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 death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0•45 between individual and parental age at onset, r=0•63 between individual and mean family age at onset, r=0•58 between individual and parental age at death, and r=0•69 between individual and mean family age at death) than in either the C9orf72 group (r=0•32 individual and parental age at onset, r=0•36 individual and mean family age at onset, r=0•38 individual and parental age at death, and r=0•40 individual and mean family age at death) or the GRN group (r=0•22 individual and parental age at onset, r=0•18 individual and mean family age at onset, r=0•22 individual and parental age at death, and r=0•32 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35-62, for age at onset; 61%, 47-73, for age at death), and even mor...

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Background: For the early diagnosis of Parkinson disease dementia (PDD), objective home-based tools are needed to quantify even mild stages of dysfunction of the activities of daily living (ADL). Objectives: In this pilot study, home-based physical behavior was assessed to examine whether it is possible to distinguish mild cognitive impairment (PD-MCI) from PDD. Methods: Fifty-five patients with mild to severe Parkinson disease (PD) participated in this cross-sectional study. Based on comprehensive neuropsychological testing, PD patients were classified as cognitively nonimpaired (PD-NC), PD-MCI or PDD. For physical behavior assessments, patients wore the accelerometer DynaPort® (McRoberts) for 3 days. Ordinal logistic regression models with continuous Y were applied to correct results for motor impairment and depressive symptoms. Results: After excluding 7 patients due to insufficient wearing time, 48 patients with a mean of 2 recorded days were analyzed (17 PD-NC, 22 PD-MCI, 9 PDD). ADL-impaired PDD patients showed fewer sedentary bouts than non-ADL-impaired PD-MCI (p = 0.01, odds ratio [OR] = 8.9, 95% confidence interval [CI] = 1.8-45.2) and PD-NC (p = 0.01, OR = 10.3, CI = 1.6-67.3) patients, as well as a longer sedentary bout length (PD-NC: p = 0.02, OR = 0.1, CI = 0.02-0.65; PD-MCI: p = 0.02, OR = 0.14, CI = 0.03-0.69). These differences were mainly caused by fewer (PD-NC: p = 0.02, OR = 9.6, CI = 1.5-62.4; PD-MCI: p = 0.01, OR = 8.5, CI = 1.5-37.3) but longer sitting bouts (PD-NC: p = 0.03, OR = 0.12, CI = 0.02-0.80; PD-MCI: p = 0.04, OR = 0.19, CI = 0.04-0.93). Tests assessing executive function, visuoconstruction and attention correlated significantly with specific activity parameters (ρ ≥ 0.3; p < 0.05). Conclusion: Objective assessment of physical behavior, in particular the detection of sedentary bouts, is a promising contributor to the discrimination between PD-MCI and PDD.