Katia Fabi

Short-term memory binding is impaired in AD but not in non-AD dementias.

Binding is a cognitive function responsible for integrating features within complex stimuli (e.g., shape-colour conjunctions) or events within complex memories (e.g., face-name associations). This function operates both in short-term memory (STM) and in long-term memory (LTM) and is severely affected by Alzheimers disease (AD). However, forming conjunctions in STM is the only binding function which is not affected by healthy ageing or chronic depression. Whether this specificity holds true across other non-AD dementias is as yet unknown. The present study investigated STM conjunctive binding in a sample of AD patients and patients with other non-AD dementias using a task which has proved sensitive to the effects of AD. The STM task assesses the free recall of objects, colours, and the bindings of objects and colours. Patients with AD, frontotemporal dementia, vascular dementia, lewy body dementia and dementia associated with Parkinsons disease showed memory, visuo-spatial, executive and attentional deficits on standard neuropsychological assessment. However, only AD patients showed STM binding deficits. This deficit was observed even when memory for single features was at a similar level across patient groups. Regression and discriminant analyses confirmed that the STM binding task accounted for the largest proportion of variance between AD and non-AD groups and held the greatest classification power to identify patients with AD. STM conjunctive binding places little demands on executive functions and appears to be subserved by components of the memory network which are targeted by AD, but not by non-AD dementias.

Foreign accent syndrome as the initial sign of primary progressive aphasia

Foreign accent syndrome (FAS) is a rare speech disorder characterised by the emergence of a new accent, perceived by listeners as foreign. FAS has usually been described following focal brain insults, such as stroke. We describe the unusual case of a woman presenting with FAS as the earliest symptom of progressive degenerative brain disease. At presentation, she showed no language or other cognitive impairment, and functional and structural brain imaging were normal. Follow-up 1 year later revealed the emergence of mild expressive language problems. Repeat functional neuroimaging showed mild hypoperfusion of the perisylvian speech area of the left hemisphere, and structural imaging showed mild left perisylvian atrophy. We interpret the case as an unusual presentation of primary progressive non-fluent aphasia. The case provides further evidence of the variable and circumscribed nature of the clinical presentation of focal cerebral degeneration.

Relational and conjunctive binding functions dissociate in short-term memory

Remembering complex events requires binding features within unified objects (conjunctions) and holding associations between objects (relations). Recent studies suggest that the two functions dissociate in long-term memory (LTM). Less is known about their functional organization in short-term memory (STM). The present study investigated this issue in patient AE affected by a stroke which caused damage to brain regions known to be relevant for relational functions both in LTM and in STM (i.e., the hippocampus). The assessment involved a battery of standard neuropsychological tasks and STM binding tasks. One STM binding task (Experiment 1) presented common objects and common colors forming either pairs (relations) or integrated objects (conjunctions). Free recall of relations or conjunctions was assessed. A second STM binding task used random polygons and non-primary colors instead (Experiment 2). Memory was assessed by selecting the features that made up the relations or the conjunctions from a set of single polygons and a set of single colors. The neuropsychological assessment revealed impaired delayed memory in AE. AE’s pronounced relational STM binding deficits contrasted with his completely preserved conjunctive binding functions in both Experiments 1 and 2. Only 2.35% and 1.14% of the population were expected to have a discrepancy more extreme than that presented by AE in Experiments 1 and 2, respectively. Processing relations and conjunctions of very elementary nonspatial features in STM led to dissociating performances in AE. These findings may inform current theories of memory decline such as those linked to cognitive aging.

