Majon Muller

Endogenous sex hormone levels and cognitive function in aging men Is there an optimal level

Objective: To determine whether endogenous sex hormone levels are associated with cognitive functioning in men. Methods: Cognitive performance was assessed in 400 independently living men between ages 40 and 80 in a population-based cross-sectional study. Compound scores were calculated for memory function, processing capacity/speed, and executive function. The Mini-Mental State Examination was used as a measure of global cognitive function. The adjusted association of testosterone (T) and estradiol (E2) (total, bioavailable) with neuropsychological test scores in the total group and in subgroups was assessed by linear and logistic regression analysis. Results: Curvilinear associations were observed between T and memory performance and processing capacity/speed, suggesting optimal sex hormone levels. No association between E2 and cognitive functioning was found. After the population was subdivided into four age decades, a linear association of T with cognitive functioning in the oldest age category remained. No association was found in the other age decades. Lower bioavailable T levels were associated with lower scores on processing capacity/speed and executive function; β (95% CI) values were 0.36 (0.07 to 0.66) and 0.17 (−0.01 to 0.35). Similar results were observed for total T. Conclusions: Higher testosterone (T) levels are associated with better cognitive performance in the oldest age category. Apparent curvilinear associations between T and certain cognitive functions in men suggest an optimal hormone level for particular cognitive tasks and are explained by linear associations in the oldest age category.

Cardiac disease and cognitive impairment: a systematic review

Cognitive impairment in cardiac patients may interfere with disease management. This review describes studies examining specific cognitive impairments in cardiac patients and studies that investigate the link between echocardiographic and cognitive measures. Executive function impairments were frequently reported in different patient groups. Also, lower cardiac output and worse left ventricular diastolic function are linked to executive function deficits. In cardiac patients, special attention should be paid to these executive function impairments in view of their role in disease management and independent living. Interventions that stimulate executive function should be encouraged and integrated in cardiac treatment protocols.

Hypertension and longitudinal changes in cerebral blood flow: The SMART-MR study

Cerebral hypoperfusion is among the mechanisms that may explain the association of high blood pressure (BP) with dementia. However, few data are available on the longitudinal association of hypertension and cerebral perfusion.

Treatment of Hypertension in the Oldest Old A Critical Role for Frailty

An 88-year-old woman with chronic hypertension was seen in the internal/geriatric medicine outpatient clinic. She had been treated for high blood pressure (BP) for ≈20 years with a low-dose thiazide, to which an angiotensin-converting enzyme-inhibitor had been added 5 years ago. In addition, after a possible transient ischemic attack 10 years ago, aspirin, omeprazole, and simvastatin had been added. She is known with mild cognitive impairment, which is stable with a mini-mental state examination score of 25, and a mild depression for which fluoxetine has been prescribed. In addition, she experienced 2 falls in the past 2 years; calcium/vitamin D and alendronate were started for the management of osteoporosis. On physical examination, she appears vital with a normal fluent gait and no signs of hemiparesis. Her BP is 165/75 mm Hg in the sitting position. Immediately after standing up from her chair, she feels dizzy for ≈10 seconds, but after 1 and 3 minutes, no orthostatic hypotension is found. Estimated glomerular filtration rate is 50 mL/min per 1.73 m2. Should antihypertensive treatment be intensified, left unaltered, or reduced? The oldest old, that is, persons aged ≥80 years, will be the fastest growing segment of the population for the next 40 years. By 2050, more than one quarter of all men and women aged ≥65 years in the Western world will be in the oldest old group.1 Despite longer life expectancy, the prevalence of various chronic diseases and functional impairment increases with age. As a result, populations of older individuals are often highly heterogeneous and individuals with same chronological age vary widely in health and functional ability. In other words, there is substantial heterogeneity in their biological age, and those at the higher end of biological age are often referred to as vulnerable or frail. BP rises with …

