What bilateral damage of the superior parietal lobes tells us about visual attention disorders in developmental dyslexia.

Neuroimaging studies have identified the superior parietal lobules bilaterally as the neural substrates of reduced visual attention (VA) span in developmental dyslexia. It remains however unclear whether the VA span deficit and the deficits in temporal and spatial attention shifting also reported in dyslexic children reflect a unitary spatio-temporal deficit of attention - probably linked to general posterior parietal dysfunction- or the dysfunction of distinct attentional systems that relate to different neural substrates. We explored this issue by testing an adult patient, IG, with a specific damage of the bilateral superior parietal lobules after stroke, on tasks assessing the VA span as well as temporal and spatial attention shifting. IG demonstrated a very severe VA span deficit, but preserved temporal attention shifting. Exogenous spatial orientation shifting was spared but her performance was impaired in endogenous attention. The overall findings show that distinct sub-systems of visual attention can be dissociated within the parietal lobe, suggesting that different attentional systems associated with specific neural networks can be selectively impaired in developmental dyslexia.

[Specificities of the logopenic variant of primary progressive aphasia]. / Particularités du variant logopénique au sein des aphasies progressives primaires.

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved.

Deficits in egocentric-updating and spatial context memory in a case of developmental amnesia.

Patients with developmental amnesia usually suffer from both episodic and spatial memory deficits. DM, a developmental amnesic, was impaired in her ability to process self-motion (i.e., idiothetic) information while her ability to process external stable landmarks (i.e., allothetic) was preserved when no self-motion processing was required. On a naturalistic and incidental episodic task, DM was severely and predictably impaired on both free and cued recall tasks. Interestingly, when cued, she was more impaired at recalling spatial context than factual or temporal information. Theoretical implications of that co-occurrence of deficits and those dissociations are discussed and testable cerebral hypothesis are proposed.

Impaired cerebral vasoreactivity to CO2 in Alzheimer's disease using BOLD fMRI.

OBJECTIVE: To evaluate the cerebral vasoreactivity using blood oxygenation level dependent functional MRI during carbogen inhalation with 7% CO(2) in Alzheimer's disease and amnestic mild cognitive impairment. PARTICIPANTS AND METHODS: Thirty nine subjects were included to be investigated using blood oxygenation level dependent (BOLD) functional MRI at 1.5T during a block-design carbogen inhalation paradigm, with a high concentration face-mask under physiological monitoring. Basal cerebral perfusion was measured using pulsed arterial spin labeling. Image analyses were conducted using Matlab® and SPM5 with physiological regressors and corrected for partial volume effect. RESULTS: Among selected participants, 12 subjects were excluded because of incomplete protocol, leaving for analysis 27 subjects without significant microangiopathy diagnosed for Alzheimer's disease (n=9), amnestic mild cognitive impairment (n=7), and matched controls (n=11). No adverse reaction related to the CO(2) challenge was reported. Carbogen inhalation induced a whole-brain signal increase, predominant in the gray matter. In patients, signal changes corrected for gray matter partial volume were decreased (0.36±0.13% BOLD/mmHg in Alzheimer's disease, 0.36±0.12 in patients with mild cognitive impairment, 0.62±0.20 in controls). Cerebral vasoreactivity impairments were diffuse but seemed predominant in posterior areas. The basal hypoperfusion in Alzheimer's disease was not significantly different from patients with mild cognitive impairment and controls. Among clinical and biological parameters, no effect of apoE4 genotype was detected. Cerebral vasoreactivity values were correlated with cognitive performances and hippocampal volumes. Among age and hippocampal atrophy, mean CVR was the best predictor of the mini-mental status examination. CONCLUSION: This BOLD functional MRI study on CO(2) challenge shows impaired cerebral vasoreactivity in patients with Alzheimer's disease and amnestic mild cognitive impairment at the individual level. These preliminary findings using a new MRI approach may help to better characterize patients with cognitive disorders in clinical practice and further investigate vaso-protective therapeutics.

CSF biomarkers in posterior cortical atrophy.

OBJECTIVE: To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to clinical and neuropsychological assessment. METHODS: This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid ß (Aß(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology. RESULTS: At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD. CONCLUSIONS: PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.

Verb production during action naming in semantic dementia.

