability in systolic, diastolic, and pulse pressure.

NT-proBNP, blood pressure, and cognitive decline in the oldest old: The Leiden 85-plus Study.

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 = 0.004), and had a 0.24-point-steeper decline in MMSE score per year (p = 0.021). The longitudinal association disappeared after full adjustment for possible confounders (0.14-point-steeper decline, p = 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.

N-terminal pro-brain natriuretic peptide and cognitive decline in older adults at high cardiovascular risk.

OBJECTIVE: Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cognitive impairment, which might be explained by cardiovascular diseases or risk factors. The aim of this study was to investigate the association of NT-proBNP with cognitive function and decline in older adults at high risk of cardiovascular disease. METHODS: We studied 5,205 men and women (mean age = 75 years) who were recruited into the PROspective Study of Pravastatin in the Elderly at Risk. All participants had pre-existing cardiovascular disease or risk factors thereof. Four domains of cognitive function were tested at baseline and repeated during a follow-up period of 3.2 years. RESULTS: Participants with higher NT-proBNP (≥450ng/l) had worse baseline cognitive function, including reaction time (mean difference high vs low group = 3.07 seconds, 95% confidence interval [CI] = 0.83 to 5.32), processing speed (-1.02 digits coded, 95% CI = -1.65 to -0.39), and immediate memory (-0.13 pictures remembered, 95% CI = -0.29 to 0.04). There was no significant difference in delayed memory (-0.14, 95% CI = -0.38 to 0.10) between the NT-proBNP groups. Participants with higher NT-proBNP had a steeper cognitive decline, including reaction time (mean annual change high vs low group = 0.60 seconds, 95% CI = 0.14 to 1.07), processing speed (-0.15 digits coded, 95% CI = -0.25 to -0.05), immediate memory (-0.05 pictures remembered, 95% CI = -0.09 to 0.00), and delayed memory (-0.05 pictures remembered, 95% CI = -0.11 to 0.01). Associations were independent of cardiovascular diseases and risks. INTERPRETATION: Higher NT-proBNP associates with worse cognitive function and steeper cognitive decline, independent of cardiovascular diseases and risks. Further studies to unravel the underlying mechanisms are warranted.

Subclinical thyroid dysfunction and functional capacity among elderly.

BACKGROUND: Subclinical thyroid dysfunction is common among older people and has been associated with decreased functional capacity but with conflicting data. The aim of this study was to assess the association between subclinical thyroid dysfunction and functional capacity in an elderly population. METHODS: We included 5182 participants with a mean age of 75.2 years from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Self-reported functional capacity was assessed using the Barthel Index (BI) and the Instrumental Activities of Daily Living (IADL) scores at baseline and during follow-up. Participants with subclinical hyperthyroidism (n=65) and subclinical hypothyroidism (n=173) were compared to euthyroid participants (n=4944). The association between persistent subclinical thyroid dysfunction and functional capacity and decline was also investigated. RESULTS: At baseline, compared to euthyroid participants (BI 19.73±SE 0.06; IADL 13.52±0.02), there was no difference in functional capacity for participants with subclinical hyperthyroidism (BI 19.60±0.09; IADL 13.51±0.12, p>0.05) or subclinical hypothyroidism (BI 19.82±0.06; IADL 13.55±0.08, p>0.05). Over a mean 3.2-year follow-up period, there was no association between thyroid function and annual decline of either BI or IADL (p>0.05). No association was found between persistent subclinical thyroid dysfunction and functional capacity at baseline or during follow-up (p>0.05). Results were similar after excluding participants with a maximum BI and/or IADL score at baseline. CONCLUSION: Among well-functioning community-dwelling elderly, we found no evidence that subclinical thyroid dysfunction contributes to decreased functional capacity.

Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study.

OBJECTIVE: To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (>70 years). DESIGN: Prospective cohort study. SETTING: PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands. PARTICIPANTS: 5461 participants, mean age 75.3 years, who were at risk of cardiovascular disease. Blood pressure was measured every three months during an average of 3.2 years. Visit-to-visit variability in blood pressure was defined as the standard deviation of blood pressure measurements between visits. MAIN OUTCOME MEASURES: Four domains of cognitive function, testing selective attention, processing speed, and immediate and delayed memory. In a magnetic resonance imaging substudy of 553 participants, structural brain volumes, cerebral microbleeds, infarcts, and white matter hyperintensities were measured. RESULTS: Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests: attention (mean difference high versus low thirds) 3.08 seconds (95% confidence interval 0.85 to 5.31), processing speed -1.16 digits coded (95% confidence interval -1.69 to -0.63), immediate memory -0.27 pictures remembered (95% confidence interval -0.41 to -0.13), and delayed memory -0.30 pictures remembered (95% confidence interval -0.49 to -0.11). Furthermore, higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infarcts, and higher variability in diastolic blood pressure was associated with cerebral microbleeds (all P<0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors. CONCLUSION: Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age.

Subclinical thyroid dysfunction and cognitive decline in old age.

BACKGROUND: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS: Prospective longitudinal study of men and women aged 70-82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests. RESULTS: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up. CONCLUSION: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.