In Switzerland, approximately 350,000 people aged 70 years or older own a valid driving license. By law, these drivers are medically assessed every other year, most commonly by their general practitioner, to exclude that a medical condition is interfering with their driving skills. A prerequisite for driving is the integration of high-level cognitive functions with perception and motor function. Ageing, per se, does not necessarily impair driving or increase the crash risk. However, medical conditions, such as cognitive impairment and dementia, become more prevalent with advancing age and may contribute to poor driving and an increased crash risk. The extent to which driving skills are impaired depends on the cause of dementia, disease severity, other co-morbidities and individual compensation strategies. Dementia often remains undiagnosed and therefore general practitioners (GPs) can find themselves in the difficult situation to disclose a suspicion about cognitive impairment and queries about medical fitness to drive, at the same time. In addition, the literature suggests that cognitive screening tests, most commonly used by GPs, have a limited role in judging whether an older person remains fit to drive. Further specialist assessment, for example in a memory clinic or on the road testing (ORT), may be helpful when the diagnosis or its implication for driving remain unclear. Here, we review the literature about cognition and driving, for GPs who advise older drivers who wish to continue driving.

Human GH is encoded by the GH-1 gene which belongs to the GH gene cluster encompassing a distance of about 65 kb on the long arm of chromosome 17. Familial isolated growth hormone deficiency (IGHD) is associated with at least four Mendelian disorders. These include two forms that have autosomal recessive inheritance (IGHD types IA and IB) as well as autosomal dominant (IGHD type II) and X-linked (IGHD III) forms. The aim of our study was to evaluate the prevalence of all GH-1 gene alterations by sequencing the whole GH-1 gene after PCR amplification among 151 affected subjects from 83 families with severe IGHD (height: <-4.5 SD score). A high frequency of GH-1 gene alterations was found in families with IGHD type IA (8/12, 66.7%), whereas only a low frequency of GH-1 gene defects was present in all the other GH-deficient families (7/71, 9.9%). The absolute frequency of GH-1 gene deletions was 8.7% (6/69), 11.8% (4/34), and 18.7% (9/48) in Northern Europeans, Mediterraneans, and Asians, respectively, giving an overall frequency of 12.5% (19/151). The sizes of the deletions were heterogeneous with the most frequent (78%) being 6.7 kb. In addition, 6% (9/151) of the patients presented GH-1 gene mutations such as frameshift, stop codon and splicing error. Furthermore, total GH-1 gene abnormalities varied among different populations from 11.6% in Northern Europe, 14.7% in Mediterranean countries and 31.2% in Asia. Most striking, however, was the low frequency rate of 1.7% (2/119) of GH-1 gene mutations responsible for the most common phenotype of IGHD, namely type IB, among the subjects characterized by the production of deficient but detectable amounts of GH after provocative stimuli. This finding underlines the necessity to focus rather on the promoter region of the GH-1 gene (cis-acting elements and trans-acting factors), and on other candidate genes specific for the GH axis than the GH-1 gene itself to define genetically the IGHD type IB phenotype in more detail.

The Pra instrument exhibits good validity for predicting future health service use on a population level in different healthcare settings. Administrative data have shown similar predictive validity, but in practice, such data are often not available. The Pra is likely of high interest to governments and health insurance companies worldwide as a basis for programs aimed at health risk management in older persons.

Objective: Isolated growth hormone deficiency (IGHD) type IB is suggested to be more probably due to alterations in the genes directly involved in the hypothalamo-pituitary axis and/or in the specific transcriptional regulation (cis-trans coupling) of the hGH-1 gene than to alterations in the gene itself. In this study we analyzed the hGH-1 gene promoter region for structural alterations and allelic variations. Methods:The hGH-1 gene promoter region was analyzed by PCR, cycle sequencing and direct-blotting electrophoresis in a total of 212 individuals including 113 patients with IGHD type IB, 21 unaffected family members and 78 normal controls. Results: Twenty-two sequence variation sites were identified. Of these, 14% were located around the region of ¹1075bp, 77% between ¹550bp and the translational start site (þ1bp) and 9% within the first intron. Only one variation site affected a characterized cis-acting element, namely that of NF-1. Importantly, all the variations found in patients were also observed in non-affected family members as well as in normal unrelated controls. Conclusions: These findings imply that it is not a single variation within the GH-1 gene promoter, and therefore in the cis-acting elements, which causes IGHD. However, we can not exclude the possibility that combinations of variations might perturb expression. Furthermore, these data illustrate the normal heterogeneity of the GH-1 gene promoter region, a fact that has to be borne in mind whenever transcriptional studies are performed. European Journal of Endocrinology 137 474-481