UNLABELLED: In contrast with widely documented deficits of semantic knowledge relating to object concepts and the corresponding nouns in semantic dementia (SD), little is known about action semantics and verb production in SD. The degradation of action semantic knowledge was studied in 5 patients with SD compared with 17 matched control participants in an action naming task based on video clips. The pattern of errors, involving a huge proportion of generic verbs (e.g. "to remove" versus "to peel") relative to responses in control subjects, suggested a hierarchical, bottom-up deficit of action knowledge in SD patients. In addition, abnormal responses in patients consisted of verbs that were semantically related to the expected verbs produced by control subjects (e.g. "to undress" versus "to peel" for the action [To peel_orange]). This study suggests that, in SD, non-canonical responses to action naming reflect lack of both specificity and semantic relatedness relative to the expected responses. LEARNING OUTCOMES: As a result of this activity, readers will recognize that semantic word knowledge disappears in semantic dementia using video clips of object-related actions. As a result of this activity, readers will discover that this semantic impairment followed a hierarchical pattern with the more specific verbs vanishing first.

Mild Alzheimer's disease: a "position paper".

Under the auspices of the Societe Francaise de Geriatrie et Gerontologie, a multi-disciplinary group of specialists in geriatrics, neurology, epidemiology, psychiatry, neuroradiology and nuclear medicine met with the aim of drawing up references on the methods for diagnosing and treating mild Alzheimer's disease. The critical analysis of international literature, conducted by Professor Bruno Vellas for the scientific committee, has served to support study of the latest knowledge in 2008. The multi-disciplinary group met on 14 and 15 May 2008 in order to set out the questions that this study must answer and to allocate draft studies. Thus, it has been possible to conduct a study focused on mild Alzheimer's disease, giving particular attention to diagnostic procedure, specific methods of treatment and the benefits of making a diagnosis.

[Ethics and dementia: a three years' experience of a French "Alzheimer's ethico-clinic workshop"]. / Ethique et démence: une expérience de trois ans de l'Espace éthique Alzheimer grenoblois.

There is a growing interest concerning ethical questions. This ethical need is the more important in the field of dementia. Indeed, the ethical concerns related to this field are highly specific, which leaves some of our questions without pertinent answers. METHODS: After three years of experience, it is a good time to assess the Alzheimer ethico-clinic workshop created by a French memory centre (in Grenoble) and encouraged by the French national Alzheimer disease plan. RESULTS: Since their implementation, we have recorded 24 monthly coordination meetings, 10 of which have been held through videoconferences with various participants. Most of the time during the workshops, clinical situations that are experienced in our daily activities are brought up by one of us and then exposed for collective discussion. If no practical situation is available, we organize the meetings through critical readings of texts of law or through comments on articles dealing with Ethics. We retain four main ethical topics: the information given to the patient and his family, the acceptance of the person, the balance of benefits/risks and one's individual ethics as opposed to the ethics of a group. At this point in time, we are pleased with the organization of these workshops and feel that they meet our expectations. Thanks to the diverse experiences and activities of each participant, the discussions on Ethics are of high quality. PROSPECTIVES: As a place of shared discussions/thoughts, these ethical workshops could constitute a reference to be used when making decisions in complex situations. Other than the importance of the ethical questions that are raised, it should encourage open-minded attitudes and enrich the actions of each of us by making us more aware of the ethical concerns in daily situations. Finally, these workshops could be a field of research for theses, dissertations and answer the training and research needs of a memory centre.

Associative visual agnosia: a case study.

We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

[Semantic dementia: reflexions of a French working group for diagnostic criteria and constitution of a patient cohort]. / Démence sémantique: réflexions d'un groupe de travail pour des critères de diagnostic en français et la constitution d'une cohorte de patients.

Semantic dementia (SD) is a syndrome of progressive loss of semantic knowledge for objects and people. International criteria propose that SD be included in the frontotemporal lobar degeneration syndromes, with progressive non-fluent aphasia and frontotemporal dementia (FTD). However, several related syndromes have been defined that clinically and conceptually share both similarities and differences with SD: fluent progressive aphasia, progressive prosopagnosia, temporal variant of FTD. In order to establish a French consensus for the diagnosis and modalities of evaluation and follow-up of SD, a working group, composed of neurologists, neuropsychologists and speech-therapists, was established by the Groupe de réflexion sur les évaluations cognitives (GRECO). New criteria were elaborated, based on clinical, neuropsychological, and imaging data. They define typical and atypical forms of SD. A diagnosis of typical SD relies on an isolated and progressive loss of semantic knowledge, attested by a deficit of word comprehension and a deficit of objects and/or people identification, with imaging showing temporal atrophy and/or hypometabolism. SD is atypical if the deficit of semantic knowledge is present only within a single modality (verbal versus visual), or if non-semantic deficits (mild and not present at onset) and/or neurological signs, are associated with the semantic loss.