Prevalence and determinants for malnutrition in geriatric outpatients

BACKGROUND & AIMS Few data is available on the nutritional status of geriatric outpatients. The aim of this study is to describe the nutritional status and its clinical correlates of independently living geriatric older individuals visiting a geriatric outpatient department. METHODS From 2005 to 2010, all consecutive patients visiting a geriatric outpatient department in the Netherlands were screened for malnutrition. Nutritional status was assessed by the Mini Nutritional Assessment (MNA). Determinants of malnutrition were categorized into somatic factors (medicine use, comorbidity, walking aid, falls, urinary incontinence), psychological factors (GDS-15 depression scale, MMSE cognition scale), functional status (Activities of Daily Life (ADL), Instrumental ADL (IADL)), social factors (children, marital status), and life style factors (smoking, alcohol use). Univariate and multivariate logistic regression analyses, adjusted for age and sex and all other risk factors were performed to identify correlates of malnutrition (MNA < 17). RESULTS Included were 448 outpatients, mean (SD) age was 80 (7) years and 38% was men. Prevalence of malnutrition and risk for malnutrition were 17% and 58%. Depression, being IADL dependent, and smoking were independently associated with an increased risk of malnutrition with ORs (95%CI) of 2.6 (1.3-5.3), 2.8 (1.3-6.4), 5.5 (1.9-16.4) respectively. Alcohol use was associated with a decreased risk (OR 0.4 (0.2-0.9)). CONCLUSION Malnutrition is highly prevalent among geriatric outpatients and is independently associated with depressive symptoms, poor functional status, and life style factors. Our results emphasize the importance of integrating nutritional assessment within a comprehensive geriatric assessment. Future longitudinal studies should be performed to examine the effects of causal relationships and multifactorial interventions.

Alcohol consumption and arterial stiffness in men

Objective Moderate alcohol consumption has been proposed to be anti-atherogenic and protect against coronary heart disease. Arterial stiffness provides a summary measure of atherosclerotic arterial damage and cardiovascular risk. A vascular protective effect of moderate alcohol consumption would be reflected in an inverse association between alcohol intake and aortic stiffness. Design A cross-sectional study. Setting The male population of Utrecht. Participants Of 370 men, aged 40–80 years, alcohol intake was calculated from a standardized questionnaire and aortic stiffness was non-invasively assessed by pulse-wave velocity (PWV) measurement of the aorta. Results There were no non-drinkers; therefore the group consuming 0–3 glasses of alcoholic beverage per week was chosen as the reference group in the analyses. Those drinking 4–10, 11–21 and 22–58 glasses of alcoholic beverage per week had a −0.77 m/s (95% confidence interval, −1.26 to −0.28), −0.57 m/s (95% confidence interval, −1.07 to −0.08) and −0.14 m/s (95% confidence interval, −0.65 to 0.36) difference in mean PWV compared with those drinking 0–3 glasses per week. Adjustment for factors that correlated with PWV or alcohol consumption did not change the strength of the association. Conclusion Among men aged 40–80 years there is a J-shaped association between alcohol consumption and PWV. This further supports a decreased risk of cardiovascular disease with moderate alcohol consumption.

Specific risk factors for microbleeds and white matter hyperintensities in Alzheimer's disease.

We investigated whether microbleeds and white matter hyperintensities (WMH) in Alzheimers disease (AD) associate more with conventional vascular risk factors or with risk factors that reflect amyloid burden. A total of 371 patients with probable AD were included. WMH (Fazekas 2 or 3) were present in 107 (29%) patients and microbleeds were seen in 98 (26%). Patients with both microbleeds and WMH were older and presented more frequently with lacunes and multiple microbleeds than patients with microbleeds in isolation (all p < 0.05). Using multivariate regression models, we found that WMH presence showed independent associations with age, hypertension, current smoking, and lacune presence. Microbleeds were independently associated with male gender, higher blood pressure, lower cerebrospinal fluid Aβ42, and apolipoprotein E ε4 homozygosity. Separate analyses for microbleeds according to their location showed that these associations were driven by microbleeds in lobar locations. Our results suggest that, unlike WMH, microbleeds in AD are particularly associated with additional amyloid burden, and as such, may relate to cerebral amyloid angiopathy.

