Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales.
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Samra Kiran, Macdougall Amy, Peakman Georgia, Bouzigues Arabella, Bocchetta Martina, Cash David M, Greaves Caroline V, Convery Rhian S, van Swieten John C, Jiskoot Lize C, Seelaar Harro, Moreno Fermin, Sánchez-Valle Raquel, Laforce Robert, Graff Caroline, Masellis Mario, Tartaglia Maria Carmela, Rowe James B, Borroni Barbara, Finger Elizabeth, Synofzik Matthis, Galimberti Daniela, Vandenberghe Rik, de Mendonca Alexandre, Butler Christopher R, Gerhard Alexander, Ducharme Simon, Le Ber Isabelle, Tiraboschi Pietro, Santana Isabel, Pasquier Florence, Levin Johannes, Otto Markus, Sorbi Sandro, Rohrer Jonathan D, Russell Lucy L, Genetic FTD Initiative (GENFI), Genetic FTDInitiative (GENFI)
Аннотация
METHODS: 832 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.
RESULTS: Overall, 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.
CONCLUSIONS: Neuropsychiatric 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.