Objective: To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared to age-matched control subjects. Methods: From a randomized controlled trial (PROSPER study), a study sample of 89 patients with DM and 438 control subjects without DM aged 70–82 years were included for brain MRI scanning and cognitive function testing at baseline and reexamination after 3 years. Changes in brain atrophy, white matter hyperintensities (WMHs), number of infarctions, and cognitive function test results were determined in patients with DM and subjects without DM. Linear regression analysis was performed with correction for age, gender, hypertension, pravastatin treatment, educational level, and baseline test results. In patients with DM, baseline MRI parameters were correlated with change in cognitive function test result using linear regression analysis with covariates age and gender. Results: Patients with DM showed increased progression of brain atrophy (p < 0.01) after follow-up compared to control subjects. No difference in progression of WMH volume or infarctions was found. Patients with DM showed increased decline in cognitive performance on Stroop Test (p = 0.04) and Picture Learning Test (p = 0.03). Furthermore, in patients with DM, change in Picture Learning Test was associated with baseline brain atrophy (p < 0.02). Conclusion: Our data show that elderly patients with DM without dementia have accelerated progression of brain atrophy with significant consequences in cognition compared to subjects without DM. Our findings add further evidence to the hypothesis that diabetes exerts deleterious effects on neuronal integrity.
High BP is associated with decline of renal function. Whether this is true for very old people largely is unknown. Therefore, this study assessed the effect of BP on creatinine clearance over time in very old participants. A total of 550 inhabitants (34% men) of Leiden, The Netherlands, were enrolled in a population-based study at their 85th birthday and followed until death or age 90. BP was measured twice at baseline and at age 90 yr. Creatinine clearance was estimated annually (Cockcroft-Gault formula). The mean creatinine clearance at baseline was 45.4 ml/min (SD 11.5). Systolic BP was not associated with changes in creatinine clearance during follow-up. Those with diastolic BP (DBP) <70 mmHg had an accelerated decline of creatinine clearance (1.63 ml/min per yr) compared with those with DBP between 70 and 79 mmHg (1.21 ml/min per yr; P = 0.01), 80 to 89 mmHg (1.26 ml/min per yr; P = 0.03), and >89 mmHg (1.38 ml/min per yr; P = 0.32). Participants with a decline in systolic BP during follow-up had an accelerated decline of creatinine clearance compared with those with stable BP (1.54 [SE 0.09] versus 0.98 ml/min per yr [SE 0.09]; P < 0.001). Similar results were found for a decline in DBP (1.54 [SE 0.10] versus 1.06 ml/min per yr [SE 0.08]; P < 0.001). In the oldest individual, high BP is not associated with renal function. In contrast, low DBP is associated with an accelerated decline of renal function. The clinical implications of these findings have to be studied.
The main causes of dementia at old age are Alzheimer's disease and vascular dementia. The clinical presentations of late-onset Alzheimer's disease and vascular dementia can barely be differentiated. This clinical observation is supported by pathological findings. Late-onset dementia should be considered a multifactorial disease, in which both vascular factors and amyloid dispositions contribute to cognitive decline.
The study aim was to investigate whether cognitive impairment, measured by the Six-Item Cognitive Impairment Test (6-CIT), is an independent predictor of adverse outcomes in acutely hospitalized older patients.This was a prospective multicenter study including acutely hospitalized patients aged 70 years and older. Multivariable logistic regression was used to investigate whether impaired cognition (6-CIT ≥11 points) was an independent predictor of 90-day adverse outcome, a composite measure of functional decline and mortality. Secondary endpoints were hospital length of stay, new institutionalization, and in-hospital mortality.In total, 196 (15.6%) of 1,252 included patients had a 6-CIT ≥11. Median age was 80 years (interquartile range 74-85). Patients with impaired cognition had higher rates of 90-day adverse outcome (41.7% compared to 30.3% in 1,056 not cognitively impaired patients, p = 0.009). Impaired cognition was a predictor of 90-day adverse outcome with a crude odds ratio (OR) of 1.64 (95% CI 1.13-2.39), but statistical significance was lost when fully corrected for possible confounders (OR 1.44, 95% CI 0.98-2.11). For all secondary outcomes, impaired cognition was an independent predictor.In the acute hospital setting, the 6-CIT is associated with 90-day adverse outcome and is an independent predictor of hospital length of stay, new institutionalization, and in-hospital mortality.