Blood pressure, cerebral blood flow, and brain volumes. The SMART-MR study

Background Low blood pressure (BP) has been related to increased risk of brain atrophy. As brain hypoperfusion might be a marker for impaired cerebral autoregulation, the risk of brain atrophy may be especially increased if BP is low in combination with brain hypoperfusion. We examined whether low BP was associated with brain atrophy and whether this association was stronger in patients with lower parenchymal cerebral blood flow (CBF), as an indicator of brain perfusion. Methods Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a cohort study among 1309 patients with atherosclerotic disease, cross-sectional analyses were performed in 965 patients (mean age 58 ± 10 years) with available BP and CBF measures. Parenchymal CBF was measured with magnetic resonance angiography and was expressed per 100 ml brain volume. Brain segmentation was used to quantify cortical gray matter volume and ventricular volume (% of intracranial volume). Results Linear regression analyses, adjusted for age, sex, and vascular risk factors showed that the association of systolic BP and pulse pressure, but not diastolic BP, with cortical gray matter volume was modified by parenchymal CBF (P interaction <0.05). In patients with lower parenchymal CBF, but not in those with high parenchymal CBF, lower systolic BP and pulse pressure (per SD decrease) were associated with reduced cortical gray matter volume: β (95% confidence interval) −0.29% (−0.63; 0.00) and −0.34% (−0.69; −0.01). Conclusion Our findings suggest that lower BP by itself is not sufficient to induce brain atrophy; however, lower SBP and lower pulse pressure in combination with lower parenchymal CBF increased the risk for cortical atrophy.

Vascular risk factors and cognitive function in a sample of independently living men

Decline of cognitive function with age may be due, in part, to atherosclerotic changes. The aim of the present study was to determine the relative contribution of vascular risk factors to cognitive functioning in a non-clinical sample of men. Cognitive tests were administered to 400 independently living men aged 40-80 years. The measures included short-term memory, speed of information processing, verbal and visual long-term memory, word fluency, cognitive flexibility, an estimate of verbal intelligence, and general cognitive status. Systolic blood pressure, serum cholesterol, glucose levels, smoking, alcohol intake, body mass index, homocysteine and peak expiratory flow rate were entered as independent variables into a multiple regression model, after adjustment for age and education. Hierarchical regression analyses revealed independent contributions of the combination of vascular risk factors in explaining the observed variance in performance on tests of cognitive functioning targeted at information processing capacity and speed and general cognitive status. Of the individual predictor variables, alcohol intake and homocysteine levels were significantly associated with processing capacity and speed, and peak expiratory flow rate was significantly associated with general cognitive status. Our results indicate that the combination of several independent vascular risk factors predicts performance on cognitive tests of information processing capacity and speed in a population-based sample of middle-aged and elderly men.

Prevalence of cortical superficial siderosis in a memory clinic population

Objective: To determine prevalence, topography, and severity of cortical superficial siderosis (SS), a recently recognized manifestation of cerebral amyloid angiopathy, and its possible association with Alzheimer disease (AD) in a memory clinic patient cohort. Methods: We included 809 patients (56% men, aged 66 ± 10 years) from the Amsterdam Dementia Cohort between November 2010 and November 2012 scanned on a 3-tesla MRI system. We analyzed prevalence and topography of cortical SS according to demographic, clinical, and MRI data. Agreement for SS detection between 2 neuroradiologists was calculated by using Cohen κ. Results: Agreement for detection of SS was excellent (unweighted κ of 0.81). In 17 patients (2.1%), cortical SS was found without a known cause. The prevalence of idiopathic SS differed according to diagnostic groups (p < 0.001): nearly 5% (95% confidence interval [CI] 2.8%–8.2%) in patients with AD (n = 168) vs 2% (95% CI 0.7%–6.0%) in patients with mild cognitive impairment (n = 143) and 2.5% (95% CI 0.7%–8.7%) in other types of dementia (n = 80). By contrast, SS was not found in patients with subjective complaints (n = 168) or in those with other disorders (n = 157). Presence of SS was associated with APOE ε4, microbleeds, and white matter hyperintensities (all p < 0.05) independent of diagnosis. Conclusion: The prevalence of cortical SS in a memory clinic setting is higher than reported in the general population but lower than reported in cerebral amyloid angiopathy. The relatively high prevalence of SS in AD suggests that SS is a relevant radiologic manifestation of amyloid pathology in AD. Presence of SS does not seem to predict severity of AD. Further longitudinal research is needed to investigate clinical relevance.