Didier Maillet

Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in patients with primary Sjögren syndrome: a case–control study

Objectives: To assess subclinical central nervous system (CNS) involvement in primary Sjögren syndrome (pSS), by comparing standard brain MRI, in-depth neuropsychological testing and 99mTc-ECD brain single-photon emission computed tomography (SPECT) of patients with pSS with matched controls. Methods: 10 women (<55 years old), with pSS defined using European–American criteria, presence of anti-SSA and/or anti-SSB antibodies and no history of neurological involvement were prospectively investigated, and compared with 10 age- and sex-matched controls. All subjects underwent, within 1 month, brain MRI, neuropsychological testing, including overall evaluation and focal cognitive function assessment, and 99mTc-ECD brain SPECT. Results: 99mTc-ECD brain SPECT abnormalities were significantly more common in patients with pSS (10/10) than controls (2/10; p<0.05). Cognitive dysfunctions, mainly expressed as executive and visuospatial disorders, were also significantly more common in patients with pSS (8/10) than controls (0/10; p<0.01). Notably, between-group comparisons enabled a significant correlation to be established between neuropsychological assessment and 99mTc-ECD brain SPECT abnormalities in patients with pSS (rs = 0.49, p<0.01). MRI abnormalities in patients and controls did not differ significantly. Conclusions: Neuropsychological testing and 99mTc-ECD brain SPECT seem to be the most sensitive tools to detect subclinical CNS dysfunction in pSS. The strong correlation between cortical hypoperfusion in 99mTc-ECD brain SPECT and cognitive dysfunction suggests an organic aetiology of CNS dysfunction in pSS. These data should be confirmed in a larger study.

Music enhances verbal episodic memory in Alzheimer’s disease

Introduction: Although previous studies suggest that music may facilitate verbal learning in a healthy population, such a mnemonic effect has seldom been investigated in Alzheimer’s disease (AD). Moreover, memorization of texts was generally compared when either sung or spoken. In the present study, it was examined whether the benefit observed on verbal learning was specific to music or whether an associative context binding items together led to similar benefits, regardless of the nature of the association. Method: Twelve patients with mild AD and 15 healthy controls learned texts presented with either a musical (sung) or a nonmusical association (spoken associated to a silent movie sequence) or without association (spoken alone). Immediate and delayed (after a 5-min delay) recall was measured. Results: Main results showed that (a) sung texts were better remembered than spoken texts, both immediately and after a retention delay, for both groups; (b) the musical benefit was robust, being observed in most AD patients; (c) the nonmusical association may also facilitate verbal learning but to a lesser extent. Conclusions: A musical association during the encoding stage facilitates learning and retention in AD. Furthermore, this advantage seemed quite specific to music. The results are discussed with respect to the clinical applications in AD; theoretical implications are highlighted to explain the power of music as a mnemonic technique.

Evaluation des capacités de mémoire épisodique de sujets âgés illettrés

Assessing cognitive functions in illiterate people is a difficult task because most of the neuropsychological tests exploring episodic memory have been validated in formally educated people, are based on verbal material and, therefore, require a good knowledge of language. Two episodic memory tests (TNI93 and TMA93) designed to be used for cognitive impairment screening in illiterate people have been designed, then validated in a multicultural low-educated population. Four hundred and thirty seven subjects aged 60 and over, living in the Seine-Saint-Denis district, received a medical check up offered by the National Health Service and their episodic memory performance was examined with these screening tests. The performance obtained on these tests depends both on age and educational level, as expected. Normative data for screening purpose in population with low education and/or not fluent with the language of the examiner are presented.

Posterior Cortical Atrophy as an Extreme Phenotype of GRN Mutations

IMPORTANCE Posterior cortical atrophy (PCA) is characterized by progressive visuoperceptual and visuospatial deficits and commonly considered to be an atypical variant of Alzheimer disease. Mutations of the GRN gene are responsible for a large phenotypic spectrum, but, to our knowledge, the association of PCA with GRN mutations has never been described. OBSERVATIONS We studied a patient presenting with insidious impairment of basic visuoperceptual skills and apperceptive visual agnosia with predominant posterior atrophy corresponding to a visual/ventral variant of PCA. A heterozygous p.Arg110* (c.328C>T) GRN mutation was identified in this patient. CONCLUSIONS AND RELEVANCE This study extends the clinical spectrum of GRN mutations that may be responsible for a PCA phenotype. The GRN phenotypes overlap other degenerative dementias and highlight the limits of actual nosologic boundaries in dementias. The GRN gene should be analyzed in patients with PCA, particularly when the damage progresses to anterior cerebral regions and a family history of dementia is present.

