R.W.M.M. Jansen

Cerebral Autoregulation: An Overview of Current Concepts and Methodology with Special Focus on the Elderly

Cerebral autoregulation (CA) refers to the properties of the brain vascular bed to maintain cerebral perfusion despite changes in blood pressure (BP). Whereas classic studies have assessed CA during changes in BP that have a gradual onset, dynamic studies quantify the fast modifications in cerebral blood flow (CBF) in relation to rapid alterations in BP. There is a lack of standardization in the assessment of dynamic CA. This review provides an overview of the methods that have been applied, with special focus on the elderly. We will discuss the relative merits and shortcomings of these methods with regard to the aged population. Furthermore, we summarize the effects of variability in BP on CBF in older people. Of the various dynamic assessments of CA, a single sit-to-stand procedure is a feasible and physiologic method in the elderly. The collection of spontaneous beat-to-beat changes in BP and CBF allows estimation of CA using the technique of transfer function analysis. A thorough search of the literature yielded eight studies that have measured dynamic CA in the elderly aged <75 years. Regardless of the methods used, it was concluded from these studies that CA was preserved in this population.

Simultaneous measurements of cerebral oxygenation changes during brain activation by near‐infrared spectroscopy and functional magnetic resonance imaging in healthy young and elderly subjects

Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non‐invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor‐task‐related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 ± 9 years, mean ± SD) and five healthy elderly subjects (age 73 ± 3 years) by NIRS and blood‐oxygen‐level‐dependent (BOLD) fMRI simultaneously. The motor‐task consisted of seven cycles of 20‐sec periods of contralateral finger‐tapping at a rate as fast as possible alternated with 40‐sec periods of rest. Time‐locked averages over the seven cycles were used for further analysis. Task‐related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of −0.83 ± 0.38 μmol/L (P < 0.01) for the young and −0.32 ± 0.17 μmol/L (P < 0.05) for the elderly subjects. The BOLD‐fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 ± 0.72% (P < 0.01) for the young and 1.75 ± 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD‐fMRI measurements showed good correlation in the young (r = −0.70, r2 = 0.48, P < 0.001) and elderly subjects (r = −0.82, r2 = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age‐dependent decreases in task‐related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging. Hum. Brain Mapping 16:14–23, 2002.

No effect of one-year treatment with indomethacin on Alzheimer's disease progression: a randomized controlled trial.

Background The objective of this study was to determine whether treatment with the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows cognitive decline in patients with Alzheimers disease (AD). Methodology/Principal Findings This double-blind, randomized, placebo-controlled trial was conducted between May 2000 and September 2005 in two hospitals in the Netherlands. 51 patients with mild to moderate AD were enrolled into the study. Patients received 100 mg indomethacin or placebo daily for 12 months. Additionally, all patients received omeprazole. The primary outcome measure was the change from baseline after one year of treatment on the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary outcome measures included the Mini-Mental State Examination, the Clinicians Interview Based Impression of Change with caregiver input, the noncognitive subscale of the ADAS, the Neuropsychiatric Inventory, and the Interview for Deterioration in Daily life in Dementia. Considerable recruitment problems of participants were encountered, leading to an underpowered study. In the placebo group, 19 out of 25 patients completed the study, and 19 out of 26 patients in the indomethacin group. The deterioration on the ADAS-cog was less in the indomethacin group (7.8±7.6), than in the placebo group (9.3±10.0). This difference (1.5 points; CI −4.5–7.5) was not statistically significant, and neither were any of the secondary outcome measures. Conclusions/Significance The results of this study are inconclusive with respect to the hypothesis that indomethacin slows the progression of AD. Trial Registration ClinicalTrials.gov NCT00432081

Blood pressure reduction after oral glucose loading and its relation to age, blood pressure and insulin

Recently it was shown that blood pressure (BP) in the elderly may decrease after a meal. The pathophysiologic mechanism of this phenomenon is unknown. It has been suggested that a failure of insulin-mediated sympathetic nervous system activation plays a role. To evaluate the role of endogenous insulin, the effects of oral glucose and oral fructose loading on BP, heart rate and norepinephrine levels were studied in 10 young normotensive volunteers (YN), 10 young hypertensive patients (YH), 10 elderly normotensive volunteers (EN) and 10 elderly hypertensive patients (EH). Fructose, 75 g/300 ml of water, elicited--in contrast to the same amount of glucose--only a small increase in insulin and glucose levels. After glucose loading, mean arterial BP decreased by 17 mm Hg in the EH group (p less than 0.001), 6 mm Hg in the EN group (p less than 0.01) and 7 mm Hg in the YH group (p less than 0.001), and did not change in the YN group. After oral fructose loading, BP did not change in any group. In all groups except the YN group, the increases in norepinephrine level and heart rate after both tests were not significantly different. These findings suggest that the BP reduction after glucose loading is related to glucose-mediated factors. A failure of insulin-mediated sympathetic nervous system activation does not appear to play a major role.

Validation of Multi-Frequency Bioelectrical Impedance Analysis in Detecting Changes in Fluid Balance of Geriatric Patients

OBJECTIVES: Multi‐Frequency Bioelectrical Impedance Analysis (MFBIA) is a quick, simple, and inexpensive method to assess body fluid compartments. This study aimed at determining the validity of MFBIA in detecting clinically relevant changes of fluid balance in geriatric patients.

