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consisting of a comprehensive neuropsychological assessment, physical examination, MRI of
the brain, venipuncture and lumbar puncture at the Erasmus MC University Medical Center .
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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
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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
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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