L’atrophie corticale postérieure

Posterior cortical atrophy belongs to the progressive focal atrophy group of neurodegenerative diseases. It is characterized by specific clinical deficits in visual perception, which can affect either visuo-spatial features or identity of objects. The posterior cortical atrophy, initially described by Pick in 1902, is a rare and not well known syndrome. While it is easy to differentiate posterior cortical atrophy from Alzheimers disease, some cognitive deficits are common with those of Lewy body disease and corticobasal degeneration, which results in diagnostic mistakes. This paper proposes a synthetic review of the posterior cortical atrophy illustrated by a clinical case.

Superficial siderosis of the central nervous system: a rare cause of dementia with therapeutic consequences

A 75-year-old patient was evaluated for dementia. His past medical history included an ischaemic cardiomyopathy treated with aspirin daily. His neurological examination showed mild ataxia syndrome and central deafness. The neuropsychological examination did not suggest Alzheimers disease. No specific aetiology was found from biological investigations, but MRI scans revealed a superficial siderosis, which was further confirmed with CSF exams. This case highlights the interest of MRI with echo-gradient-T2 weighted sequences in patients investigated for memory disorders. Once the diagnosis is known, specific preventive measures have to be taken: searching for a treatable source of bleeding and the interruption of antiplatelet aggregation or anticoagulant treatments.

Detection of 1st- and 2nd-order Temporal-envelope Cues in a Patient With Left Superior Cortical Damage

This psychophysical study explores the extent to which the auditory cortex is necessary for various aspects of temporal-envelope perception, that is, perception of the slow temporal modulations in amplitude known to be crucial for sound identification. The ability to detect 1st- and 2nd-order sinusoidal amplitude modulation (AM) is evaluated in a single patient showing left-hemisphere damage encroaching the primary and secondary auditory cortices. Here, 1st- and 2nd-order AM refer to (1) sinusoidal variation in the amplitude of a 2 kHz pure tone, and (2) sinusoidal variation in the depth of a 64 Hz AM applied to the 2 kHz pure tone, respectively. The results replicate previous findings by showing that damage to the left auditory cortex results in a selective deficit in auditory sensitivity to the lowest 1st-order AM (i.e., 1st-order AM frequencies ≤ 16 Hz). Moreover, a dissociation is apparent between the ability to detect 1st- and 2nd-order temporal-envelope cues. The patient shows poorer than normal ability to detect 2nd-order AM at low frequencies ranging from 4–23 Hz, but normal ability to detect the high (64 Hz) 1st-order AM carrying these 2nd-order modulations. This result indicates that damage to the left primary and secondary auditory cortices affects the ability to detect temporal variations in the local properties of sounds (such as AM depth). It is also consistent with the idea that, as in vision, central nonlinear mechanisms are involved in the computation of such local (or 2nd-order) temporal properties.

L’intelligence artificielle à la rencontre de la neuropsychologie : mémoire sémantique, vieillissement normal et pathologique

Artificial intelligence (IA) is the subject of much research, but also many fantasies. It aims to reproduce human intelligence in its learning capacity, knowledge storage and computation. In 2014, the Defense Advanced Research Projects Agency (DARPA) started the restoring active memory (RAM) program that attempt to develop implantable technology to bridge gaps in the injured brain and restore normal memory function to people with memory loss caused by injury or disease. In another IAs field, computational ontologies (a formal and shared conceptualization) try to model knowledge in order to represent a structured and unambiguous meaning of the concepts of a target domain. The aim of these structures is to ensure a consensual understanding of their meaning and a univariant use (the same concept is used by all to categorize the same individuals). The first representations of knowledge in the AIs domain are largely based on model tests of semantic memory. This one, as a component of long-term memory is the memory of words, ideas, concepts. It is the only declarative memory system that resists so remarkably to the effects of age. In contrast, non-specific cognitive changes may decrease the performance of elderly in various events and instead report difficulties of access to semantic representations that affect the semantics stock itself. Some dementias, like semantic dementia and Alzheimers disease, are linked to alteration of semantic memory. We propose in this paper, using the computational ontologies model, a formal and relatively thin modeling, in the service of neuropsychology: 1) for the practitioner with decision support systems, 2) for the patient as cognitive prosthesis outsourced, and 3) for the researcher to study semantic memory.

