[18F]DPA-714: Effect of co-medications, age, sex, BMI and TSPO polymorphism on the human plasma input function.

PURPOSE: We aimed to assess the effect of concomitant medication, age, sex, body mass index and 18-kDa translocator protein (TSPO) binding affinity status on the metabolism and plasma pharmacokinetics of [18F]DPA-714 and their influence on the plasma input function in a large cohort of 201 subjects who underwent brain and whole-body PET imaging to investigate the role of neuroinflammation in neurological diseases. METHODS: The non-metabolized fraction of [18F]DPA-714 was estimated in venous plasma of 138 patients and 63 healthy controls (HCs; including additional arterial sampling in 16 subjects) during the 90 min brain PET acquisition using a direct solid-phase extraction method. The mean fraction between 70 and 90 min post-injection ([18F]DPA-71470-90) and corresponding normalized plasma concentration (SUV70-90) were correlated with all factors using a multiple linear regression model. Differences between groups (arterial vs venous measurements; HCs vs patients; high- (HAB), mixed- (MAB) and low-affinity binders (LAB); subjects with vs without co-medications, females vs males were also assessed using the non-parametric Mann-Whitney or Kruskal-Wallis ANOVA tests. Finally, the impact of co-medications on the brain uptake of [18F]DPA-714 at equilibrium was investigated. RESULTS: As no significant differences were observed between arterial and venous [18F]DPA-71470-90 and SUV70-90, venous plasma was used for correlations. [18F]DPA-71470-90 was not significantly different between patients and HCS (59.7 ± 12.3% vs 60.2 ± 12.9%) despite high interindividual variability. However, 47 subjects exhibiting a huge increase or decrease of [18F]DPA-71470-90 (up to 88% or down to 23%) and SUV70-90 values (2-threefold) were found to receive co-medications identified as inhibitors or inducers of CYP3A4, known to catalyse [18F]DPA-714 metabolism. Comparison between cortex-to-plasma ratios using individual input function (VTIND) or population-based input function derived from untreated HCs (VTPBIF) indicated that non-considering the individual metabolism rate led to a bias of about 30% in VT values. Multiple linear regression model analysis of subjects free of these co-medications suggested significant correlations between [18F]DPA-71470-90 and age, BMI and sex while TSPO polymorphism did not influence the metabolism of the radiotracer. [18F]DPA-714 metabolism fell with age and BMI and was significantly faster in females than in males. Whole-body PET/CT exhibited a high uptake of the tracer in TSPO-rich organs (heart wall, spleen, kidneys…) and those involved in metabolism and excretion pathways (liver, gallbladder) in HAB and MAB with a strong decrease in LAB (-89% and -85%) resulting in tracer accumulation in plasma (4.5 and 3.3-fold increase). CONCLUSION: Any co-medication that inhibits or induces CYP3A4 as well as TSPO genetic status, age, BMI and sex mostly contribute to interindividual variations of the radiotracer metabolism and/or concentration that may affect the input function of [18F]DPA-714 and consequently its human brain and peripheral uptake. TRIAL REGISTRATION: INFLAPARK, NCT02319382, registered December 18, 2014, retrospectively registered; IMABIO 3, NCT01775696, registered January 25, 2013, retrospectively registered; INFLASEP, NCT02305264, registered December 2, 2014, retrospectively registered; EPI-TEP, EudraCT 2017-003381-27, registered September 24, 2018.

Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer's disease.

Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.

[Reconciliating neurology and psychiatry: The prototypical case of frontotemporal dementia]. / Rapprochement entre neurologie et psychiatrie : le cas prototypique de la dégénérescence frontotemporale.

Frontotemporal degeneration (FTD) in its behavioral variant (bvFTD) is probably one of the conditions that best illustrates the links between psychiatry and neurology. It is indeed admitted that between a third and half of patients with this condition, especially in early-onset forms, receive an initial diagnosis of psychiatric disorder (depression, schizophrenia, bipolar disorder) and are then referred to a psychiatric ward. BvFTD can thus be considered a neurological disorder with a psychiatric presentation. Among psychiatric symptoms reported in this disease, psychotic symptoms (hallucinations, delusions, especially of persecution), which have long been underestimated in bvFTD and are not part of the current diagnostic criteria, are present in about 20% of cases and may be inaugural. They are particularly common in the genetic forms related to a mutation in the C9orf72 gene (up to 50%), and to a lesser extent in the GRN gene (up to 25%). C9orf72 gene mutation is often associated with a family history of dementia or motor neuron disease but also of psychiatric disorders. It has also been described in sporadic presentation forms. Sometimes, the moderate degree of brain atrophy on MRI described in patients carrying this mutation may complicate the differential diagnosis with late-onset psychiatric diseases. In the present article, we underline the importance of considering that psychiatric - especially psychotic - symptoms are not rare in bvFTD, which should lead to a revision of the diagnostic criteria of this disease by taking greater account of this fact. We also propose a diagnostic chart, based on concerted evaluation by neurologists and psychiatrists for cases of atypical psychiatric symptoms (late-onset or pharmacoresistant troubles) leading to consider the possibility of a neurological disorder, in order to shed a new light on these difficult clinical situations. In the field of research, bvFTD may constitute a model to explore the neural basis of certain psychiatric disorders, and a possible molecular link between bvFTD and psychoses, which could eventually lead to new therapeutic approaches, has been recently suggested. Thus, bvFTD illustrates how the links between neurology and psychiatry are close and tend to evolve with the progress of scientific knowledge. It is necessary to strengthen collaboration between the two disciplines both to improve the care - diagnosis and management of these patients - and to promote the emergence of innovative clinical research.

