Cardiovascular and hemodynamic contribution to brain aging

In summary, chapter 1 of this thesis provides a background on the demographic, biologic and cardiovascular aspects of brain aging. Chapter 2 shows that higher blood pressure is associated with lower cognitive decline in very old age. Findings of Chapter 3 indicate that higher blood pressure is associated with lower risk of stroke in very old subjects with higher degrees of disability. In chapter 4, we showed that visit-to-visit blood pressure variability might put subjects at a higher risk for accelerated brain aging. In Chapters 5 to 7, we observed that a strong association exists between a graded decrease in cardiac function and lower brain volumes and cognitive performance. In a meta-analysis (Chapter 8), we demonstrated that in patients with Alzheimer__s disease and vascular dementia have profound disturbances in their cerebrovascular hemodynamics. Chapter 9 shows that in late life, conventional cardiovascular risk factors loss their predictive value while impaired cognitive function better predicts risk of stroke. In Chapter 10, we showed that increased serum markers of endothelial dysfunction associate with lower cerebral blood flow in older subjects. In Chapter 11, we demonstrated that older subjects with lower cerebral blood flow have a shorter survival. Chapter 12 reviews the key findings of this thesis and discusses them in the context of current knowledge and evidence.Financial support for printing of this thesis was provided by the Leiden University Medical Centre, Leyden Academy on Vitality and Ageing, and Internationale Stichting Alzheimer Onderzoek (ISAO.UBL - phd migration 201

Cognitive impairment and risk of stroke in the oldest old: the Leiden 85-plus study

Public Health and primary careGeriatrics in primary car

Contributions of cerebral blood flow to associations between blood pressure levels and cognition the age, gene/environment susceptibility-Reykjavik study

Cerebral hypoperfusion leads to adverse sequalae including dementia. Midlife higher blood pressure (BP) can lead to low cerebral blood flow (CBF), but older persons may need higher BP to maintain cerebral perfusion. We investigated the associations among late-life BP, CBF, and cognition. Data are from 2498 participants with a mean age of 79.8 (SD, 4.7) years of the second exam of the AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study. BP was measured, and phase-contrast (PC) magnetic resonance imaging was acquired to estimate total brain CBFPC. Cognitive outcomes included verbal and working memory, processing speed, mild cognitive impairment, and all-cause dementia. Relationships among late-life BP, CBFPC, and cognition were assessed with regression models, controlling for socio-demographics, BP level at midlife (at a mean age of 49.6 [SD, 5.9] years), cardiovascular factors, and total brain volume. In fully adjusted models, each mm Hg increase in late-life diastolic BP was associated with a -0.082 mL/min per 100 mL (95% CI -0.123 to -0.041) lower CBFPC. In contrast, each mm Hg increase in late-life systolic BP or pulse pressure was associated with a 0.027 mL/min per 100 mL (95% CI, 0.0065-0.048) and 0.061 mL/min per 100 mL (95% CI, 0.038-0.084) higher late-life CBFPC, respectively. Higher CBFPC was significantly related to higher cognitive scores for psychomotor speed, verbal, and working memory and to a lower odd of mild cognitive impairment or dementia, irrespective of late-life BP level. Higher late-life diastolic BP and systolic BP were differentially associated with CBFPC. Our findings suggest CBF is an important correlate of late-life cognition, independent of BP level.Neuro Imaging Researc

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

<p>Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (>70 years).</p> <p>Design Prospective cohort study.</p> <p>etting PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands.</p> <p>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.</p> <p>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.</p> <p>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.</p> Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age

Interplay of circulating leptin and obesity in cognition and cerebral volumes in older adults

We aimed to investigate whether circulating leptin and body mass index (BMI) associate independently with cognitive function (decline) and brain volumes using magnetic resonance imaging (MRI) in older individuals at risk of cardiovascular disease. We studied the cross-sectional and longitudinal associations in participants enrolled in the PROSPER study (Prospective Study of Pravastatin in the Elderly at Risk). Cognitive function was tested at baseline and repeated during a mean follow-up time of 3.2 years. Analyses were performed with multivariable (repeated) linear regression models and adjusted for demographics, cardiovascular risk-factors, and stratified by sex. We included 5623 dementia-free participants (52 % female, mean age 75 years) with a mean BMI of 26.9 (SD = 4.1). In a sub-study, 527 participants underwent brain MRI. At baseline, individuals with a BMI > 30 had a worse performance on the Stroop test (beta 5.0 s, 95 %CI 2.6;7.5) and larger volumes of the amygdala (beta 234 mm(3), 95 %CI 3;464) and hippocampus (beta 590 mm(3), 95 %CI 181;999), independent of intracranial volume and serum leptin levels, compared with individuals with the reference BMI (BMI 18-25 kg/m(2)). Per log ng/mL higher serum leptin, independent of BMI, a 135 mm(3) (95 %CI 2;268) higher volume of the amygdala was found, but no association was observed with cognitive tests nor with other brain volumes. Stratification for sex did not materially change the results. Whereas higher BMI associated with worse cognitive function independent of leptin levels, our study provided evidence that leptin and BMI independently associate with amygdala volume suggesting potential distinct biological associations.Neuro Imaging Researc

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

Neuro Imaging Researc

Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer's Disease Patients

Pathophysiology, epidemiology and therapy of agein

Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer's Disease Patients

Pathophysiology, epidemiology and therapy of agein

Migraine and restless legs syndrome: is there an association?

Occasional clinical reports have suggested a link between migraine and restless legs syndrome. We undertook a systematic review of the evidence, which supports this association, and consider possible shared pathogenic mechanisms and the implications for current clinical practice