Cortico-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): about two case reports characterized by a gap between the diagnosis of autoimmune thyroiditis and neurological disorders.

We report two cases of steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) often called "Hashimoto's encephalopathy" in which the neurological manifestations develop years before or after the Hashimoto's diagnosis. Because of this specific presentation, the etiological diagnosis of this type of encephalopathy can be a difficult task. In our patients there was a gap of 10 to 20 years between the proof of autoimmune thyroiditis and the neurological symptoms. Case reports of this type of presentation are rare in the literature. A dramatic responsiveness to steroids with total recovery, after several relapses, was confirmed 3 years after the end of treatment. We suggest that antithyroid antibodies should be checked in all patients with unexplained acute or subacute encephalopathy even in elderly subjects in whom the most important differential diagnosis with Creutzfeldt-Jacob disease remains rapidly progressive Alzheimer's disease. A brief review of the literature is proposed.

Influence of motor disorders on the visual perception of human movements in a case of peripheral dysgraphia.

We report the case of a 71 year-old female patient (DC) with a left parietal lesion resulting in a peripheral dysgraphia essentially characterized by difficulties in letter sequences writing. The aim of our experiments was to analyze the influence of motor difficulties on the visual perception of both writing and reaching movements. Results showed a strong link between motor and perceptual performance. For reaching movements, performances in both production and perception tasks conform to the motor principles identified in healthy subjects (Fitts' law and motor anticipation). By contrast, for handwriting movements, DC's productions do not follow the motor principles usually observed in normal subjects (isochrony principle, motor anticipation) and in perception the same results were observed. The motor references used by DC in the visual perception of writing movement were not the laws of movement but rather her own way of writing. Taken together these data strongly suggest that motor competences is involved in the visual perception of human movements. They are discussed in the general framework of the simulation theory.

Are semantic errors actually semantic?: Evidence from alzheimer's disease.

Patients with Alzheimer's disease (AD) produce a high rate of semantic errors when naming to confrontation. This is considered to be one of the many consequences of their semantic memory deficit. However, it has been shown, in aphasic patients with focal lesions, that semantic errors could arise from impairment to any one of the levels in the naming process. To check this hypothesis in AD, we assessed in 15 patients the capacity to name and access semantic knowledge (by multiple-choice probe questions) about 14 objects presented successively in the visual, tactile, auditory, and verbal modalities. In the visual naming task, 33 errors were recorded: 26 (78.8%) were semantic and 7 (21.2%) were unrelated errors. Of the 26 semantic errors, 8 were related to a deficit of the semantic knowledge related to the item and 17 to a deficit in the retrieval of the phonological form of the word. One was associated with a deficit of access to semantic knowledge in the visual modality. The 7 unrelated errors were associated with a loss of semantic knowledge for 4 and deficit of access to the phonological form for 3. In conclusion, this study shows that semantic errors do not systematically reflect a deficit of semantic knowledge in Alzheimer's disease. It also seems that unrelated errors are more frequently related to semantic deficits than semantic errors in this population.

Superior written over spoken picture naming in a case of frontotemporal dementia.

Two main hypotheses have been proposed regarding the role of phonology in written word production. According to the phonological mediation hypothesis, the retrieval of the lexical phonological representation of a word is an obligatory prerequisite to the retrieval of its spelling. Therefore, deficits to the phonological lexicon should affect both spoken and written picture naming. In contrast, the orthographic autonomy hypothesis posits that the lexical orthographic representations of words can be accessed without any necessary phonological mediation. In support of this view, cases of preserved written naming despite impaired lexical phonology have been reported following brain damage. In this report, we replicate this basic pattern of performance in case YP, a 60-year-old woman with a pattern of frontotemporal dementia. As her disease progressed, YP's ability to write down the names of pictures remained very good despite a severe decline in oral naming. Further testing indicated that this deficit was not primarily due to an articulatory or post-lexical phonological deficit. YP's case provides strong additional support for the orthographic autonomy hypothesis. The significance of this case with respect to the characterization of dementia syndromes is discussed.

