Géraud Dautzenberg

Summary and general discussion

subsided. This method is often used in clinical practice, although it has not been proven whether it is the correct means to distinguish between a lowMoCA score due to psychiatric causes and a low MoCA due to neurodegenerative causes. Another subject that must be studied further is combining the MoCA with other ‘bedside’ assessments measuring other aspects of the diseases to improve accuracy, but not the cost in time or budget. In addition, bedside tests often require less-trained staff. This is, next to budget, a major issue in the near future, as fewer specialised staff are expected in proportion to the number of patients due to demographic changes. The clinical implications of the study on valproic acid were not only to learn from our mistakes but also to warn others. Furthermore, it also changed the protocol of the request for concertation for valproic acid at our hospital and in the region. Ever since our publication, albumin blood levels are always measured when the total concentration of valproic acid is monitored. In addition, it has become easier to request a free blood concentration in the laboratory these days with less argumentation. Of course, it would be better to add the free valproic acid level from the beginning, as it is the standard in some countries, such as Japan. This decision is for health policymakers to make, as it comes with some extra cost. However, the implemented new policy of adding albumin blood levels will not avoid all unseen and avoidable side effects of elevated free valproic acid levels. We still recommend measuring free valproic acid levels, especially in the older adult population. The albumin level itself is also relative. The literature mentions a lower binding capacity of albumin in older adults, next to the effect of other medications that have a higher affinity for binding to albumin, such as NSAIDs. This increases the free fraction of valproic acid and the risk of side effects. Even if the clinician is aware of the side effects of valproic acid, the following case is easy to imagine: a patient of age who used valproic acid for years recently starts to complain about cognitive impairment. He asks his doctor, if at all this could be due to the use of valproic acid. If the total valproic acid blood concentration stayed the same an understandable reaction of the doctor would be ‘if the side effects did not start at the start of the treatment; there is a very low likelihood that it will emerge only after years’. Even so, if the doctor is willing to check the valproic acid level (as it should be routinely) to exclude a rise, she will get the total blood level. This can be the same for all the previous concentrations. Even with a normal albumin value accompanying the therapeutic total valproic acid concentration, the free valproic acid concentration can still be elevated owing to lower binding capacity because of age or other medications. The reason for the cognitive impairment remains unnoticed and is likely attributed to age or (if they have read this

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