Applause sign: is it really specific for Parkinsonian disorders? Evidence from cortical dementias

Objective The applause sign, originally reported as a specific sign of progressive supranuclear palsy (PSP), has recently been found in several parkinsonian disorders. Its nature is still uncertain. It has been interpreted as a motor perseveration or a form of apraxia. The present study aims to: (a) verify the specificity of the applause sign for parkinsonian disorders, examining the presence of the applause sign in cortical dementias which should be error free and (b) clarify the nature of the applause sign (resulting or not from apraxia). Methods 77 subjects were included: 10 PSP, 15 frontotemporal dementia (FTD), 29 Alzheimers disease (AD) and 23 normal controls. The presence of apraxia was an exclusion criterion. All patients underwent a detailed neuropsychological examination, and cognitive performance was correlated to the applause sign. Results All patient groups showed the applause sign and differed significantly from normal subjects who were error free. No difference was found when comparing PSP with FTD and FTD with AD. AD differed significantly from PSP but they were not error free (31% of patients with AD showed the applause sign). The only correlation with background neuropsychology was found for measures of executive functions. Conclusions The presence of the applause sign in cortical dementia does not confirm the specificity of the applause sign for parkinsonian disorders. The applause sign should be interpreted as a sign of frontal lobe dysfunction rather than a form of apraxia, and can likely be detected in any kind of disease which involves frontal lobe structures to some extent.

Famous faces and voices: Differential profiles in early right and left semantic dementia and in Alzheimer's disease

Background: Famous face and voice recognition is reported to be impaired both in semantic dementia (SD) and in Alzheimers Disease (AD), although more severely in the former. In AD a coexistence of perceptual impairment in face and voice processing has also been reported and this could contribute to the altered performance in complex semantic tasks. On the other hand, in SD both face and voice recognition disorders could be related to the prevalence of atrophy in the right temporal lobe (RTL). Objective: The aim of the present study was twofold: (1) to investigate famous faces and voices recognition in SD and AD to verify if the two diseases show a differential pattern of impairment, resulting from disruption of different cognitive mechanisms; (2) to check if face and voice recognition disorders prevail in patients with atrophy mainly affecting the RTL. Materials: To avoid the potential influence of primary perceptual problems in face and voice recognition, a pool of patients suffering from early SD and AD were administered a detailed set of tests exploring face and voice perception. Thirteen SD (8 with prevalence of right and 5 with prevalence of left temporal atrophy) and 25 CE patients, who did not show visual and auditory perceptual impairment, were finally selected and were administered an experimental battery exploring famous face and voice recognition and naming. Twelve SD patients underwent cerebral PET imaging and were classified in right and left SD according to the onset modality and to the prevalent decrease in FDG uptake in right or left temporal lobe respectively. Correlation of PET imaging and famous face and voice recognition was performed. Results: Results showed a differential performance profile in the two diseases, because AD patients were significantly impaired in the naming tests, but showed preserved recognition, whereas SD patients were profoundly impaired both in naming and in recognition of famous faces and voices. Furthermore, face and voice recognition disorders prevailed in SD patients with RTL atrophy, who also showed a conceptual impairment on the Pyramids and Palm Trees test more important in the pictorial than in the verbal modality. Finally, in 12SD patients in whom PET was available, a strong correlation between FDG uptake and face‐to‐name and voice‐to‐name matching data was found in the right but not in the left temporal lobe. Discussion: The data support the hypothesis of a different cognitive basis for impairment of face and voice recognition in the two dementias and suggest that the pattern of impairment in SD may be due to a loss of semantic representations, while a defect of semantic control, with impaired naming and preserved recognition might be hypothesized in AD. Furthermore, the correlation between face and voice recognition disorders and RTL damage are consistent with the hypothesis assuming that in the RTL person‐specific knowledge may be mainly based upon non‐verbal representations. HighlightsWe investigated naming and recognition of famous faces and voices in SD and AD.SD patients were impaired both in naming and recognition of famous faces and voices.In SD people recognition disorders were associated to a right temporal lobe atrophy.AD patients were significantly impaired in naming, but not in recognition tests.

Applause sign in Alzheimer's disease: relationships to cognitive profile and severity of illness.

