In people who are aged >65 years, pharmacokinetics are influenced more by the loss of kidney function than by the aging process of any other organ. A GFR of 30 to 60 ml/min, suggestive of stage 3 kidney disease, is observed in 15 to 30% of elderly people. Drug dosing must be adjusted to both changing pharmacokinetics and pharmacodynamics; the pharmacodynamics might be influenced by the aging of other organs, too. Using our NEPharm database, we extracted abstracts with pharmacokinetic parameters since 1999 from a weekly PubMed search. The recorded data were analyzed and compared with published recommendations on drug dosage and use in the elderly. Purely age-related changes in pharmacokinetic parameters were recorded from publications on 127 drugs. The analysis of our NEPharm records revealed an average (mean ؎ SD) age-related prolongation of half-life of 1.39-fold (corresponding to ؉39 ؎ 61%). Contrasting to common opinion, mean changes in clearance (؊1 ؎ 54%) and volume of distribution (؉24 ؎ 56%) were even less. The modest changes in pharmacokinetics do not suggest general dosage modifications in the elderly for most drugs. Changes in pharmacodynamics justify the common medication rule in the elderly-"start low ؉ go slow"-especially for drugs that act on the central nervous system; however, in the case of anti-infective and anticancer therapy, the rule should be "hit hard ‫؍‬ start high ؉ go fast" to produce the target effect also in the elderly.

Unravelling the impact of genetic variants on clinical phenotypes is a challenging task. Apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) play an important role in cell growth, regeneration, synaptic plasticity, learning and memory processes. The aim of the present study was to examine the impact of BDNF Val66Met- and ApoE-polymorphisms and their interactions on hippocampal morphology and memory functions in healthy young adults. Hippocampal volume and memory performance of 135 healthy individuals, aged 24.6 ± 3.2 years, were assessed, using magnetic resonance imaging and the Inventory for Memory diagnostics. The performance of BDNF-Met66 carriers was significantly lower in working memory (P = 0.03) compared with non carriers, whereas no further differences were observed either in cognitive performance or in hippocampal volumes between the groups. Age, BDNF Val66 Met polymorphism and the interaction factor BDNF genotype x age were significantly associated with the variation of working memory scores (P = 0.01, 0.01, 0.02 respectively). No statistically significant differences were detected in the volumes of hippocampi and in memory phenotypes between individuals carrying the ApoE E4 allele and those without it. The analysis did not reveal an impact of gene-gene interaction between BDNF and ApoE genes on hippocampal volumes or memory performance. BDNF Val66Met polymorphism seems to influence working memory function and modulate the effects of ageing on working memory in healthy young adults.

Abstract.The apolipoprotein E (APOE) 4 allele is the major genetic risk factor for the development of late-onset Alzheimer's disease (AD), whereas the presence of the APOE 2 allele seems to confer protection. Here, we report that healthy young APOE 4 carriers have statistically significantly smaller hippocampal volumes than APOE 2 carriers, while no differences were detected between the two groups in memory performance. The difference in hippocampal morphology is cognitively/clinically silent in young adulthood, but could render APOE 4 carriers more prone to the later development of AD possibly due to lower reserve cognitive capacity.

These results demonstrate altered central opioidergic neurotransmission in CRPS. The correlation of regional opioid receptor availability to measures of pain, anxiety, and depression underlines the clinical importance of these findings.

We see the need for more knowledge-based information on drug dosing in patients with kidney impairment and those in the intensive care unit. The risk to life posed by underdosage might be underestimated, especially for anti-infective drugs.