Both acetylcholine (ACh) and 5-hydroxytryptamine (5HT) are used to examine nitric oxide (NO)-mediated vasodilatation in humans. Animal data suggest that both substances can also induce the release of prostacyclin (PGI2). This study was designed to investigate the role of the prostaglandin pathway in Ach- and 5HT-induced vasodilation in humans. The experiments were done in three groups of healthy male volunteers. In group 1 (n = 6), ACh (100–1,000 ng/kg/min) and sodium-nitroprusside (10–100 ng/kg/min) were infused into the brachial artery alone, together with a continuous infusion of indomethacin (1.3 μg/kg/min) and during a combined infusion of indomethacin and the competitive NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA; 30 μg/kg/min). In group 2 (n = 5), 5HT (0.3–1.0 ng/kg/min) was infused alone and together with a continuous infusion of indomethacin and l-NMMA. In group 3 (n = 6), the synthetic prostaglandin analog iloprost (0.5–4.5 ng/kg/min) was infused together with a continuous infusion of saline, l-NMMA, and l-NMMA with indomethacin, respectively. The infusions of indomethacin and l-NMMA started 10 min before the infusion of ACh, 5HT, iloprost, and sodium nitroprusside. Forearm blood flow was measured using computerized venous occlusion plethysmography. Both the Ach- and 5HT-induced vasodilator responses were significantly attenuated by indomethacin (p < 0.05 for both), but not further influenced by a concomitant infusion of l-NMMA. The vasodilatation induced by iloprost was significantly inhibited by l-NMMA (p < 0.05) and not affected by indomethacin. The sodium nitroprusside–induced vasodilation was influenced by neither l-NMMA nor indomethacin. It is concluded that in the human forearm, the prostaglandin pathway is involved in both the Ach- and 5HT-induced NO-mediated vasodilatation.
Low wall shear stress (WSS) is an early marker in the development of vascular lesions. The present study aims to assess the relationship between diastolic and systolic WSS in the internal carotid artery and periventricular (PWML), deep white matter lesions, and cerebral infarcts (CI).Early, mid, and late diastolic and peak systolic WSS were derived from shear rate obtained by gradient echo phase contrast magnetic resonance sequences multiplied by individually modeled viscosity. PWML, deep white matter lesions, and CI were derived from proton density (PD), T2, and fluid attenuated inversion recovery (FLAIR) MRI in 329 participants (70-82 years; PROSPER baseline). Analyses were adjusted, if appropriate, for age, gender, intracranial volume, and multiple cardiovascular risk factors.Mid-diastolic WSS was significantly correlated with the presence of PWML (B=-10.15; P=0.006) and CI (B=-2.06; P=0.044), but not with deep white matter lesions (B=-1.30; P=0.050; adjusted for age, gender, WML, and intracranial volume). After adjustment for cardiovascular risk factors, these correlations weakened but remained significant. Systolic WSS was not correlated with any of the cerebrovascular parameters.This study is the first to our knowledge to present a cross-sectional correlation between carotid artery WSS and cerebrovascular pathology such as PWML and CI in a large population. Furthermore, it shows that diastolic hemodynamics may be more important than systolic or mean hemodynamics. Future studies exploring vascular hemodynamic damage should focus on diastolic WSS.
<i>Background: </i>To define the cardiovascular risk factors for cerebral microbleeds and to investigate the relationship between microbleeds on the one hand, and the volume of age-related white matter hyperintensities (WMH) and atrophy on the other in an elderly population. <i>Methods:</i> Four hundred and thirty-nine elderly subjects (age range: 72–85; mean: 77) suffering from vascular disease or at high risk for developing this condition were included in this study. For each subject the number and localization of the microbleeds was recorded. <i>Results:</i> The prevalence of microbleeds in this study was 24%. We found age and a history of hypertension to be risk factors for microbleeds. After regional subdivision systolic blood pressure was found to be a risk factor for microbleeds located in the basal ganglia. A history of hypertension was more prevalent in patients with corticosubcortical and basal ganglia microbleeds. Magnetic resonance imaging risk factors associated with one or more microbleeds were total WMH volume, subcortical WMH volume, and periventricular WMH volume. Total WMH volume and periventricular WMH volume were risk factors for corticosubcortical microbleeds and basal ganglia microbleeds. <i>Conclusion:</i> A high prevalence of microbleeds was found in a population of patients suffering from vascular disease or at high risk for developing this condition. Age, hypertension and WMH were the most important risk factors for microbleeds, especially when located in the corticosubcortial junction or in the basal ganglia.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)