Cardiorespiratory Fitness Attenuates the Influence of Amyloid on Cognition.

The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-ß (Aß)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer's disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer's Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aß42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aß and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aß42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aß burden, that is, increased PiB-PET binding or reduced CSF Aß42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aß-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD.

Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease.

INTRODUCTION: Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer's disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer's disease (AD). METHODS: Eighty-six enrollees from the Wisconsin Registry for Alzheimer's Prevention participated in this study. Participants performed a graded maximal exercise test, underwent a T-1 anatomical magnetic resonance imaging scan, and completed the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: There were no significant relationships between CRF and HV or RAVLT memory scores for the entire sample. When the sample was explored on the basis of gender, CRF was significantly associated with hippocampal volume for women. For men, significant positive associations were observed between CRF and RAVLT memory scores. SUMMARY: These results suggest that CRF may be protective against both hippocampal volume and episodic memory decline in older adults at risk for AD, but that the relationships may be gender specific.

Chronotropic Response and Cognitive Function in a Cohort at Risk for Alzheimer's Disease.

The objective of this study was to examine the association of chronotropic response (CR) and heart rate (HR) recovery- two indices of cardiovascular function within the context of a graded exercise test- with cognitive performance in a cognitively healthy, late-middle-aged cohort at risk for Alzheimer's disease (AD). Ninety participants (age = 63.52±5.86 years; 65.6% female) from the Wisconsin Registry for Alzheimer's Prevention participated in this study. They underwent graded exercise testing and a comprehensive neuropsychological assessment that assessed the following four cognitive domains: Immediate Memory, Verbal & Learning Memory, Working Memory, and Speed & Flexibility. Regression analyses, adjusted for age, sex, and education, were used to examine the association between CR, HR recovery, and cognition. We found significant associations between CR and cognitive performance in the domains of Immediate Memory, Verbal Learning & Memory, and Speed & Flexibility. In contrast, HR recovery was not significantly associated with cognitive function. The association between CR and cognition persisted even after controlling for HR recovery. Together, these findings indicatethat, in a cognitively normal, late-middle-aged cohort, CR is a stronger correlate of cognitive performance than HR recovery. Overall, this study reinforces the idea that cardiovascular health plays an important role in cognitive function, specifically in a cohort at risk for AD; and that interventions that promote vascular health may be a viable pathway to preventing or slowing cognitive decline due to AD.

Classic intermittent claudication is an uncommon manifestation of lower extremity peripheral arterial disease in hospitalized patients with coronary artery disease.

Synchronous peripheral arterial disease (PAD) and coronary artery disease (CAD) is common. Standardized questionnaires such as the Rose/WHO questionnaire and later the Edinburgh modification of this questionnaire were developed to screen for PAD. Little data are available on the sensitivity of these questionnaires in hospitalized patients with CAD. The aim of this study was to determine the accuracy of these questionnaires and the prevalence of classic intermittent claudication in hospitalized patients with CAD. Medically stable patients with CAD were invited to participate before hospital discharge. The patients answered both the Rose/WHO and Edinburgh modification claudication questionnaires and had an ankle-brachial index (ABI) measured. An ABI less than or equal to 0.9 was considered to be indicative of significant PAD. Patients who had undergone previous lower extremity revascularization for PAD and had a corrected ABI greater than 0.9 were excluded. Ninety-five patients (66 men) were recruited. By measuring the ABI, 35 patients (25 men) were found to have significant PAD. An additional 3 patients who had an ABI corrected by lower extremity revascularization were excluded from the analysis. The Rose/WHO questionnaire had a sensitivity, specificity, and overall accuracy (95% CI) of 14.3% (2.7-25.9%), 96.7% (92.1-100%), and 66.3% (56.8-75.8%), respectively. The Edinburgh modification of the Rose/WHO questionnaire had a sensitivity, specificity, and overall accuracy (95% CI) of 28.6% (13.6-43.5%), 90.0% (82.4-97.6%), 67.4% (57.9-76.8%), respectively. Despite the high incidence of synchronous PAD in hospitalized patients with CAD, traditional claudication questionnaires are insensitive to PAD detection. Classic claudication is an uncommon manifestation of PAD in hospitalized patients with CAD.

Inaccuracy of lipid measurements with the portable Cholestech L.D.X analyzer in patients with hypercholesterolemia.

BACKGROUND: Although total cholesterol concentrations measured by portable lipid analyzers have acceptable bias and precision in young and middle-aged adults, clinically relevant differences in HDL-cholesterol (HDL-C) and triglyceride values have been described. Furthermore, the accuracy of portable lipid analyzers in older hyperlipidemic individuals, who have a high incidence of coronary heart disease, has not been validated. This study determined the biases and variability in portable lipid measurements in older patients with hypercholesterolemia and related them to National Cholesterol Education Program Adult Treatment Panel III guidelines. METHODS: Participants were > or =70 years of age with fasting serum LDL-cholesterol (LDL-C) concentrations > 1.40 g/L. Fasting fingerstick samples were analyzed on a Cholestech L.D.X desktop analyzer. Antecubital venous samples were analyzed in a proficiency-certified clinical laboratory. RESULTS: Portable measurements systematically overestimated triglycerides (0.296 g/L; P <0.001) and HDL-C (0.015 g/L; P = 0.026). LDL-C concentrations were underestimated (0.043 g/L; P = 0.046). Total and non-HDL cholesterol calculations based on the portable lipid device provided unbiased estimates, but wide variability was present. Significant variability in lipid determinations limited their clinical usefulness in individual patients, especially because 2 SD of the mean bias between the laboratory and the portable determinations of LDL-C and non-HDL cholesterol exceeded the 0.30 g/L cutoff that defines treatment targets in the current lipid guidelines. CONCLUSIONS: Lipid values obtained from portable lipid analyzers may be useful for screening, but they should not be used to make clinical decisions regarding the diagnosis and management of dyslipidemia in individual patients.

Lower extremity peripheral arterial disease in hospitalized patients with coronary artery disease.

The prevalence of coronary artery disease (CAD) in patients with peripheral arterial disease (PAD) has been well defined. However, the prevalence of PAD in hospitalized patients with CAD has not been defined. The ankle-brachial index (ABI) is a useful non-invasive tool to screen for PAD. The aim of our study was to assess the prevalence of PAD in hospitalized patients with CAD by measuring the ABI. The study was conducted at the University of Wisconsin Hospital and Clinics inpatient Cardiovascular Medicine Service. Medically stable patients with CAD were invited to participate prior to hospital discharge. Data regarding cardiovascular risk factors, history of previous PAD, physical examination, and ABI were collected. An ABI less than or equal to 0.9 or a history of previous lower extremity vascular invention was considered to be indicative of significant PAD. A total of 100 patients (66 men and 34 women) were recruited. Forty patients were found to have PAD (mean ABI in non-revascularized patients with PAD = 0.67). By measuring the ABI, 37 (25 men) were positive for PAD and three had an ABI corrected with previous revascularization. Of these patients, 21 (52.5%) had previously documented PAD. Patients with PAD were older (p = 0.003), had a greater smoking history (p = 0.002), were more likely to have diabetes (p = 0.012), hypertension (p = 0.013) and a trend towards more dyslipidemia (p = 0.055). In conclusion, hospitalized patients with CAD are likely to have concomitant PAD. Risk factors for PAD in this patient population include advanced age, history of smoking, diabetes, hypertension, dyslipidemia and abnormal pulse examination. Identification of patients with PAD by measuring the ankle-brachial index is easily done.