Liselotte W. Wijsman

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.

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.

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 (ΔGDS-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 (ΔGDS-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.

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.

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)

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

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.

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.

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.

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.