The present study aims to investigate the potential clinical utility of applause sign in Alzheimer’s disease (AD), exploring whether it is consequent to the severity of cognitive impairment or to specific neuropsychological profiles. According to the current debate, the role of apraxia is also investigated. A total of 105 patients with AD were enrolled and classified on the basis of the severity of the disease: 37 had mild AD, 38 moderate AD, and 30 severe AD. They were compared to 42 normal subjects. The applause sign was detected using the three clap test. All patients underwent a broad neuropsychological examination and 95 AD patients were tested for the presence of apraxia with a detailed praxis battery. Applause sign was present in all AD patient groups, which showed a significant difference with respect to normal controls, but not between each other. No significant difference was reported between apraxic and non-apraxic patients. Applause sign correlated with measures of frontal lobe dysfunction. No correlations were found between the applause sign and other cognitive functions examined.

The neural correlates of road sign knowledge and route learning in semantic dementia and Alzheimer's disease

Background Although there is a growing body of research on driving and Alzheimers disease (AD), focal dementias have been understudied. Moreover, driving has never been explored in semantic dementia (SD). Methods An experimental battery exploring road sign knowledge and route learning was applied to patients with SD and AD selected in the early-moderate stage of disease and to a group of healthy participants. Neuropsychological data were correlated to cerebral hypometabolism distribution, investigated by means of positron emission tomography. Results The two dementias showed opposite profiles. Patients with SD showed poor road sign knowledge and normal performance in route learning. By contrast, patients with AD showed low performance in route learning test with preservation of semantic knowledge of road signs. In SD, there was a correlation of semantic knowledge impairment with hypometabolism in the left temporolateral cortex. No correlation between the AD region of interests (ROIs) and the relevant behavioural indices was found, while in the whole-brain analysis there was a significant correlation between route learning and the superior frontal gyrus. Discussion and conclusions For the first time, driving skills were explored in SD, and it is showed a differential profile from the one detected in AD. We demonstrate that the left anterior temporal cortex is implicated in road sign knowledge, while a distributed cortical network, including the frontal cortex, is likely to process route learning.

To clap or not to clap? Applause sign in apathetic and disinhibited/stereotypical behavioural variants of FTD

The nature of the applause sign, that is, the tendency to perform an automatic series of claps in response to the instructions to clap three times, has not been fully understood.1 The behavioural variant of frontotemporal dementia (bvFTD) is a good model to assess the influence of the frontal lobe dysfunction in generating the applause sign. Applause sign in FTD is a debated issue: its frequency ranges from 0% to 60% in different case series.1 ,2 BvFTD entails two distinct phenotypical patterns depending on the behavioural changes the patients show and on the distribution of atrophy3: the apathetic bvFTD, characterised by loss of initiative and volition, inertia and apathy, and the disinhibited bvFTD characterised by hyperactivity, verbal and motor disinhibition. A third rare variant has been reported as the ‘stereotypical variant’ which is mainly characterised by aberrant motor behaviour with perseverations, mannerisms and rituals.3 Rarely repetitive behaviour can be found in the apathetic variant. By contrast, complex repetitive behavioural routines are often present in the disinhibited variant suggesting that the disinhibited and stereotypical variants tend to overlap.3 Although the atrophy spreads across the frontotemporal lobes, the distribution of atrophy tends to be more pronounced in the dorsolateral prefrontal cortex in apathetic bvFTD, in the orbitofrontal frontal cortex in the disinhibited bvFTD,4 and in the frontostriatal cortex in the stereotypical bvFTD, respectively.3 The present study aimed to verify the hypothesis that the applause sign arises from an aberrant motor behaviour. Accordingly, it is expected to be a frequent sign of the disinhibited and stereotypical variants. The apathetic variant, characterised …

Semantic Corticobasal Dementia: Challenging Nosology in Frontotemporal Lobe Degeneration.

Luzzi, Simona Fabi, Katia Cafazzo, Viviana Fringuelli, Fabio M Reverberi, Carlo Baldinelli, Sara Silvestrini, Mauro Provinciali, Leandro Ascoli, Giorgio Pickering-Brown, Stuart Mann, David Neary, David Snowden, Julie S 089701/Wellcome Trust/United Kingdom G0701441/Medical Research Council/United Kingdom Alzheimer Dis Assoc Disord. 2015 Oct-Dec;29(4):360-3. doi: 10.1097/WAD.0000000000000064.