The economic burden of urinary tract infections in women visiting general practices in France: a cross-sectional survey.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections. Despite this burden, there are few studies of the costs of UTIs. The objective of this study was to determine the costs of UTIs in women over 18 years of age who visit general practitioners in France. METHODS: The direct and indirect costs of clinical UTIs were estimated from societal, French National Health Insurance and patient perspectives. The study population was derived from a national cross-sectional survey entitled the Drug-Resistant Urinary Tract Infection (Druti). The Druti included every woman over 18 years of age who presented with symptoms of UTI and was conducted in France in 2012 and 2013 to estimate the annual incidence of UTIs due to antibiotic-resistant Enterobacteriaceae in women visiting general practitioners (GPs) for suspected UTIs. RESULTS: Of the 538 women included in Druti, 460 were followed over 8 weeks and included in the cost analysis. The mean age of the women was 46 years old. The median cost of care for one episode of a suspected UTI was €38, and the mean cost was €70. The annual societal cost was €58 million, and €29 million of this was reimbursed by the French National Health Insurance system. In 25 % of the cases, the suspected UTIs were associated with negative urine cultures. The societal cost of these suspected UTIs with negative urine cultures was €13.5 million. No significant difference was found between the costs of the UTIs due to antibiotic-resistant E. coli and those due to wild E. coli (p = 0.63). CONCLUSION: In the current context in which the care costs are continually increasing, the results of this study suggests that it is possible to decrease the cost of UTIs by reducing the costs of suspected UTIs and unnecessary treatments, as well as limiting the use of non-recommended tests.

Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients.

Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C(11)]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker.

Plasma DYRK1A as a novel risk factor for Alzheimer's disease.

To determine whether apparent involvement of DYRK1A in Alzheimer's disease (AD) pathology makes it a candidate plasma biomarker for diagnosis, we developed a method to quantify plasma DYRK1A by immunoblot in transgenic mouse models having different gene dosages of Dyrk1a, and, consequently, different relative protein expression. Then, we measured plasma DYRK1A levels in 26 patients with biologically confirmed AD and 25 controls (negative amyloid imaging available on 13). DYRK1A was detected in transgenic mouse brain and plasma samples, and relative levels of DYRK1A correlated with the gene copy number. In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001). Results were similar when we compared AD patients with the subgroup of controls confirmed by negative amyloid imaging. In a subgroup of patients with early AD (CDR=0.5), lower DYRK1A expression was confirmed. In contrast, no difference was found in levels of DYRK1B, the closest relative of DYRK1A, between AD patients and controls. Further, AD patients exhibited a positive correlation between plasma DYRK1A levels and cerebrospinal fluid tau and phosphorylated-tau proteins, but no correlation with amyloid-ß42 levels and Pittsburgh compound B cortical binding. DYRK1A levels detected in lymphoblastoid cell lines from AD patients were also lower when compared with cells from age-matched controls. These findings suggest that reduced DYRK1A expression might be a novel plasma risk factor for AD.

Alzheimer disease: from biomarkers to diagnosis.

The discovery of biomarkers, considered as surrogate markers of the underlying pathological changes, led an international work group (IWG) to propose a new conceptual framework for AD in 2007 Dubois et al. (2007). According to the IWG, AD is now defined as a dual clinico-biological entity that can be recognized in vivo, prior to the onset of the dementia syndrome, on the basis of: i) a specific core clinical phenotype comprised of an amnestic syndrome of the hippocampal type and ii) supportive evidence from biomarkers reflecting the location or the nature of Alzheimer-type changes. Therefore, AD is diagnosed with the same criteria throughout all symptomatic phases of the disease based on the biologically-based approach to diagnosis independent of clinical expression of disease severity. The definitions were further clarified in 2010 (Dubois et al., 2010). Although the new criteria are proposed for research purposes, we encourage expert centres with adequate resources to begin to use the proposed algorithm in order to move the field forward and facilitate translation into clinical practice.

