S. F. Cappa

Classification of primary progressive aphasia and its variants

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.

The logopenic/phonological variant of primary progressive aphasia

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.

Different neural systems for the recognition of animals and man-made tools

Using positron emission tomography, we mapped brain activity in normal volunteers during the recognition of visual stimuli representing living (animals) and nonliving (artefacts) entities. The subjects had to decide whether pairs of visual stimuli were different representations of the same object, or different objects. Animal recognition was associated with activations in the inferior temporo-occipital areas, bilaterally, whereas artefact recognition engaged a predominantly left hemispheric network, involving the left dorsolateral frontal cortex. These findings, which concur with clinical observations in neurological patients, provide in vivo evidence for a fractionation of the neural substrates of semantic knowledge in man.

Executive dysfunction in early Alzheimer's disease.

Twenty five patients with probable mild Alzheimers disease were assessed for deficits in executive functioning and the impact of these deficits on performance in other neuropsychological domains. The Wisconsin card sorting test, the release from proactive interference paradigm, the verbal fluency test, and the Stroop test were adopted to classify patients with (AD+) and without (AD-) executive deficits. Seven of the patients showed an impairment in executive function (AD+), defined as a performance below the cut off score in at least two of these tests. There were no significant differences in clinical assessments, demographic features, or other cognitive functions between patients. Executive dysfunction may be an early additional feature in a subgroup of patients with mild Alzheimers disease. Impairment on frontal lobe tests does not seem to be related to the severity or duration of disease, or to a different pattern of impairment in other cognitive domains.

Neuropsychological assessment in idiopathic REM sleep behavior disorder (RBD): Does the idiopathic form of RBD really exist?

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.

Education and occupation as proxies for reserve in aMCI converters and AD FDG-PET evidence

Background: Previous reports have shown that higher education is associated with more severe brain pathology in patients with Alzheimer disease (AD), suggesting that these individuals have a functional reserve provided by education, which masks the clinical expression of a higher degree of neurodegeneration. It is unknown if a similar reserve mechanism exists in patients with amnestic mild cognitive impairment (aMCI). The aim of this study was to assess the impact of education and occupation on brain glucose metabolism (rCMRglc) measured with FDG-PET in aMCI and in a very large sample of subjects with probable AD (pAD). Methods: A total of 242 patients with pAD, 72 with aMCI, and 144 healthy controls participated in the study. At follow-up, 21 subjects with aMCI progressed to AD. A regression analysis was conducted (SPM2), with education and occupation as independent variables, and rCMRglc as dependent variable, adjusting for demographic data, global cognitive status, and neuropsychological scores. Results: The analysis showed a significant association between higher education/occupation and lower rCMRglc in posterior temporoparietal cortex and precuneus in pAD and aMCI converters, and no correlation in aMCI nonconverters and healthy controls. This means that, when submitted to FDG-PET for diagnostic evaluation, pAD and aMCI converters with higher education/occupation had, for comparable cognitive impairment, a more severe rCMRglc reduction than the ones with lower education/occupation. Conclusions: This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer disease (AD) pathology. The results in aMCI converters suggest that functional reserve is already at play in the predementia phase of AD.

The role of the left frontal lobe in action naming rTMS evidence

BackgroundNeuropsychological and neuroimaging studies suggest that whereas the left temporal neocortex plays a crucial role in all tasks involving lexical–semantic processing, some regions of the left prefrontal convexity are selectively recruited during verb processing. ObjectiveTo determine if there are different neural correlates for noun and verb processing in the human brain. MethodsRepetitive transcranial magnetic stimulation (rTMS), 20 Hz at 90% of the motor threshold, was applied to left or right prefrontal brain during object- and action-naming tasks in nine healthy subjects. ResultsA shortening of naming latency for actions was observed only after stimulation of left prefrontal cortex. ConclusionThe involvement of the left dorsolateral frontal cortex in action naming was demonstrated using rTMS.

Action and object naming in frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration.

Action naming has been reported to be disproportionately impaired in comparison to object naming in patients with frontotemporal dementia (FTD). This finding has been attributed to the crucial role of frontal cortex in action naming. The investigation of object and action naming in the different subtypes of FTD, as well as in the related conditions of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), may thus contribute to the elucidation of the cerebral correlates of the action-object discrepancy as well as provide clues to the underlying cognitive mechanisms. The results indicated that, with the exception of semantic dementia, action naming was more impaired than object naming in all patient groups. The discrepancy was similar in frontal variant of FTD and Alzheimers disease patients, whereas patients with nonfluent primary progressive aphasia, PSP, and CBD were significantly more impaired in the oral production of actions than of objects. These findings indicate that action naming impairment is not a general feature of FTD, but rather is associated with conditions that affect the frontoparietal-subcortical circuits involved in action knowledge and action representation.

Neuropsychological assessment in patients with relapsing-remitting multiple sclerosis and mild functional impairment: correlation with magnetic resonance imaging.

Forty one moderately impaired patients with clinically confirmed multiple sclerosis (MS) and a relapsing-remitting course were submitted to a neuropsychological battery and magnetic resonance imaging (MRI) to correlate the neuropsychological performances with the degree of cerebral demyelination. The neuropsychological results were indicative of a very mild overall impairment. The patients were subdivided into two groups (extensive periventricular demyelination or discrete lesions on MRI) and the results of neuropsychological tests compared. Patients with extensive periventricular demyelination had an inferior performance on concept formation, non-verbal reasoning and verbal memory tests.

Education and occupation provide reserve in both ApoE ε4 carrier and noncarrier patients with probable Alzheimer’s disease

According to the reserve hypothesis, a high educational/occupational attainment can modulate Alzheimer’s disease (AD) clinical expression. The impact of the Apolipoprotein E (ApoE) ε4 allele on the reserve mechanism in AD has not been assessed. Aim of this European multicenter study was to evaluate the metabolic correlates of reserve and ApoE genotype in early probable AD. 51 AD subjects, 27 ε4 carriers, and 24 noncarriers, underwent FDG-PET brain imaging. We used the general linear model as implemented in SPM2 to test for the linear correlation of a reserve index, accounting for both educational and occupational level, with brain glucose metabolism, controlling for demographic variables (age and gender) and for cognitive performance. We found an inverse correlation between a reserve index, accounting for educational/occupational level, and metabolism in the posterior cingulate cortex and precuneus in both ε4 carriers and noncarriers, and no significant difference between the groups. We show that education and occupation act as proxies for reserve in ε4 carriers, compensating for an unfavorable genetic background; we also show that the degree of compensation does not differ significantly by ApoE ε4 status.