Fitness to drive of older drivers with cognitive impairments

Mensen worden ouder en blijven langer autorijden. Met de vergrijzing neemt ook het aantal mensen met dementie toe, en ook zij blijven graag mobiel. Veel patiënten met lichte dementie willen en kunnen blijven autorijden, maar het is voor een arts lastig om te bepalen wie er nog wel veilig rijdt en wie niet. In dit proefschrift wordt een nieuwe methode beschreven om de rijgeschiktheid te kunnen onderzoeken in een zorginstelling. Dit rijgeschiktheidsonderzoek bestaat uit interviews met de patiënt en een naaste, het uitvoeren van cognitieve testen en ritten in een rijsimulator. Met deze drie onderdelen werd voor meer dan 90% van de patiënten met de ziekte van Alzheimer juist voorspeld of ze de officiële rijtest op de weg van het CBR zouden halen. Hierbij spelen veel factoren een rol, zoals de ernst van de dementie, reactiesnelheid, kennis van de verkeersregels en het herkennen van gevaren in het verkeer. Voor patiënten met andere vormen van dementie (bijvoorbeeld vasculaire dementie, frontotemporale dementie en dementie met Lewy lichaampjes) zullen rijgeschiktheidsonderzoeken toegespitst op de betreffende vorm van dementie ontwikkeld moeten worden. De op basis van het onderzoek gegeven rijadviezen werden meestal opgevolgd, wat betekent dat de meeste patiënten met dementie die rijgeschikt zijn doorgaan met autorijden en de meeste patiënten die ongeschikt zijn stoppen met autorijden. Bij deze laatste groep is ondersteuning bij het vinden van alternatieve vervoerswijzen belangrijk, zodat mobiliteit en sociale participatie zoveel mogelijk behouden kunnen blijven

Assessing fitness to drive:A validation study on patients with mild cognitive impairment

Objectives: There is no consensus yet on how to determine which patients with cognitive impairment are able to drive a car safely and which are not. Recently, a strategy was composed for the assessment of fitness to drive, consisting of clinical interviews, a neuropsychological assessment, and driving simulator rides, which was compared with the outcome of an expert evaluation of an on-road driving assessment. A selection of tests and parameters of the new approach revealed a predictive accuracy of 97.4% for the prediction of practical fitness to drive on an initial sample of patients with Alzheimer's dementia. The aim of the present study was to explore whether the selected variables would be equally predictive (i.e., valid) for a closely related group of patients; that is, patients with mild cognitive impairment (MCI).Methods: Eighteen patients with mild cognitive impairment completed the proposed approach to the measurement of fitness to drive, including clinical interviews, a neuropsychological assessment, and driving simulator rides. The criterion fitness to drive was again assessed by means of an on-road driving evaluation. The predictive validity of the fitness to drive assessment strategy was evaluated by receiver operating characteristic (ROC) analyses.Results: Twelve patients with MCI (66.7%) passed and 6 patients (33.3%) failed the on-road driving assessment. The previously proposed approach to the measurement of fitness to drive achieved an overall predictive accuracy of 94.4% in these patients. The application of an optimal cutoff resulted in a diagnostic accuracy of 100% sensitivity toward unfit to drive and 83.3% specificity toward fit to drive. Further analyses revealed that the neuropsychological assessment and the driving simulator rides produced rather stable prediction rates, whereas clinical interviews were not significantly predictive for practical fitness to drive in the MCI patient sample.Conclusions: The selected measures of the previously proposed approach revealed adequate accuracy in identifying fitness to drive in patients with MCI. Furthermore, a combination of neuropsychological test performance and simulated driving behavior proved to be the most valid predictor of practical fitness to drive.</p

Adherence to driving cessation advice given to patients with cognitive impairment and consequences for mobility