Disease-specific adaptive immune biomarkers in Alzheimer's disease and related pathologies.

Identification of disease-specific diagnostic and prognostic biomarkers allowing for an early characterization and accurate clinical follow-up of Alzheimer's disease (AD) patients is a major clinical objective. Increasing evidences implicate both humoral and cellular adaptive immune responses in the pathophysiology of AD. Such disease-related B- and T-cell responses constitute a promising source of potential specific early biomarkers. Among them, levels of anti-Aß antibodies in the serum and/or cerebrospinal fluid of patients may correlate with AD progression, clinical presentation of the disease, and occurrence of associated pathologies related to cerebral amyloid angiopathy. In the same line, Aß-specific T cell responses and immune regulatory populations implicated in their modulation appear to play a role in the pathophysiology of AD and cerebral amyloid angiopathy. Further characterization of both autoantibodies and T cell responses specific for disease-related proteins, i.e. Aß and hyperphosphorylated Tau, will allow better deciphering their interest as early diagnostic and prognostic markers in AD. Biomarkers of adaptive immune responses specific for other pathological proteins may also apply to other neurological disorders associated with abnormal protein deposition.

Magnetic resonance imaging for diagnosis of early Alzheimer's disease.

A major challenge for neuroimaging is to contribute to the early diagnosis of Alzheimer's disease (AD). In particular, magnetic resonance imaging (MRI) allows detecting different types of structural and functional abnormalities at an early stage of the disease. Anatomical MRI is the most widely used technique and provides local and global measures of atrophy. The recent diagnostic criteria of "mild cognitive impairment due to AD" include hippocampal atrophy, which is considered a marker of neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in the hippocampus and throughout the whole brain. Recent modalities such as diffusion-tensor imaging and resting-state functional MRI provide additional measures that could contribute to the early diagnosis but require further validation.

[Markers of prodromal Alzheimer's disease]. / Les marqueurs de la maladie d'Alzheimer prodromale.

The diagnosis of Alzheimer's disease has long been considered a diagnosis of probability, as the definitive diagnosis can only be established by histopathological examination. However, the development of in-vivo biomarkers, considered a reflection of physiopathological processes, has changed our view of the disease. New criteria have recently been proposed that integrate such biomarkers as found in the cerebrospinal fluid (CSF) using new diagnostic tools such as magnetic resonance imaging (MRI), brain scintigraphy, FDG-positron emission tomography (PET) and PET amyloid ligand uptake studies. The value of these new criteria for the diagnosis of prodromal Alzheimer's disease and the prospect of disease-modifying drugs are also discussed.

[Orientation of patients referred by their general practionner to the public or private hospital sector in France: A prospective epidemiologic study]. / Orientation des patients par leur médecin généraliste vers les secteurs hospitaliers publics ou privés en France : étude épidémiologique prospective du réseau Sentinelles.

PURPOSE: In-patients characteristics generate cost differences between hospitals. In France, there are few data on the characteristics on the patients referred to hospitals by their general practitioners (GPs) and none on the predictors of referral to the public or for-profit hospitals. The aim of this study was to analyze those characteristics and the predictors of referral to the public or for-profit hospitals. METHODS: We collected, prospectively, the request for hospitalizations made by the GPs of the Sentinelles network in France, from 2007 to 2009. Patients' characteristics and also the reasons for that request were analyzed. A logistic regression was used to compare the population between local hospitals. RESULTS: Ten thousand seven hundred and eighteen statements were collected. The median age was 73 years. Patients were women in 51% of the cases, and only 14% of the hospitalizations had been planned. Hospitalization in the public sector was preferred for young children and the elderly (P<0.001). When compared to the patients referred to the private sector, patients addressed to the public sector were more often seen for emergencies (OR: 2.3 [2.0-2.8]), by a doctor different from their referring GP (OR: 1.7 [1.4-2.1]) and out of the GP's office. The reasons for hospital admission were different depending on the sector of hospitalization (P<0.001), patients addressed to the public sector hospitals presented with greater comorbidity or more complex diagnosis (for example: feeling ill, fainting or syncope and fever) or a greater disability (for example: stroke, neurological and psychiatric diseases). CONCLUSION: This study suggests that GPs send their patients to the public or for-profit hospitals according to criteria of severity, comorbidity and disability.

Physical medicine and rehabilitation multidisciplinary approach in a case of posterior cortical atrophy.

