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The logopenic variant of primary progressive aphasia (lvPPA) is the most recent variant of primary progressive aphasia (PPA) to be identified; thus far, it has been poorly investigated. Despite being typically associated with Alzheimer disease (AD), lvPPA has recently been linked to frontotemporal lobe degeneration (FTLD), with distinctive cognitive and neural features that are worthy of further investigation. Here, we describe the neuropsychological and linguistic profile, as well as cerebral abnormalities, of an individual exhibiting PPA and carrying a pathogenetic variant in the GRN gene, from a 3-year longitudinal perspective. The individual's initial profile resembled lvPPA because it was characterized by word-finding difficulties and phonological errors in spontaneous speech in addition to sentence repetition and phonological short-term memory impairments. The individual's structural and metabolic imaging data demonstrated left temporal and bilateral frontal atrophy and hypometabolism, respectively. On follow-up, as the pathology progressed, dysprosody, stereotypical speech patterns, agrammatism, and orofacial apraxia appeared, suggesting an overlap with the nonfluent variant of PPA (nfvPPA). Severe sentence comprehension impairment also became evident. Our longitudinal and multidisciplinary diagnostic approach allowed us to better characterize the progression of a GRN-positive lvPPA profile, providing neuropsychological and imaging indicators that might be helpful to improve classification between different PPA variants and to address a nosological issue. Finally, we discuss the importance of early diagnosis of PPA given the possible overlap between different PPA variants during the progression of the pathology.

Objective: Revised research criteria for the diagnosis of Alzheimer disease have been proposed to capture patients presenting with mild and not yet disabling symptoms, and currently classified as mild cognitive impairment (MCI). We describe 2 very mild cases of MCI and their clinical outcome. Methods: The 2 cases were selected as they had unequivocal preservation of daily activities and normal global cognitive performance (Mini-Mental State Examination 29/30) and were positive to all 3 markers. Cognitive profile was assessed with an extensive neuropsychologic battery, medial temporal atrophy with hippocampal volumetry, hypometabolism on 18 F-deoxyglucose positron emission tomography and voxel-based statistical parametric mapping analysis, and tau and amyloid beta-42 in the cerebrospinal fluid with enzyme-linked immunosorbent assay. Results: Both patients had a poor performance in 2 out of 11 neuropsychologic tests. Both had hippocampal volumes at or below the first percentile of the age-specific distribution, retrosplenial glucose hypometabolism, and inversion of tau/amyloid beta-42 cerebrospinal fluid ratio. Both showed progression of the cognitive deficit over the following 12 months. Conclusions: These 2 patients with progressive MCI and positivity to all Alzheimer markers predicated by the new research criteria provide preliminary support to their validity. Future work will characterize the marker profile of the vast majority of patients with incomplete marker positivity.

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. GLOSSARY: AD = Alzheimer disease; BA = Brodmann area; CDR = Clinical Dementia Rating; CVLT-MS = California Verbal Learning Test–Mental Status Edition; ECD = ethyl cysteinate dimer; FWHM = full-width at half-maximum; GM = gray matter; LPA = logopenic progressive aphasia; MMSE = Mini-Mental State Examination; PNFA = progressive nonfluent aphasia; PPA = primary progressive aphasia; Rey-O = Rey–Osterrieth; SemD = semantic dementia; VBM = voxel-based morphometry; WAB = Western Aphasia Battery; WAIS-III = Wechsler Adult Intelligence Scale, Third Edition.

We read with interest the report by Romito et al. about a patient with fixed dystonia who responded to motor cortex stimulation.1 In our view, their conclusions are limited by uncertainties about the diagnosis and shortcomings in the evaluation of the therapeutic response. These aspects are important when an invasive neurosurgical procedure is proposed for consideration in similar cases. The diagnosis of psychogenic dystonia is excluded by the authors with the statement that “nothing indicated somatoform or psychogenic disorder.”1 This diagnosis should be suspected when patients have fixed and painful posturing of the neck or limbs, which renders them unable to carry out basic daily activities.2 Possible, probable, documented, and clinically established categories of certainty can be established by applying Fahn and Williams' criteria.3 Only 10% of the fixed dystonia cohort evaluated prospectively with a standardized neuropsychiatric protocol by Schrag et al. did not meet criteria for psychogenic dystonia.4 Furthermore, the posture exhibited by this patient is similar to …