The pattern of cortical thickness associated with executive dysfunction in MCI and SCC: The MEMENTO cohort.

BACKGROUND: The association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC. METHODS: All participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n=1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer. RESULTS: The global executive function score was related to the BPF (sß: 0.091, P<0.001) and CT in the right supramarginal (sß: 0.060, P=0.041) and right isthmus cingulate (sß: 0.062, P=0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P<0.001) and CT in the left parsorbitalis region (sß: 0.045, P=0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P<0.001) and CT in the right supramarginal region (sß: 0.061, P=0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P=0.045) and CT in the right precuneus (sß: 0.073, P=0.019) and right isthmus cingulate region (sß: 0.054, P=0.032). CONCLUSIONS: In a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD.

Brain FDG-PET correlates of saccadic disorders in early PSP.

BACKGROUND: New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. OBJECTIVES: To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. METHODS: Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. RESULTS: Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. CONCLUSIONS: These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.

18F-FDG brain PET hypometabolism in patients with long COVID.

PURPOSE: In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of 18F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection. METHODS: PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints. RESULTS: In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001). CONCLUSION: This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.

From face processing to face recognition: Comparing three different processing levels.

Verifying that a face is from a target person (e.g. finding someone in the crowd) is a critical ability of the human face processing system. Yet how fast this can be performed is unknown. The 'entry-level shift due to expertise' hypothesis suggests that - since humans are face experts - processing faces should be as fast - or even faster - at the individual than at superordinate levels. In contrast, the 'superordinate advantage' hypothesis suggests that faces are processed from coarse to fine, so that the opposite pattern should be observed. To clarify this debate, three different face processing levels were compared: (1) a superordinate face categorization level (i.e. detecting human faces among animal faces), (2) a face familiarity level (i.e. recognizing famous faces among unfamiliar ones) and (3) verifying that a face is from a target person, our condition of interest. The minimal speed at which faces can be categorized (∼260ms) or recognized as familiar (∼360ms) has largely been documented in previous studies, and thus provides boundaries to compare our condition of interest to. Twenty-seven participants were included. The recent Speed and Accuracy Boosting procedure paradigm (SAB) was used since it constrains participants to use their fastest strategy. Stimuli were presented either upright or inverted. Results revealed that verifying that a face is from a target person (minimal RT at ∼260ms) was remarkably fast but longer than the face categorization level (∼240ms) and was more sensitive to face inversion. In contrast, it was much faster than recognizing a face as familiar (∼380ms), a level severely affected by face inversion. Face recognition corresponding to finding a specific person in a crowd thus appears achievable in only a quarter of a second. In favor of the 'superordinate advantage' hypothesis or coarse-to-fine account of the face visual hierarchy, these results suggest a graded engagement of the face processing system across processing levels as reflected by the face inversion effects. Furthermore, they underline how verifying that a face is from a target person and detecting a face as familiar - both often referred to as "Face Recognition" - in fact differs.

Progressive supranuclear palsy and corticobasal degeneration: Diagnostic challenges and clinicopathological considerations.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future.

[Weight loss, dementia and ataxia susceptible to doxycycline: a likely new case report caused by T. whipplei]. / Prise de poids, démence et syndrome cérébelleux sensible à la doxycycline : un probable nouveau cas lié à T. whipplei.

INTRODUCTION: Whipple's disease is a rare infectious disease due to Tropheryma whipplei, a bacterium rarely causing severe localized neurological infection (only 25 cases reported in the literature), which are more often diagnosed by a positive T. whipplei PCR performed on cerebrospinal fluid. CASE REPORT: We report the third case of progressive dementia associated with obesity and ataxia in a 52-year-old man. Classic laboratory results performed to identify the etiology of the clinical features were non-contributive: only a saliva T. whipplei PCR was strongly positive and the Western blot serology has detected an asymptomatic carriage profile. The (18)FDG-PET highlighted a frontal area hypometabolism. An antibiotic treatment by doxycycline allowed a partial regression of the neurological manifestations, a weight loss and a significant improvement of the (18)FDG frontal hypometabolism. CONCLUSION: Progressive dementia associated with ataxia and obesity is a new clinical syndrome caused by T. whipplei. Antibiotic test by doxycycline can help to the diagnosis and (18)-FDG could facilitate the follow-up.

