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Objective: To characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers., Methods: Participants included patients with a mutation in MAPT , PGRN , or C9orf72 , or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers., Results: A total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings., Conclusions: Ventricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA--nonfluent/agrammatic, semantic, and logopenic--were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as "imaging-supported" if the expected pattern of atrophy is found and "with definite pathology" if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.

Objective: Primary progressive aphasia (PPA) is characterized by isolated decline in language functions. Semantic dementia and progressive nonfluent aphasia are accepted PPA variants. A "logopenic" variant (LPA) has also been proposed, but its cognitive and anatomic profile is less defined. The aim of this study was to establish the cognitive and anatomic features of LPA., Methods: Six previously unreported LPA cases underwent extensive neuropsychological evaluation and an experimental study of phonological loop functions, including auditory and visual span tasks with digits, letters, and words. For each patient, a voxel-wise, automated analysis of MRI or SPECT data were conducted using SPM2., Results: In LPA, speech rate was slow, with long word-finding pauses. Grammar and articulation were preserved, although phonological paraphasias could be present. Repetition and comprehension were impaired for sentences but preserved for single words, and naming was moderately affected. Investigation of phonological loop functions showed that patients were severely impaired in digit, letter, and word span tasks. Performance did not improve with pointing, was influenced by word length, and did not show the normal phonological similarity effect. Atrophy or decreased blood flow was consistently found in the posterior portion of the left superior and middle temporal gyri and inferior parietal lobule., Conclusions: Logopenic progressive aphasia (LPA) is a distinctive variant of primary progressive aphasia. Cognitive and neuroimaging data indicate that a deficit in phonological loop functions may be the core mechanism underlying the LPA clinical syndrome. Recent studies suggest that Alzheimer disease may be the most common pathology underlying the LPA clinical syndrome.

Objective: To evaluate the cognitive performance of patients with idiopathic REM sleep behavior disorder (RBD)., Methods: The authors studied 17 consecutive patients with idiopathic RBD vs 17 age- and education-matched control subjects. Tests given to each patient and control included Mini-Mental State Examination, verbal and spatial short-term memory, visual selective attention, verbal fluency, prose memory, visuoconstructional abilities, spatial learning, and executive function tests. A self-administered depression rating scale was also used., Results: RBD patients had significantly lower scores than control subjects in two tests: copy of Rey-Osterrieth Figure and Corsi Supraspan Learning. No correlation was found between the results of neuropsychological tests and RBD duration or with polysomnographic findings., Conclusions: Visuospatial constructional dysfunction and altered visuospatial learning may be present in idiopathic RBD. A neuropsychological assessment may be indicated in RBD patients.

Objective: To compare brain involvement in myotonic dystrophy (DM) with that of proximal myotonic myopathy (PROMM)., Background: PROMM is a multisystem disease with many features in common with DM., Methods: Twenty patients with DM (CTGF[500-700), 20 patients with PROMM, and 20 normal control subjects were studied. Neuropsychological testing was performed in 12 patients with PROMM and in 18 patients with DM; brain MRI was performed in 17 of 20 PROMM patients and 15 of 20 DM patients. Ten patients with PROMM and 11 patients with DM were subjected to H2(15)O PET., Results: Two-thirds of the patients with PROMM and one-half of those with DM were impaired on visual-spatial recall, whereas one-third of the patients with PROMM and less than half of those with DM showed an impairment in visual-spatial construction. Brain MRI was normal, or showed only nonspecific white matter abnormalities in both PROMM and DM patients. PET studies in PROMM patients showed a bilateral decrease in regional cerebral blood flow (rCBF) of the orbitofrontal and medial frontal cortex, whereas DM patients had more widespread hypoperfusion that extended to the dorsolateral frontal cortex and subcortical regions., Conclusions: Impaired visual-spatial function may be present in proximal myotonic myopathy. This correlates best with a reduction in regional cerebral blood flow observed in H2(15)O PET brain scans rather than with specific structural abnormalities observed on brain MRI.

To assess noun and verb processing in different dementia types, we tested object and action naming in three groups of subjects: probable Alzheimer's disease (AD) with mild to moderate dementia; age- and education-matched normal subjects; and a group of frontotemporal dementia (FTD) patients. AD and FTD patients were impaired in naming compared with control subjects; action naming was more severely impaired. However, the discrepancy between object and action naming was significantly greater in FTD than in AD patients, independent of the severity of dementia or of overall language impairment. The latter finding is compatible with the hypothesis that the frontal lobe plays a crucial role in action naming. A relatively selective impairment in action naming might be a characteristic neuropsychological feature of FTD.

Using functional magnetic resonance imaging (fMRI), we mapped brain activity in six normal volunteers during two silent verbal fluency tasks, one with a phonemic (letter) cue and one with a semantic (category) cue. In comparison with resting state, both tasks activated the anterior triangular portion of the left inferior frontal gyrus (IFG or F3, for third frontal gyrus) and the left thalamus. There were also areas activated in one task but not in the other: the posterior opercular portion of the left IFG for phonemic fluency, and the left retrosplenial region for semantic fluency. Our findings concur with normal psychophysical data and neuropsychological observations to suggest the recruitment of two overlapping but dissociable systems for the two tasks, and demonstrate functional heterogeneity within the left IFG (Broca's area), where the opercular portion is responsible for obtaining access to words through a phonemic/articulatory route.

We used positron emission tomography to study brain activity in adults while they were listening to stories in their native language, in a second language acquired after the age of seven, and in a third unknown language. Several areas, similar to those previously observed in monolinguals, were activated by the native but not by the second language. Both the second and the unknown language yielded distinct left-hemispheric activations in areas specialized for phonological processing, which were not engaged by a backward speech control task. These results indicate that some brain areas are shaped by early exposure to the maternal language, and are not necessarily activated by the processing of a second language to which they have been exposed for a limited time later in life.