Blood pressure in old age : exploring the relation with the structure, function and hemodynamics of the brain

  With increasing age the prevalence of hypertension rises. High blood pressure at midlife is associated with cognitive impairment. Nevertheless, in older persons a lower rather than a higher blood pressure is associated with incident dementia. The main purpose of the work in this thesis was to explore the role of blood pressure in relation to cerebral structure, neurocognitive functioning and hemodynamics of the brain in old age. Therefore, we sought to determine whether discontinuation of antihypertensive therapy in persons aged 75 years and over with mild cognitive deficits and using antihypertensive medication (the Discontinuation of ANtihypertensive Treatment in Elderly people [DANTE] population) would improve their cognitive and psychological functioning. The assumption was that the increase in blood pressure after the discontinuation of antihypertensives would lead to a direct increase in cerebral blood flow and, as a consequence, to an improvement in cerebral functioning. An additional objective was to investigate possible underlying mechanisms in the relation between blood pressure and neurocognitive functioning. To enable this, brain MRI was used to determine whether (lower) blood pressure was associated with (micro)structural damage, cerebral small vessel disease and blood flow in the brain, and also whether the presence of cerebral (micro)structural damage was related to neurocognitive functioning.  Alzheimer Nederland, Chipsoft B.V., Sectra Benelux, HartstichtingLUMC / Geneeskund

Combining Cardiac Monitoring with Actigraphy Aids Nocturnal Arousal Detection during Ambulatory Sleep Assessment in Insomnia

Study Objectives: The objective assessment of insomnia has remained difficult. Multisensory devices collecting heart rate (HR) and motion are regarded as the future of ambulatory sleep monitoring. Unfortunately, reports on altered average HR or heart rate variability (HRV) during sleep in insomnia are equivocal. Here, we evaluated whether the objective quantification of insomnia improves by assessing state-related changes in cardiac measures. Methods: We recorded electrocardiography, posture, and actigraphy in 33 people without sleep complaints and 158 patients with mild to severe insomnia over 4 d in their home environment. At the microscale, we investigated whether HR changed with proximity to gross (body) and small (wrist) movements at nighttime. At the macroscale, we calculated day-night differences in HR and HRV measures. For both timescales, we tested whether outcome measures were related to insomnia diagnosis and severity. Results: At the microscale, an increase in HR was often detectable already 60 s prior to as well as following a nocturnal chest, but not wrist, movement. This increase was slightly steeper in insomnia and was associated with insomnia severity, but future EEG recordings are necessary to elucidate whether these changes occur prior to or simultaneously with PSG-indicators of wakefulness. At the macroscale, we found an attenuated cardiac response to sleep in insomnia: patients consistently showed smaller day-night differences in HR and HRV. Conclusions: Incorporating state-related changes in cardiac features in the ambulatory monitoring of sleep might provide a more sensitive biomarker of insomnia than the use of cardiac activity averages or actigraphy alone

Increased cerebral (R)-[11C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate microglia activation over time following traumatic brain injury (TBI) and to relate these findings to glutamate release.</p> <p>Procedures</p> <p>Sequential dynamic <it>(R)</it>-[¹¹C]PK11195 PET scans were performed in rats 24 hours before (baseline), and one and ten days after TBI using controlled cortical impact, or a sham procedure. Extracellular fluid (ECF) glutamate concentrations were measured using cerebral microdialysis. Brains were processed for histopathology and (immuno)-histochemistry.</p> <p>Results</p> <p>Ten days after TBI, <it>(R)</it>-[¹¹C]PK11195 binding was significantly increased in TBI rats compared with both baseline values and sham controls (p < 0.05). ECF glutamate values were increased immediately after TBI (27.6 ± 14.0 μmol·L^-1) as compared with the sham procedure (6.4 ± 3.6 μmol·L^-1). Significant differences were found between TBI and sham for ED-1, OX-6, GFAP, Perl's, and Fluoro-Jade B.</p> <p>Conclusions</p> <p>Increased cerebral uptake of <it>(R)</it>-[¹¹C]PK11195 ten days after TBI points to prolonged and ongoing activation of microglia. This activation followed a significant acute posttraumatic increase in ECF glutamate levels.</p

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

&lt;p&gt;Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (&#62;70 years).&lt;/p&gt; &lt;p&gt;Design Prospective cohort study.&lt;/p&gt; &lt;p&gt;etting PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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&#60;0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors.&lt;/p&gt; Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age

Species richness influences wine ecosystem function through a dominant species

Increased species richness does not always cause increased ecosystem function. Instead, richness can influence individual species with positive or negative ecosystem effects. We investigated richness and function in fermenting wine, and found that richness indirectly affects ecosystem function by altering the ecological dominance of Saccharomyces cerevisiae. While S. cerevisiae generally dominates fermentations, it cannot dominate extremely species-rich communities, probably because antagonistic species prevent it from growing. It is also diluted from species-poor communities, allowing yeasts with lower functional impacts to dominate. We further investigated the impacts of S. cerevisiae and its competitors in high- and low-functioning wine communities, focusing on glucose consumption as an ecosystem function. S. cerevisiae is a keystone species because its presence converts low-functioning communities to communities with the same function as S. cerevisiae monocultures. Thus, even within the same ecosystem, species richness has both positive and negative effects on function