[Use of CSF biomarkers in the diagnosis of Alzheimer's disease in clinical practice]. / Utilisation des biomarqueurs du LCR dans le diagnostic de la maladie d'Alzheimer en pratique clinique.

INTRODUCTION: The diagnosis of Alzheimer's disease (AD) currently relies on clinical criteria that are primarily based on the presence of an amnestic syndrome of the mesial temporal lobe type. In recent years, new diagnostic tools have been developed, such as the possibility of measuring a set of proteins directly involved in the pathophysiological process of AD. A profile suggestive of AD has been defined, characterized by decreased beta-amyloid peptide, combined with increased Tau protein and phopho-Tau. STATE OF KNOWLEDGE: According to current data available in the medical literature, the potential usefulness of CSF biomarkers in the common forms of AD fulfilling usual clinical criteria remains modest. In contrast however, they could be of significant help in the diagnosis of early-onset AD, in particular in atypical forms with prominent non-memory impairment (involving vision, language or behavior). In addition, due to their close relationship with the pathological process, they bring useful prognosis information upon the aggressiveness of the disease. CONCLUSION AND PERSPECTIVE: Taken together, in the current state of knowledge, use of CSF biomarkers in clinical practice should first be recommended for the assessment of early-onset cognitive disturbances, in particular when initial symptoms are of a non-memory type. Their development, however, offers new avenues in the fields of clinical and pharmacological research.

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.

[Isolated autobiographical amnesia: a neurological basis?]. / Amnésie autobiographique isolée : une origine neurologique ?

INTRODUCTION: The term "autobiographical memory" (AuM) refers to contextually bound experiences that occurred in a specific time, place, and affective setting. AuM is a component of memory commonly impaired in amnestic disorders. Alteration occurs rarely in isolation but rather in the setting of a larger memory impairment. Isolated AuM deficit is a controversial clinical entity, however, recently reported in the context of temporal lobe epilepsy. This study aims at characterizing this poorly documented clinical syndrome and at discussing its potential pathophysiological basis. PATIENTS AND METHODS: We studied a group of three subjects with a history of pharmacosensitive epilepsy and severe AuM complaints. They all were submitted to a neuropsychological evaluation that included an extensive episodic memory assessment, along with wake/sleep electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). RESULTS: We observed the following findings: preserved autonomy and intact global cognitive functioning; normal performance to standardized episodic memory assessment, contrasting with decreased performance to specific AuM evaluation; frontal and/or temporal epileptic activity on EEG; and normal structural brain MRI. CONCLUSION: We reported on a group of patients exhibiting selective impairment of some components of personal memory, associated with interictal frontal and/or temporal abnormalities on EEG. To account for these findings, we hypothesise that interictal epileptic-related activity is impeding long-term consolidation or storage of autobiographical material.

[Pure progressive amnesia: an amnestic syndrome with preserved independence in daily life]. / L'amnésie pure progressive : un syndrome amnésique avec préservation de l'autonomie.

