Serge Belliard

Impaired memory is a hallmark of prodromal Alzheimer’s Disease (AD). Prior knowledge associated with the memoranda has proved to have a powerful effect on memory in healthy subjects. Yet, barely nothing is known about its effect in early AD. We used functional MRI to ask whether prior knowledge enhanced memory encoding in early AD and whether the nature of prior knowledge mattered. Early AD patients and healthy controls underwent a task-based fMRI experiment, being scanned while learning face-scene associations. Famous faces carried Pre-Experimental Knowledge (PEK) while unknown faces repeatedly familiarized prior to learning carried Experimental Knowledge (EK). As expected, PEK increased subsequent memory in healthy elderly. However, patients did not benefit from PEK. Partly non-overlapping brain networks supported PEK vs. EK encoding in healthy controls. Patients displayed impaired activation in a right subhippocampal region where activity predicted successful associative memory formation of PEK stimuli. These findings call for a thorough consideration of how prior knowledge impacts learning and suggest a possible underestimation of the extent of associative memory impairment in early AD. Highlights: Learning is impaired in prodromal AD, but we currently ignore whether prior knowledge available at encoding promotes learning in AD as it does in healthy controls. Patients with AD failed to benefit from pre-experimental prior knowledge (famous faces) by comparison with experimental knowledge (unknown but familiarized faces). fMRI responses at study revealed distinct networks underlying associative encoding for both pre-experimental and experimental knowledge. A subsequent memory effect found in control subjects for associations carrying pre-experimental knowledge in the right subhippocampal structures, including the perirhinal cortex, was absent in patients. Pre-experimental knowledge-based associative encoding relies on brain regions specifically targeted by early tau pathology. Using unfamiliar materials to probe memory in early AD might underestimate learning impairment.

SUMMARY: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is an autosomal dominant leukoencephalopathy related to CSF1R gene mutations. A growing number of clinicoradiologic phenotypes have been described. In this study, we analyzed brain imaging findings in 16 patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia to refine radiologic diagnostic clues. T2/FLAIR white matter hyperintensities were present in all patients with frontal or frontoparietal predilection, with asymmetric distribution in more than one-third. Brain atrophy and callosal involvement were almost constant, and corticospinal tract involvement was frequent. Moreover, deep white matter hyperintense dots on DWI and deep punctate calcifications on CT were often found. Conversely, deep gray matter nuclei, external capsules, and brain stem were rarely involved. Our series emphasized the great variability of MR imaging findings seen in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. A complete imaging screening including DWI, T2*, and CT is mandatory to accurately assess patients with suspected inherited adult-onset leukoencephalopathy.

Semantic dementia patients seem to have better knowledge of information linked to the self. More specifically, despite having severe semantic impairment, these patients show that they have more general information about the people they know personally by direct experience than they do about other individuals they know indirectly. However, the role of direct personal experience remains debated because of confounding factors such as frequency, recency of exposure, and affective relevance. We performed an exploratory study comparing the performance of 5 semantic dementia patients with that of 10 matched healthy controls on the recognition (familiarity judgment) and identification (biographic information recall) of personally familiar names versus famous names. As expected, intergroup comparisons indicated a semantic breakdown in semantic dementia patients as compared with healthy controls. Moreover, unlike healthy controls, the semantic dementia patients recognized and identified personally familiar names better than they did famous names. This pattern of results suggests that direct personal experience indeed plays a specific role in the relative preservation of person-specific semantic meaning in semantic dementia. We discuss the role of direct personal experience on the preservation of semantic knowledge and the potential neurophysiological mechanisms underlying these processes.

Semantic Dementia (SD) is a subject of a rich literature, but few large series are available. We report the demographics and neuropsychological data of a cohort of 82 patients followed prospectively for 20 years. Semantic Dementia begins before age 65 in 75 % of cases, but we have hold this diagnosis in two subjects over 80 years. In accordance with the classification of the French consensus of 2008, initially 71 % of patients could be classified as typical SD with an isolated, multimodal semantic memory impairment. 11 % could be classified as atypical SD due to pure verbal semantic impairment and 18 % as atypical SD because of the existence of discrete extralinguistic disorders (type 2). Two years later, 28.5 % of typical SD exhibited extralinguistic disturbances and all initial pure verbal SD exhibited multimodal semantic memory impairment. Although classified as a subtype of progressive aphasia, SD is more than a semantic verbal deficit in the vast majority of cases.

La démence sémantique (DS) est caractérisée par des troubles majeurs de la mémoire sémantique et par des modifications du comportement, notamment l’émergence d’un égocentrisme comportemental qui désigne la propension de ces patients à se référer à leur propre personne. Ce travail se donnait pour objectif de mieux comprendre les processus qui sous-tendent ce phénomène chez un patient, L.G., en procédant à une évaluation conjointe des comportements égocentriques, de l’égocentrisme cognitif, désignant le meilleur maintien des représentations sémantiques colorées par l’expérience personnelle (EP) par rapport aux autres connaissances et de la théorie de l’esprit (ToM, pour theory of mind) dont l’altération pourrait engendrer la perte des conventions sociales observée dans cette affection. L’égocentrisme comportemental était évalué grâce à un questionnaire spécialement conçu pour cette étude. L’égocentrisme cognitif était mesuré en comparant les connaissances disponibles sur les personnes familières à celles se rapportant à des personnes célèbres dans des tâches de décision de familiarité et d’identification. La ToM était évaluée à l’aide d’épreuves d’attribution d’intentions et d’états mentaux affectifs, de fausses croyances et de jugement de préférence. Cet examen montre une augmentation significative des comportements égocentriques, un bénéfice de l’EP sur les performances de mémoire sémantique et une altération de l’attribution de fausses croyances et du jugement de préférence. L’égocentrisme comportemental pourrait naître de l’existence conjointe de l’égocentrisme cognitif et de troubles de ToM. De futurs travaux portant sur ces dimensions devraient permettre de mieux comprendre les mécanismes sous-jacents aux modifications comportementales observées dans la DS.