Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales
Creators: name: Samra, Kiran
name: Macdougall, Amy
name: Peakman, Georgia
name: Bouzigues, Arabella
name: Bocchetta, Martina
name: Cash, David M
name: Greaves, Caroline V
name: Convery, Rhian S
name: Van Swieten, John C
name: Jiskoot, Lize C
name: Seelaar, Harro
name: Moreno, Fermin
name: Sánchez-Valle, Raquel
name: Laforce, Robert
name: Graff, Caroline
name: Masellis, Mario
name: Tartaglia, Maria Carmela
name: Rowe, James B
name: Borroni, Barbara
name: Finger, Elizabeth
name: Synofzik, Matthis
name: Galimberti, Daniela
name: Vandenberghe, Rik
name: De Mendonca, Alexandre
name: Butler, Christopher R
name: Gerhard, Alexander
name: Ducharme, Simon
name: Le Ber, Isabelle
name: Tiraboschi, Pietro
name: Santana, Isabel
name: Pasquier, Florence
name: Levin, Johannes
name: Otto, Markus
name: Sorbi, Sandro
name: Rohrer, Jonathan D
name: Russell, Lucy L
Publisher: name: Universität Ulm
Year: 2023
Subjects: subject: FRONTOTEMPORAL DEMENTIA
subject: GENETICS
subject: NEUROPSYCHIATRY
subject: HEXANUCLEOTIDE REPEAT EXPANSION
subject: AMYOTROPHIC-LATERAL-SCLEROSIS
subject: PSYCHIATRIC-SYMPTOMS
subject: C9ORF72
subject: DIAGNOSIS
subject: CRITERIA
subject: PROGRESSION
subject: PREVALENCE
subject: PHENOTYPE
subject: MUTATION
subject: DDC 610 / Medicine &amp; health

description: BackgroundCurrent clinical rating scales in frontotemporal dementia (FTD) often do not incorporate neuropsychiatric features and may therefore inadequately measure disease stage.Methods832 participants from the Genetic FTD Initiative (GENFI) were recruited: 522 mutation carriers and 310 mutation-negative controls. The standardised GENFI clinical questionnaire assessed the frequency and severity of 14 neuropsychiatric symptoms: visual, auditory, and tactile hallucinations, delusions, depression, anxiety, irritability/lability, agitation/aggression, euphoria/elation, aberrant motor behaviour, hypersexuality, hyperreligiosity, impaired sleep, and altered sense of humour. A principal component analysis (PCA) was performed to identify key groupings of neuropsychiatric and behavioural items in order to create a new neuropsychiatric module that could be used as an addition to the Clinical Dementia Rating (CDR) plus National Alzheimer’s Coordinating Center Behaviour and Language Domains (NACC FTLD) rating scale.ResultsOverall, 46.4% of mutation carriers had neuropsychiatric symptoms (51.6% C9orf72, 40.8% GRN, 46.6% MAPT) compared with 24.5% of controls. Anxiety and depression were the most common in all genetic groups but fluctuated longitudinally and loaded separately in the PCA. Hallucinations and delusions loaded together, with the remaining neuropsychiatric symptoms loading with the core behavioural features of FTD. These results suggest using a single ‘psychosis’ neuropsychiatric module consisting of hallucinations and delusions. Adding this to the CDR plus NACC FTLD, called the CDR plus NACC FTLD-N, leads to a number of participants being scored more severely, including those who were previously considered asymptomatic now being scored as prodromal.ConclusionsNeuropsychiatric symptoms occur in mutation carriers at all disease stages across all three genetic groups. However, only psychosis features provided additional staging benefit to the CDR plus NACC FTLD. Inclusion of these features brings us closer to optimising the rating scale for use in trials.