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BACKGROUND: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. METHODS: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. FINDINGS: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at

Patients with striate cortex damage and clinical blindness retain the ability to process certain visual properties of stimuli that they are not aware of seeing. Here we investigated the neural correlates of residual visual perception for dynamic whole-body emotional actions. Angry and neutral emotional whole-body actions were presented in the intact and blind visual hemifield of a cortically blind patient with unilateral destruction of striate cortex. Comparisons of angry vs. neutral actions performed separately in the blind and intact visual hemifield showed in both cases increased activation in primary somatosensory, motor, and premotor cortices. Activations selective for intact hemifield presentation of angry compared with neutral actions were located subcortically in the right lateral geniculate nucleus and cortically in the superior temporal sulcus, prefrontal cortex, precuneus, and intraparietal sulcus. Activations specific for blind hemifield presentation of angry compared with neutral actions were found in the bilateral superior colliculus, pulvinar nucleus of the thalamus, amygdala, and right fusiform gyrus. Direct comparison of emotional modulation in the blind vs. intact visual hemifield revealed selective activity in the right superior colliculus and bilateral pulvinar for angry expressions, thereby showing a selective involvement of these subcortical structures in nonconscious visual emotion perception.

Patients with striate cortex damage and clinical blindness retain the ability to process certain visual properties of stimuli that they are not aware of seeing. Here we investigated the neural correlates of residual visual perception for dynamic whole-body emotional actions. Angry and neutral emotional whole-body actions were presented in the intact and blind visual hemifield of a cortically blind patient with unilateral destruction of striate cortex. Comparisons of angry vs. neutral actions performed separately in the blind and intact visual hemifield showed in both cases increased activation in primary somatosensory, motor, and premotor cortices. Activations selective for intact hemifield presentation of angry compared with neutral actions were located subcortically in the right lateral geniculate nucleus and cortically in the superior temporal sulcus, prefrontal cortex, precuneus, and intraparietal sulcus. Activations specific for blind hemifield presentation of angry compared with neutral actions were found in the bilateral superior colliculus, pulvinar nucleus of the thalamus, amygdala, and right fusiform gyrus. Direct comparison of emotional modulation in the blind vs. intact visual hemifield revealed selective activity in the right superior colliculus and bilateral pulvinar for angry expressions, thereby showing a selective involvement of these subcortical structures in nonconscious visual emotion perception.