Objective To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease (ND). Method Systematic, retrospective, blinded chart review of patients with a ND diagnosis [behavioral variant frontotemporal dementia (bvFTD n=69); Alzheimer’s disease (AD n=65); semantic dementia (SemD n=41); progressive non-fluent aphasia (PNFA n=17); corticobasal degeneration (n=25); progressive supranuclear palsy (n=15); and amyotrophic lateral sclerosis (ALS n=20)]. Results 28.2% of patients with a ND received a prior psychiatric diagnosis. Depression was the most common psychiatric diagnosis in all groups. BvFTD patients received a prior psychiatric diagnosis significantly more often (52.2%) than patients with AD (23.1%), SemD (24.4%), or PNFA (11.8%), and were more likely to receive diagnoses of bipolar affective disorder or schizophrenia than patients with other NDs (p<0.001). Younger age, higher education and a family history of psychiatric illness increased the rate of prior psychiatric diagnosis in patients with bvFTD (p<0.05). Cognitive, behavioral and emotional characteristics did not distinguish patients who did and did not receive a prior psychiatric diagnosis. Conclusion ND is often mistaken for psychiatric disease with bvFTD patients at highest risk for misdiagnosis. Because psychiatric misdiagnosis can lead to delayed and inappropriate treatment, and family and patient distress, physicians should consider referring mid- to late-life patients with new onset neuropsychiatric symptoms for ND evaluation.

Objective: To describe the phenotype of patients with C9FTD/ALS (C9ORF72) hexanucleotide repeat expansion. Methods:A total of 648 patients with frontotemporal dementia (FTD)-related clinical diagnoses and Alzheimer disease (AD) dementia were tested for C9ORF72 expansion and 31 carried expanded repeats (C9ϩ Results: All C9ϩ patients displayed clinical syndromes of bvFTD, ALS, or FTD-MND. At first evaluation, C9ϩ bvFTD patients had more delusions and greater impairment of working memory, but milder eating dysregulation compared to bvFTD noncarriers. C9ϩFTD-MND patients had a trend for longer survival and had an earlier age at onset than FTD-MND noncarriers. Voxel-based morphometry demonstrated more thalamic atrophy in FTD and FTD-MND carriers than in noncarriers. Conclusions: GLOSSARYAD ϭ Alzheimer disease; ALS ϭ amyotrophic lateral sclerosis; bvFTD ϭ behavioral variant frontotemporal dementia; CBS ϭ corticobasal syndrome; CDR-SB ϭ Clinical Dementia Rating Scale sum of boxes; FTD ϭ frontotemporal dementia; FWE ϭ familywise error; glm ϭ generalized linear model; lvPPA ϭ logopenic variant primary progressive aphasia; MND ϭ motor neuron disease; nfvPPA ϭ nonfluent variant primary progressive aphasia; NPI ϭ Neuropsychiatric Inventory; PSP ϭ progressive supranuclear palsy; svPPA ϭ semantic variant primary progressive aphasia; UCSF ϭ University of California, San Francisco; VBM ϭ voxel-based morphometry.Frontotemporal dementia (FTD) is a common dementia syndrome among patients presenting before 65 years of age with prevalence equal to Alzheimer disease (AD) dementia.1,2 FTD often overlaps with amyotrophic lateral sclerosis (ALS), with symptoms of FTD occurring in 15%-41% of patients with ALS and features of ALS occurring in 15% of FTD.3,4 Many patients with FTD and ALS exhibit autosomal dominant family histories (FTD 10% 5 ; ALS 5%-10% 6 ; FTD-motor neuron disease [MND] 37% 7 ) and a number of large familial cohorts have been linked to a chromosome 9p region. [7][8][9][10][11][12] Recently, a noncoding expanded hexanucleotide repeat in chromosome 9 open reading frame 72 (C9ORF72) was identified as the cause of chromosome 9p-associated FTD and ALS. 13,14 This mutation is the most common genetic cause of familial and sporadic behavioral variant FTD (bvFTD) and ALS.In one study, the C9ORF72 (C9FTD/ALS) expansion accounted for 11.7% of familial FTD, 22.5% of familial ALS, and 4% of sporadic ALS.13 Previous family studies of chromosome 9p-linked families 7,8,10 suggested that some features may distinguish this mutation from sporadic