Page 15 - jackie_poos
P. 15

consisting of a comprehensive neuropsychological assessment, physical examination, MRI of
               the brain, venipuncture and lumbar puncture at the Erasmus MC University Medical Center .
                                                                                       34
               Thus far, more than 200 participants have been included in this study. In 2012, the Genetic
               FTD Initiative (GENFI) started, an international multicenter study, in which currently 34   1
               academic centers across Europe and Canada, including the Erasmus MC University Medical
               Center, have recruited more than 1000 participants . The Longitudinal Evaluation of Familial
                                                       33
               Frontotemporal Dementia Subjects (LEFFTDS) and the Australian Dominantly Inherited Non-
               Alzheimer Dementias (DINAD), collaborate with GENFI within the FTD Prevention initiative
               (FPI) to align studies more closely and facilitate global clinical trials 28, 38 .


               These cohort biomarker studies in 50% at-risk individuals, have taught us that some individuals
               may experience significant psychological distress as a result of being at-risk. Individuals may
               choose to undergo predictive testing to determine if they are carriers of a mutation for FTD,
               with a positive test result implicating unavoidable approaching onset of a debilitating, fatal
               illness . As most of these individuals have first-hand experience with the consequences of
                    39
               the disease in close family members, this influences their views and plans for the future 39,
               40 . It is not surprising that carrying a mutation causative of FTD or the ambiguity of being at
               risk of such a mutation, without availability of a cure, can cause symptoms of anxiety and
               depression 41, 42 , similar to what has previously been demonstrated in familial AD dementia
               and HD 43-45 . In the absence of disease-modifying treatment, psychological interventions
               are necessary to reduce symptoms of anxiety and depression in presymptomatic mutation
               carriers and 50% at-risk individuals. Thus far no study has been published on psychological
               approaches in first-degree family members of patients with genetic FTD, but a mindfulness-
               based intervention has proven beneficial in premanifest HD individuals. The three core
               principles of mindfulness are 1) conscious awareness, 2) the present moment, and 3) a
               non-judgmental attitude. Mindfulness programs focus on cultivating these three aspects by
               performing meditation-based exercises, and special emphasis is given to accepting things as
               they are without trying to change them. The latter particularly makes this a promising avenue
               for populations with chronic diseases, including presymptomatic FTD mutation carriers and
               50% at-risk individuals for FTD.



               Outline of this thesis


               Currently, no cure exists for FTD but clinical trials testing new treatments are now underway
               and  sensitive  clinical  endpoints  to  monitor  treatment  response  are  urgently  needed.
               Furthermore,  diagnostic  accuracy  in  the  early  stages  of  the  disease  is  still  hampered
               by the wide range of overlapping clinical features between phenotypes, and with other
               neurodegenerative and psychiatric disorders, often causing a significant diagnostic delay.
               Therefore, the development and validation of novel sensitive cognitive markers for FTD to



               GENERAL INTRODUCTION                                                    13
   10   11   12   13   14   15   16   17   18   19   20