Aging is known to be associated with an increased prevalence of multiple chronic diseases, which frequently causes the use of complex therapeutic regimens. The aging process is characterized by relevant changes in drug handling, physiological reserve, and pharmacodynamic response. Hepatic drug clearance of several drugs decreases with aging, mainly due to reduced blood flow, and hepatocyte mass. Renal function also declines with aging, mainly due to sclerotic changes in the glomeruli. Furthermore, due to reduced muscle mass, older subjects frequently have depressed glomerular filtration rate despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly the clearance of hydrosoluble drugs. Changes in pharmacodynamics are also well documented in the cardiovascular and nervous system. Age-related changes in pharmacokinetics and pharmacodynamics, together with comorbidity and polypharmacy, make elderly patients at special risk for advers drug reactions, which in turn are cause of relevant health burden and costs. Selected measures can assist in preventing or detecting timely such adverse events.

THE GRAPHED relationship of body weight to mortality throughout the range of body mass index (weight in kilograms divided by the square of the height in meters [BMI]) has been described as J-shaped, U-shaped, inverse, positive, and even absent.^1-6 In most population studies, the association between BMI and mortality is described by a U-shaped curve, with augmented risk in the lowest and highest percentiles of the distribution, even when controlling for comorbid disease, age, and smoking.⁷ However, the association between body weight and mortality remains controversial.⁸ In particular, important questions remain about the impact of age on the relationship between overweight conditions and mortality.^9-11 The third edition of the Dietary Guidelines for Americans¹² has recommended a higher BMI with increasing age. On the contrary, the last edition of analogous weight guidelines¹³ did not include age-specific recommendations.

Background: Arterial hypotension has been associated with increased risk of dementia in some large prospective studies; and cognitive impairment is common among elderly with left ventricular function. The authors assessed whether arterial hypotension might be associated with cognitive impairment among older subjects with heart failure. Methods: This study involved all 13,635 patients (of whom 1,583 had heart failure) without cerebrovascular disease or AD, admitted to 81 Italian academic hospitals in 1995 and 1997. The association between blood pressure and cognitive impairment (as indicated by a Hodkinson Mental Test score < 7) according to the presence of heart failure was assessed by univariate analyses, including linear discriminant analysis. This association was also verified by multivariate analyses after stratifying for diagnosis of heart failure. Results: Cognitive impairment was found in 26% of patients with heart failure and in 19% of remaining subjects (Fisher exact p < 0.0001). Blood pressure levels did not differ according to diagnosis of heart failure, but discriminant analysis indicated that systolic blood pressure levels below 130 mm Hg predicted cognitive impairment only among participants with heart failure. Among such participants, systolic blood pressure was associated with cognitive impairment in multiple logistic regression modeling (for 10 mm Hg intervals, OR = 0.78; 95% CI = 0.71 to 0.86). Again, this association was not found among participants without heart failure. Conclusions: Systolic hypotension is selectively associated with cognitive impairment in older patients with heart failure. As early treatment of cardiac low-output states can reverse cognitive dysfunction, the routine management of heart failure should include systematic assessment of cognitive performance.