) for a scientific commentary on this article.A GGGGCC repeat expansion in C9orf72 leads to frontotemporal dementia and/or amyotrophic lateral sclerosis. Diverse pathological features have been identified, and their disease relevance remains much debated. Here, we describe two illuminating patients with frontotemporal dementia due to the C9orf72 repeat expansion. Case 1 was a 65-year-old female with behavioural variant frontotemporal dementia accompanied by focal degeneration in subgenual anterior cingulate cortex, amygdala, and medial pulvinar thalamus. At autopsy, widespread RNA foci and dipeptide repeat protein inclusions were observed, but TDP-43 pathology was nearly absent, even in degenerating brain regions. Case 2 was a 74-year-old female with atypical frontotemporal dementia-motor neuron disease who underwent temporal lobe resection for epilepsy 5 years prior to her first frontotemporal dementia symptoms. Archival surgical resection tissue contained RNA foci, dipeptide repeat protein inclusions, and loss of nuclear TDP-43 but no TDP-43 inclusions despite florid TDP-43 inclusions at autopsy 8 years after first symptoms. These findings suggest that C9orf72-specific phenomena may impact brain structure and function and emerge before first symptoms and TDP-43 aggregation. Keywords: frontotemporal dementia; protein aggregation; TDP-43 Abbreviations: ALS = amyotrophic lateral sclerosis; FTD = frontotemporal dementia; mPULV = medial pulvinar nucleus of the thalamus; NCI = neuronal cytoplasmic inclusion

The Neuropsychiatric Inventory (NPI) is a standardized, validated, and reliable tool to assess neuropsychiatric derangements in dementia patients. The aim of this study is to develop the Korean version of the NPI (K-NPI) and to test its reliability and usefulness in dementia patients. The subjects were 49 normal controls and 92 patients with Alzheimer's disease (43), vascular dementia (32), frontotemporal lobar degeneration (11), and other causes (6). Their caregivers familiar with the subjects' everyday behavior were interviewed with the K-NPI. In a subgroup (29/141) of the caregivers, the K-NPI was repeated for test-retest reliability, average of 23.1 days after the initial test. Prevalence rates of 12 behavioral domains in dementia patients were comparable to those of the original NPI; apathy was the most common and hallucination was the least common behavior. Total K-NPI scores correlated positively with dementia severity assessed with the Korean Mini-Mental State Examination. Test-retest reliabilities of frequencies and severities of all subscales were significantly high. Depression, anxiety, apathy, irritability, night-time behavior, and eating change were identified at very low rates in normal controls and were significantly less than those in dementia patients (p<0.001). The K-NPI, whose reliability and competency are comparable to those of the original version, may be a reliable and useful tool for measuring neuropsychiatric disturbances in Korean dementia patients.

Family caregivers of terminal cancer patients experience burdens, but caregiving also has positive consequences. This study has important implications for the development of bereavement interventions that aim to encourage positive outcomes and reduce negative outcomes for caregivers.

The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies.OBJECTIVE To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). DESIGN, SETTING, AND PARTICIPANTSThis prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. MAIN OUTCOMES AND MEASURESClinical, cognitive, neuroimaging, and pathology results. RESULTS Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. CONCLUSIONS AND RELEVANCE Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.