Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study.
Premi E., Pengo M., Mattioli I., Cantoni V., Dukart J., Gasparotti R., Buratti E., Padovani A., Bocchetta M., Todd EG., Bouzigues A., Cash DM., Convery RS., Russell LL., Foster P., Thomas DL., van Swieten JC., Jiskoot LC., Seelaar H., Galimberti D., Sanchez-Valle R., Laforce R., Moreno F., Synofzik M., Graff C., Masellis M., Tartaglia MC., Rowe JB., Tsvetanov KA., Vandenberghe R., Finger E., Tiraboschi P., de Mendonça A., Santana I., Butler CR., Ducharme S., Gerhard A., Levin J., Otto M., Sorbi S., Le Ber I., Pasquier F., Rohrer JD., Borroni B., Genetic Frontotemporal dementia Initiative (GENFI) None.
BACKGROUND: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. METHODS: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. RESULTS: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p