Background: Driving is related to social participation; therefore older drivers may be reluctant to cease driving. Continuation of driving has also been reported in a large proportion of patients with cognitive impairment. The aim of this study is to investigate whether patients with cognitive impairment adhere to driving cessation advice after a fitness-to-drive assessment and what the consequences are with regard to mobility. Methods: Patients with cognitive impairment (n= 172) participated in a fitness-to-drive assessment study, including an on-road driving assessment. Afterwards, patients were advised to either continue driving, to follow driving lessons, or to cease driving. Approximately seven months thereafter, patients were asked in a follow-up interview about their adherence to the driving recommendation. Factors influencing driving cessation were identified using abinary logistic regression analysis. Use of alternative transportation was also evaluated. Results: Respectively 92 and 79% of the patients adhered to the recommendation to continue or cease driving. Female gender, a higher Clinical Dementia Rating-score, perceived health decline, and driving cessation advice facilitated driving cessation. Patients who ceased driving made use of less alternative modes of transportation than patients who still drove. Nonetheless, around 40% of the patients who ceased driving increased their frequency ofcycling and/or public transport use. Conclusions: Adherence to the recommendations given after the fitness-to-drive assessments was high. Female patients were in general more likely to cease driving. However, a minority of patients did not adhere to driving cessation advice. These drivers with dementia should be made aware of the progression of their cognitive impairment and general health decline to facilitate driving cessation. There are large differences in mobility between patients with cognitive impairment. Physicians should discuss options for alternative transportation in order to promote sustained safe mobility of patients with cognitive impairment

Constitutively active GSK3 beta as a means to bolster dendritic cell functionality in the face of tumor-mediated immune suppression

In patients with cancer, the functionality of Dendritic Cells (DC) is hampered by high levels of tumor-derived suppressive cytokines, which interfere with DC development and maturation. Poor DC development can limit the efficacy of immune checkpoint blockade and in vivo vaccination approaches. Interference in intracellular signaling cascades downstream from the receptors of major tumor-associated suppressive cytokines like IL-10 and IL-6, might improve DC development and activation, and thus enhance immunotherapy efficacy. We performed exploratory functional screens on arrays consisting of >1000 human kinase peptide substrates to identify pathways involved in DC development and its inhibition by IL-10 or IL-6. The resulting alterations in phosphorylation of the kinome substrate profile pointed to glycogen-synthase kinase-3 beta (GSK3 beta) as a pivotal kinase in both DC development and suppression. GSK3 beta inhibition blocked human DC differentiation in vitro, which was accompanied by decreased levels of IL-12p70 secretion, and a reduced capacity for T cell priming. More importantly, adenoviral transduction of monocytes with a constitutively active form of GSK3 beta induced resistance to the suppressive effects of IL-10 and melanoma-derived supernatants alike, resulting in improved DC development, accompanied by up-regulation of co-stimulatory markers, an increase in CD83 expression levels in mature DC, and diminished release of IL-10. Moreover, adenovirus-mediated intratumoral manipulation of this pathway in an in vivo melanoma model resulted in DC activation and recruitment, and in improved immune surveillance and tumor control. We propose the induction of constitutive GSK3 beta activity as a novel therapeutic means to bolster DC functionality in the tumor microenvironment.Peer reviewe

Shifting from manual to automatic gear when growing old: good advice?:Results from a driving simulator study

Older people may be advised to switch from manual to automatic gear shifting, because they may have difficulties with dividing their attention between gear shifting and other driving tasks such as perceiving other traffic participants. The question is whether older drivers show a better driving performance when using automatic gear shifting instead of manual gear shifting. Twenty young and twenty older drivers participated in a driving simulator study. Each participant drove both in the manual and the automatic gear conditions. Young drivers reported significantly higher risk taking behaviour in traffic than the older drivers. The older drivers experienced more collisions in the driving simulator than the young participants, but this was only true in the manual gear condition. Older participants swerved more than young participants in both gear conditions. Altogether, the driving performance of the older drivers was better in the automatic gear condition compared with the manual gear condition. This research supports the advice for older drivers to use automatic gear shifting