Furosemide Withdrawal in Elderly Heart Failure Patients With Preserved Left Ventricular Systolic Function

To explore the possibilities of furosemide withdrawal in elderly heart failure (HF) patients with intact left ventricular (LV) systolic function and assess its effects on functional status and orthostatic blood pressure homeostasis, we performed a placebo-controlled pilot trial of furosemide withdrawal with 3 months of follow-up in 32 HF patients (aged 75.1 +/- 0.7 years [mean +/- SEM]) with a LV ejection fraction of 60 +/- 2% and without overt congestion. Investigations included repeated clinical assessment, spirometry, standardized 6-minute walking test, and chest x-rays. Measurements of blood pressure response on active standing and Doppler echocardiography were performed before and 3 months after furosemide withdrawal. Recurrent congestive HF occurred in 2 of 21 patients (10%) who discontinued furosemide use, and in 1 of 11 patients (9%) who continued furosemide (p = NS). Three patients restarted furosemide for ankle edema and 1 for blood pressure levels >180/100 mm Hg. After 3 months, there were no differences regarding HF symptom scores, blood pressure, heart rate, spirometric results, 6-minute walking distance, or quality of life scores between patients who discontinued use and patients who continued the therapy. In patients successfully withdrawn, Doppler E/A ratio increased from 0.68 +/- 0.05 to 0.79 +/- 0.06 after withdrawal (p <0.01), and maximum blood pressure decrease on active standing changed from -8 +/- 5 mm Hg to +5 +/- 3 mm Hg systolic (p <0.05). Thus, in this pilot investigation of furosemide withdrawal in elderly HF patients without overt congestion and with a normal LV systolic function, withdrawal was successful in almost all patients and was associated with improvement of LV diastolic filling and blood pressure homeostasis on active standing.

Diuretic Usage and Withdrawal Patterns in a Dutch Geriatric Patient Population

OBJECTIVES: To describe diuretic usage and withdrawal patterns in a population of very old geriatric patients and to evaluate the long‐term probability of remaining free from diuretic therapy after withdrawal.

Reproducibility of cerebral blood volume measurements by near infrared spectroscopy in 16 healthy elderly subjects.

Near infrared spectroscopy (NIRS) is a non-invasive method to monitor cerebral haemodynamics. Used either alone or in combination with other non-invasive methods such as transcranial Doppler sonography, this technique is well suited for use in cerebrovascular research in ageing. Reproducibility of NIRS, however, has only been determined in neonates and adults. We applied controlled desaturation (the O(2)-method) to measure the cerebral blood volume (CBV) with NIRS in 16 healthy subjects aged 65 to 88. This method uses deoxygenated haemoglobin (the concentration of which is manipulated by desaturation) as an intravascular tracer for NIRS. We determined repeatability (between tests interval: 2 min), short-term reproducibility (intervals of 20 and 40 min) and long-term reproducibility (interval > 2 weeks). We found a coefficient of variation (CV) of 12.5% for repeatability and a CV of 11.7% for short-term reproducibility. The CV for long-term reproducibility was 15%. We conclude that NIRS can reproducibly measure CBV in subjects aged 65 and older, using the O(2)-method. In this group of healthy subjects, this method was well tolerated.

Loop diuretics in patients aged 75 years or older: general practitioners' assessment of indications and possibilities for withdrawal.

AbstractObjective: To examine the indications for prescription and possibilities for withdrawal of loop diuretics in community-dwelling patients aged 75 years or older, as reported by their general practitioners (GPs). Methods: Analysis of dispensary data to identify patients aged 75 years or older using loop diuretics on 1 February 1996. Questionnaires were sent to the GPs of these patients to inquire about the indications for loop diuretic prescription and the necessity for continuation. We subsequently determined loop diuretic prescription rates in the survey population over the next 9 months. Setting: A panel of nine Dutch community pharmacies. Results: Questionnaires were returned for 338 out of 667 patients (50.7%) using loop diuretics on 1 February 1996. Reported indications for loop diuretic use were heart failure in 223 patients (66.0%), hypertension in 35 patients (10.4%), and a combination of both in 23 patients (6.8%). Loop diuretics were used for ankle edema in 27 patients (8.0%) and for unknown reasons in another 27 patients (8.0%). Continuation of treatment was considered unnecessary by GPs in 66 out of 338 patients (19.5%). However, prescription rates for these 66 patients in the following months were no different from rates for the remaining 272 patients. Loop diuretics were still prescribed to 47 of 66 patients (71.2%) after 12 weeks, and to 26 patients (39.4%) after 36 weeks. Conclusions: GPs reported substantial opportunities for withdrawal of loop diuretics in patients over 75 years of age, but this did not influence actual prescription rates in these patients. Future studies should explore means of facilitating withdrawal of these medications in this population.

CAROTID SINUS SYNDROME: LOOKING SIDEWAYS IS SUFFICIENT CAUSE FOR SYNCOPE

1. The National Institute of Mental Health. Older Adults: Depression and Suicide Facts [on-line]. Available at www.nimh.nih.gov/publicat/elderlydepsuicide. cfm#4 Accessed May 4, 2004. 2. Schulz R, Beach SR, Ives DG et al. Association between depression and mortality in older adults. The Cardiovascular Health Study. Arch Intern Med 2000;160:1761–1768. 3. Matza LS, Revicki DA, Davidson JR et al. Depression with atypical features in the National Comorbidity Survey. Classification, description, and consequences. Arch Gen Psychiatry 2003;60:817–826. 4. Rinaldi P, Mecocci P, Benedetti C et al. Validation of the five-item geriatric depression scale in elderly subjects in three different settings. J Am Geriatr Soc 2003;51:694–698. 5. Ahmed A. Neutropenia associated with mirtazapine use: Is a drop in the neutrophil count in asymptomatic older adults a cause for concern? J Am Geriatr Soc 2002;50:1461–1463.