P4-27 Hemosiderose superficielle du SNC : Un diagnostic de démence à ne pas négliger

L’Hemosiderose Superficielle du SNC est une pathologie rare (environ 90 cas rapportes dans la litterature) mais dont la frequence dans les demences est vraisemblablement sousestimee. L’Hemosiderose Superficielle du SNC est definie par la presence de depots d’hemosiderine a la surface du systeme nerveux central et est la consequence d’hemorragies sous-arachnoidiennes chroniques ou repetees. La triade caracteristique est constituee par l’association d’une surdite, d’une ataxie cerebelleuse et d’un syndrome pyramidal. Les troubles cognitifs existent dans 24% des observations (Fearnly et al., 1995). Van Harsjamp et al. (2005) rapportent 6 cas ayant un profil cognitif similaire : syndrome dysexecutif (fluences verbales, test de Hayling) et de troubles de la memoire visuelle (rappel de la figure de Rey). Nous rapportons ici le cas d’un patient adresse pour bilan de troubles de la memoire. Mr B., 60 ans, a comme antecedents une HTA, un diabete de type II, deux traumatismes crâniens 18 ans auparavant et une surdite progressive depuis 10 ans. Les troubles cognitifs evoluent depuis plusieurs mois avec a l’admission une desorientation temporo-spatiale, des troubles du langage, un syndrome frontal (grasping, perseverations, comportements d’imitation). L’examen neurologique retrouve un syndrome cerebelleux statique et cinetique. Les tests neuropsychologiques montrent une deterioration cognitive globale : MoCa : 14/30, passation du RL-RI 16 impossible, MIS a 5/8. L’etude du langage retrouve de nombreuses paraphasies verbales et semantiques : DO 80 : 57/80, reduction de la fluence verbale phonologique et semantique, troubles de la lecture. La comprehension est relativement preservee. Il existe une apraxie ideo-motrice. L’IRM cerebrale met en evidence un hyposignal T2 mesencephalique, cerebelleux et de la partie interne des lobes temporaux. L’IRM medullaire retrouve un hyposignal T2 peri-medullaire et du cone terminal. La cause du saignement chronique n’a pas ete retrouvee. Discussion L’Hemosiderose Superficielle du SNC est une cause rare de demence mais potentiellement curable lorsque la cause du saignement est mise en evidence (50% ces cas). Le delai diagnostic apres le premier symptome varie de 1 a 37 ans (Le Rhun et al., 2008). Les anomalies IRM (hyposignal T2) sont la base du diagnostic mais peuvent parfois etre difficiles a mettre en evidence et la sequence echo de gradient T2* apparait comme la plus sensible. Des essais de traitement par chelateurs du fer ont montre des resultats varies et un patient s’est ameliore sous corticoides (le Rhun et al., 2008). L’Hemosiderose Superficielle du SNC contre-indique bien evidemment les antiaggregeants et les anticoagulants.

Episodic memory tests for screening Alzheimer's disease in illiterate and low-educated individuals: Comparison of rural and urban populations

P4-211 EPISODIC MEMORY TESTS FOR SCREENING ALZHEIMER’S DISEASE IN ILLITERATE AND LOW-EDUCATED INDIVIDUALS: COMPARISON OF RURAL AND URBAN POPULATIONS Didier Maillet, Hind Mokhri, H el ene Amieva, Herve Le Clesiau, Catherine Belin, UF Memoire et Maladies Neurodegeneratives, Bobigny, France; ISPED, Bordeaux, France; Centre d’Examens de la Sante, Bobigny, France; CHU Avicenne APHP France, Bobigny, France. Contact e-mail: didier.maillet@avc.aphp.fr