Working memory functioning in medicated Parkinson's disease patients and the effect of withdrawal of dopaminergic medication.

Cognitive impairments in Parkinson's disease (PD) could be explained by a central executive (CE) deficit in A. D. Baddeley's (1986) working memory model. To test this hypothesis, verbal, spatial, and double span tasks were given to 12 medicated PD patients and control participants, with varying recall delays. The double span task was assigned to explore the coordinating and integrating function of the CE, and lengthening the recall delay was expected to implicate more attentional resources. PD patients had lower spans relative to controls in all tasks. However, the more specific implication of the CE was difficult to prove. One reason could be that PD patients were on dopaminergic treatment when tested. To control this effect, 12 PD patients on and off medication were studied in a second experiment using the same tasks. PD patients off medication had lower spans only in the double task; this result underlines the role of dopamine on working memory processes.

Neuropsychological functioning among non-psychotic siblings and parents of schizophrenic patients

Several studies have shown subtle neuropsychological deficits in healthy relatives of schizophrenic patients. However, older relatives and parents have been less frequently assessed than younger adult relatives and siblings. Furthermore, some areas of neuropsychological functioning such as memory and learning have been little studied. Thirty-seven 22-70-year-old non-psychotic parents and siblings of schizophrenic patients were compared to 37 healthy control subjects on a battery of neuropsychological tests (Trail Making, parts A and B, verbal fluency, Wisconsin Card Sorting Test, and four subtests of the Wechsler Memory Scale-Revised: logical memory, design reproduction, verbal paired associates and digit span). Relatives did not differ from control subjects on Wisconsin Card Sorting Test performance and on visual memory, but were significantly impaired on verbal fluency; more subtle deficits were found on Trail Making, part B, digit span and paired associates. A higher proportion of relatives than control subjects showed impairment on verbal fluency and verbal memory. These neuropsychological weaknesseswere present as much in siblings as in parents of schizophrenic patients, and age did not cancel differences between relatives and control subjects. Thus, these subtle deficits seem to be potential phenotypic markers of schizophrenia.

Identification without manipulation: a study of the relations between object use and semantic memory.

The role of semantic knowledge in object utilisation is a matter of debate. It is usually presumed that access to semantic knowledge is a necessary condition for manipulation, but a few reports challenged this view. The existence of a direct, pre-semantic route from vision to action has been proposed. We report the case of a patient with a disorder of object use in everyday life, in the context of probable Alzheimer's disease. This patient was also impaired when manipulating single objects. He showed a striking dissociation between impairment in object use and preserved capacity to perform symbolic and meaningless gestures. To elucidate the nature of the disorder, and to clarify the relations between semantic knowledge and object use, we systematically assessed his capacity to recognise, name, access semantic knowledge, and use 15 common objects. We found no general semantic impairment for the objects that were not correctly manipulated, and, more importantly, no difference between the semantic knowledge of objects correctly manipulated and objects incorrectly manipulated. These data, although not incompatible with the hypothesis of a direct route for action, are better accommodated by the idea of a distributed semantic memory, where different types of knowledge are represented, as proposed by Allport (Allport, D. A. Current perspectives in dysphasia, pp. 32-60. Churchill Livingstone, Edinburgh, 1985).

[Absence of frontal lobe dysfunction and working memory deficits in young schizophrenic patients]. / Absence de dysfonctionnement frontal et de trouble de la mémoire de travail chez de jeunes schizophrènes.

The impairment in tasks requiring intact frontal lobe functions has been repeatedly shown in schizophrenics. However, the relative roles of confounding factors, like duration of the disease, social withdrawal, or antidopaminergic medication, are not clearly demonstrated. We studied the performance of 12 young active patients, with chronic residual schizophrenia that had recent onset, and 12 control subjects, with frontal lobe tests and with a battery designed to explore working memory. The results show normal performance in schizophrenia. The small number of patients does not allow definitive conclusions, but this study suggests that a frontal dysfunction may not be present early in the evolution of schizophrenia in active patients.