The Cerebellum Is a Key Structure in the Neural Network for Mentalizing: An MRI Study in the Behavioral Variant of Frontotemporal Dementia.

The behavioural variant of frontotemporal dementia (bvFTD) is primarily characterized by deficits in social behaviour and theory of mind (ToM). Although a consensus has been reached on the roles of the cerebellum in social cognition and ToM, its specific contribution to social impairments of bvFTD has never been specifically investigated. The aim of this study was to assess cerebellar structural and functional changes in patients with bvFTD and their potential association with ToM deficits of patients. Therefore, 15 patients with bvFTD and 34 healthy subjects underwent an MRI examination. Voxel-based morphometry was used to assess cerebellar (GM) changes, and a seed-based analysis was performed to test cerebello-cerebral functional connectivity (FC). The performance of bvFTD patients in a ToM task was then correlated with FC patterns. Compared to healthy subjects, patients with bvFTD showed significant cerebellar GM loss specifically involving cerebellar Crus I-II. Additionally, FC changes FC were observed between the cerebellum and cerebral regions related to ToM. Interestingly, patterns of changes in cerebello-cerebral FC correlated with altered ToM performances explored using the "Reading the Mind with the Eyes" test (RMET) of patients. The present findings suggest that specific changes in cerebello-cerebral FC may underlie ToM alterations in patients with bvFTD.

Semantic Memory as an Early Cognitive Marker of Alzheimer's Disease: Role of Category and Phonological Verbal Fluency Tasks.

BACKGROUND: The assessment of semantic memory may be a useful marker to identify individuals with mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD) in the early stages of the disease. OBJECTIVE: The aim of this five-year follow-up longitudinal study is to assess whether semantic assessment could predict progression in MCI. METHODS: A population of MCI (N = 251); mild (N = 178) and moderate AD (N = 114); and a sample of healthy participants (HP; N = 262) was investigated. The five-year follow-up of the MCI group was completed by 178 patients. Semantic and episodic memory measures were used, including a measure of the discrepancy between categorical and phonological verbal fluency, the semantic-phonological delta (SPD). The main outcome was the progression of MCI due to AD to dementia. RESULTS: A general linear model showed a significant effect of diagnosis on SPD (Wilks' Lambda = 0.591; p < 0.001). The estimated marginal means were -0.91 (SE = 0.185) in HP, -1.83 (SE = 0.187) in MCI, -1.16 (SE = 0.218) in mild AD, and -1.02 (SE = 0.275) in moderate AD. Post-hoc comparisons showed a significant difference between MCI and HP (p < 0.001). The follow-up was completed by 178 MCI individuals. SPD in MCI patients who progress to dementia was significantly lower than in MCI that will not progress (p = 0.003). Together with the Mini-Mental State Examination, the SPD was the only measure with a significant predicting effect at the five-years follow-up (p = 0.016). CONCLUSION: The SPD indicates the impairment of semantic memory in individuals with underlying AD at the MCI early stage, reflecting the early involvement of perirhinal and entorhinal cortices in the earliest stages of AD neuropathological process.

Semantic Relations in a Categorical Verbal Fluency Test: An Exploratory Investigation in Mild Cognitive Impairment.

Categorical verbal fluency tests (CFT) are commonly used to assess the integrity of semantic memory in individuals with brain damage. Persons with Dementia of the Alzheimer's Type display a reduced output on CFT, and a similar pattern has been reported in persons with amnesic Mild Cognitive Impairment (aMCI). The aims of the present study were to assess whether the semantic relations between lexical entries produced on a categorical fluency test were different between healthy persons and those with aMCI, and whether this difference was more pronounced in individuals who converted to dementia during a 3-year follow-up period. METHODS: We recruited 34 individuals with aMCI and 29 matched healthy persons. During the follow-up period, 10 individuals converted to Dementia (aMCI-conv). Two measures assessing semantic relations between consecutively produced word pairs (Path length and Extended Gloss Overlap) were obtained from the Wordnet database. RESULTS: The number of word pairs analyzed among the healthy participants (HP) and persons with aMCI were 498 (birds: 262; pieces of furniture: 236) and 395 (birds: 174; pieces of furniture: 221), respectively. Path length was lower in aMCI-conv than in HP (p = 0.035), but no differences were found between stable aMCI and HP, and between aMCI-stable and aMCI-conv. The ANOVA for lexical entries belonging to the "birds" category showed a significant effect of group (F = 5.630; p = 0.004); the post hoc analysis showed a significant difference between HP and aMCI-conv (p = 0.003). The "pieces of furniture" category was significantly affected by group (F = 4.107; p = 0.017); the post hoc test showed significant differences between aMCI-conv and healthy individuals (p = 0.049), and between aMCI-conv and stable aMCI (p = 0.001). DISCUSSION: Individuals with aMCI who convert to dementia show a deterioration in the semantic relations between lexical entries, produced on a CFT. This phenomenon may be interpreted as a marker of a very early disruption of semantic memory.

Standardization, Clinical Validation, and Typicality Norms of a New Test Assessing Semantic Verbal Fluency.

OBJECTIVE: Semantic verbal fluency (SVF) tests are widely used in clinical neuropsychology. We propose the standardization and clinical validation of a new SVF test based on the production of names of birds and articles of furniture (Birds and Articles of Furniture test-BAF). METHODS: A sample of 268 subjects aged 40 years or more underwent the test. The clinical validation was conducted on subjects affected by amnesic Mild Cognitive Impairment (aMCI; N = 106), mild (N = 178), and moderate (N = 114) Alzheimer's disease (AD). RESULTS: The BAF total score was influenced by both age and education, whereas the single scores obtained on BAF were also influenced by gender. The percentage of subjects with pathological score on BAF increased from aMCI (19%) to mild (45.5%) and moderate (71.1%) AD, and receiver operating characteristic curves analysis showed that the BAF may be highly reliable in distinguishing aMCI and AD patients from healthy subjects. We also provide typicality norms for birds and articles of furniture that could be useful in the assessment of qualitative features of words produced in semantic fluency tests. CONCLUSIONS: The BAF test could be a valid and reliable tool in both clinical practice and research on subjects affected by cognitive impairment.

Typicality of words produced on a semantic fluency task in amnesic mild cognitive impairment: linguistic analysis and risk of conversion to dementia.

Semantic and, to a lesser extent, phonological verbal fluency tasks are impaired in Alzheimer's disease (AD) and in amnesic mild cognitive impairment (aMCI). Furthermore, both fluency tasks have been considered as possible markers of conversion from aMCI to AD. Up to recent years, the use of fluency tasks has been limited to word count, but, more recently, linguistic variables, such as word frequency, age of acquisition, familiarity, and typicality, have also been considered. In particular, attention has been focused on typicality of words produced on semantic verbal fluency tasks, because the tendency to produce only the more typical members of various categories points to an impoverishment of semantic memory. The aim of our study was to compare in aMCI, AD, and control subjects a lexical (word frequency) and a lexical-semantic variable (item typicality) in a semantic verbal fluency task, and to evaluate the possible value of these variables in predicting conversion from aMCI to AD during a 2 years follow-up period. We found no difference in mean typicality of words produced by aMCI and AD subjects whereas both groups produced words of higher mean typicality than control subjects. Furthermore, to assess the relationship between typicality values and risk of conversion to AD, the aMCI group was split in two subgroups, including subjects who obtained a mean typicality value lower or higher than the median value of the whole aMCI group. Consistent with our hypothesis, conversion to AD was significantly more frequent in high typicality than in low typicality subjects.