Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system. Patients with FTLD were distributed between FTLD-tau (34 patients: 10 corticobasal degeneration, nine progressive supranuclear palsy, eight Pick's disease, three frontotemporal dementia with parkinsonism associated with chromosome 17, three unclassifiable tauopathy, and one argyrophilic grain disease); FTLD-TDP (55 patients: nine type A including one with motor neuron disease, 27 type B including 21 with motor neuron disease, eight type C with right temporal lobe presentations, and 11 unclassifiable including eight with motor neuron disease), FTLD-FUS (eight patients), and one patient with FTLD-ubiquitin proteasome system positive inclusions (FTLD-UPS) that stained negatively for tau, TDP-43, and FUS. Alzheimer's disease was uncommon (6%) among patients whose only top diagnosis during follow-up was bvFTD. Seventy-nine per cent of FTLD-tau, 86% of FTLD-TDP, and 88% of FTLD-FUS met at least 'possible' bvFTD diagnostic criteria at first presentation. The frequency of the six core bvFTD diagnostic features was similar in FTLD-tau and FTLD-TDP, suggesting that these features alone cannot be used to separate patients by major molecular class. Voxel-based morphometry revealed that nearly all pathological subgroups and even individual patients share atrophy in anterior cingulate, frontoinsula, striatum, and amygdala, indicating that degeneration of these regions is intimately linked to the behavioural syndrome produced by these diverse aetiologies. In addition to these unifying features, symptom profiles also differed among pathological subtypes, suggesting distinct anatomical vulnerabilities and informing a clinician's prediction of pathological diagnosis. Data-driven classification into one of the 10 most common pathological diagnoses was most accurate (up to 60.2%) when using a combination of known predictive factors (genetic mutations, motor features, or striking atrophy patterns) and the results of a discriminant function analysis that incorporated clinical, neuroimaging, and neuropsychological data.
Recent functional neuroimaging studies implicate the network of mesolimbic structures known to be active in reward processing as the neural substrate of pleasure associated with listening to music. Psychoacoustic and lesion studies suggest that there is a widely distributed cortical network involved in processing discreet musical variables. Here we present the case of a young man with auditory agnosia as the consequence of cortical neurodegeneration who continues to experience pleasure when exposed to music. In a series of musical tasks the subject was unable to accurately identify any of the perceptual components of music beyond simple pitch discrimination, including musical variables know to impact the perception of affect. The subject subsequently misidentified the musical character of personally familiar tunes presented experimentally, but continued to report the activity of "listening" to specific musical genres was an emotionally rewarding experience. The implications of this case for the evolving understanding of music perception, music misperception, music memory, and music-associated emotion are discussed.
We present longitudinal clinical, cognitive and neuroimaging data from a 63-year-old woman who enrolled in research as a normal control and evolved posterior cortical atrophy (PCA) over five year follow-up. At baseline she reported only subtle difficulty driving and performed normally on cognitive tests, but already demonstrated atrophy in left visual association cortex. With follow-up she developed insidiously progressive visuospatial and visuoperceptual deficits, correlating with progressive atrophy in bilateral visual areas. Amyloid PET was positive. This case tracks the evolution of PCA from the prodromal stage, and illustrates challenges to early diagnosis as well as the utility of imaging biomarkers.
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