INTRODUCTION: Pure progressive amnesia, a form of progressive focal cortical atrophy is thought to represent the early stages of a rare form of Alzheimer's disease (AD). This syndrome is characterized by the insidious and slowly progressive breakdown of memory, in the absence of a significant impairment in other cognitive domains or in the realm of behavior. The aims of the present study were to contribute to the characterization of this poorly documented type of amnesia, to compare it with other forms of amnestic syndromes resulting from lesions to the medial temporal lobes and to discuss its potential pathophysiological basis. PATIENTS AND METHOD: We carried out three single case studies in patients presenting with pure progressive amnesia. They all underwent a neuropsychological evaluation that included an extensive assessment of spatial and recognition memory, along with brain magnetic resonance imaging and a cerebral blood flow study. RESULTS: All three patients had a severe deficit in the storage of context-free information, along with a severe visual recognition memory impairment, as previously reported in a case study on a patient with pure progressive amnesia (Cognitive Neuropsychology 23 (2006) 1230-1247). Yet, spatial memory remained well preserved, and patients maintained totally independent in everyday life. In addition, a significant atrophy of the medial temporal structures was found. DISCUSSION: This specific pattern of impairment differs from other types of amnestic syndromes after medial temporal damage and raises the question of lesional topography, as well as possible compensatory phenomena. We suggest that pure progressive amnesia results from selective damage to the ventral subhippocampal route into the hippocampal formation leading to impaired context-free memory. Spatial memory may remain intact because the dorsal parahippocampal route into the hippocampus remains functional. Pure progressive amnesia may contribute to a better understanding of the neural systems involved in declarative memory and provide a better understanding into the nature of the memory impairment that characterizes the initial stages of AD.

[Relapsing meningitis and confusion: limbic encephalitis revealing Hodgkin's disease]. / Méningite et confusion fébrile à rechute: encéphalite limbique révélant une maladie d'Hodgkin.

INTRODUCTION: An observation of limbic encephalitis associated with Hodgkin's disease is compared with rare cases of the literature. The clinical presentation was relapsing episodes of febrile cognitive disorders with confusion and meningitis, curable after treatment of Hodgkin's disease. Recent concepts on limbic encephalitis are discussed. CASE REPORT: A seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. During the year before his admission he had experienced four spontaneously regressive episodes of feverish confusion. Exploration of these episodes disclosed a paraneoplastic limbic encephalitis due to an underlying Hodgkin's disease. The treatment of Hodgkin's disease led to perfect recovery of cognitive function, so that the patient could drive his car. CONCLUSION: Lymphoproliferative disease, such as Hodgkin's disease, is a possible diagnosis in patients with limbic encephalitis. A dysimmune process underlying Hodgkin's disease might be operating in this association.

Rapid cognitive decline in Alzheimer's disease. Consensus paper.

The rate of cognitive decline in Alzheimer's disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different "a priori" definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.

[From perception to learning]. / De la perception à l'apprentissage.

In the field of perception, learning is formed by a distributed functional architecture of very specialized cortical areas. For example, capacities of learning in patients with visual deficits - hemianopia or visual agnosia - from cerebral lesions are limited by perceptual abilities. Moreover a visual deficit in link with abnormal perception may be associated with an alteration of representations in long term (semantic) memory. Furthermore, perception and memory traces rely on parallel processing. This has been recently demonstrated for human audition. Activation studies in normal subjects and psychophysical investigations in patients with focal hemispheric lesions have shown that auditory information relevant to sound recognition and that relevant to sound localisation are processed in parallel, anatomically distinct cortical networks, often referred to as the "What" and "Where" processing streams. Parallel processing may appear counterintuitive from the point of view of a unified perception of the auditory world, but there are advantages, such as rapidity of processing within a single stream, its adaptability in perceptual learning or facility of multisensory interactions. More generally, implicit learning mechanisms are responsible for the non-conscious acquisition of a great part of our knowledge about the world, using our sensitivity to the rules and regularities structuring our environment. Implicit learning is involved in cognitive development, in the generation of emotional processing and in the acquisition of natural language. Preserved implicit learning abilities have been shown in amnesic patients with paradigms like serial reaction time and artificial grammar learning tasks, confirming that implicit learning mechanisms are not sustained by the cognitive processes and the brain structures that are damaged in amnesia. In a clinical perspective, the assessment of implicit learning abilities in amnesic patients could be critical for building adapted neuropsychological rehabilitation programs.