Posterior cortical atrophy (PCA) is a degenerative syndrome heralded by progressive visual and spatial disorders, while the memory and execution capacities remain preserved for a long time. We report the clinical case of a female patient who received a global Physical and Rehabilitation Medicine (PRM) therapy. Our objective is to highlight the interest of a multidisciplinary approach in PCA. A female patient, LO, 60 years old, presented with visual and spatial difficulties of progressive worsening, while global cognitive efficiency was preserved, signing PCA, with a loss of autonomy in daily life. A six-month multidisciplinary approach (speech therapy, occupational therapy, and physiotherapy) centered on her visual disturbances and associated to the reinforcement of her preserved abilities, as well as a rehabilitation program, was proposed. At the end of this period, LO was again able to read, find efficient exploratory strategies, use the underground, visit museums, have leisure activities, and carry out everyday life activities, which she had ended up abandoning. The specific therapeutic management allowed reaching functional objectives. Our hypothesis is that the absence of other cognitive disorders allowed this type of rehabilitation "contract". The neurodegenerative pathologies responsible for specific instrumental disabilities without global cognitive alteration, and particularly PCA, should be able to benefit from a specific, or even multidisciplinary PMR therapy approach.

[Beneficial effect of a cognitive behavioral and multidisciplinary program in Alzheimer Disease on spouse caregiver anxiety: French study ELMMA]. / Bénéfice d'un programme cognitivo-comportemental et pluridisciplinaire de prise en charge de la maladie d'Alzheimer sur l'anxiété du conjoint : étude française ELMMA.

INTRODUCTION: Over the last decade, several programs have been developed for caregivers of Alzheimer disease patients. In France however, studies exploring their effects are still scarce. We conducted a study to compare two different interventions: a structured multidisciplinary program versus a classical intervention designed for Alzheimer disease patients and their spouses. METHODS: Sixteen couples (Alzheimer's disease patient and spouse) residing in our administrative district participated in this monocentric study. For at least two years, these couples participated in a multidisciplinary program (n=8 couples) or received usual care (n=8 couples). The multidisciplinary program involved biannual consultations with a neurologist, a neuropsychologist and a psychologist, in addition to an annual meeting, stratified on the patient's MMSE score, for spouses). Usual care involved biannual consultations with the neurologist. The multidisciplinary program included a psychological intervention based on cognitive behavioral theories and centered on psycho-education, problem solving, adaptation strategies and on prevention of depression and anxiety. The spouses and the patients evaluated the 2-year follow-up during clinical interviews, completed by questionnaires. Sociodemographic data were noted for the patients and their spouses. Levels of depression and anxiety (Mini International Neuropsychiatric Inventory, Montgomery and Asberg Depression Scale, State-Trait Anxiety Inventory), perceived stress (Perceived Stress Scale) and care burden (Zarit Burden Inventory) were evaluated in spouses. Levels of cognitive impairment (Mini Mental State Examination), autonomy (Instrumental Activities of Daily Living), psychological state (Montgomery and Asberg Depression Scale, Covi Anxiety Scale), and behavioral symptoms frequency (Neuropsychiatric Inventory) were assessed in patients. RESULTS: The main significant result showed that the spouses' state of anxiety was lower among participants in the multidisciplinary program, compared with the classical neurological intervention. It also was found that the spouses and the patients who participated in this multidisciplinary program were less depressed. CONCLUSION: This study shows that a multidisciplinary structured intervention, with only two annual consultations and one annual meeting for spouses, can contribute to decrease significantly the spouses' state of anxiety. Further studies including a larger number of subjects should be conducted to confirm these findings.

Herpes zoster: Burden of disease in France.

This work provides estimates of HZ incidence and HZ-related hospitalization and mortality rates in France, where no immunization programme has been implemented. Herpes zoster data was obtained from the Sentinelles surveillance general practitioners (GPs) network, the PMSI Data processing centre for hospital discharges and from the French National Mortality Database (INSERM CépiDC). The yearly HZ incidence rate averaged 382 cases per 100,000 inhabitants (95% CI 364-405) and exponentially increased with age. The annual rates of hospitalizations and mortality due to HZ varied from 4.14±0.32 to 14.42±0.39 and from 0.11±0.03 to 0.29±0.04 per 100,000 inhabitants, respectively, depending on whether HZ was coded in a 'primary' or 'primary or associated' diagnosis. One or more factors of immunodepression occurred in 43.4% of hospitalized cases and in 21.6% HZ-related deaths.

[Semantic dementia associated with amyotrophic lateral sclerosis]. / Démence sémantique associée à une sclérose latérale amyotrophique.

The association semantic dementia-amyotrophic lateral sclerosis has been rarely reported in the literature. We report a case study of a patient with a severe prosopagnosia in relation with semantic dementia associated, 12 months later, with a motor neuron disease.

VBM anticipates the rate of progression of Alzheimer disease: a 3-year longitudinal study.

OBJECTIVE: To determine whether regional atrophy or neuropsychological factors can predict the rate of decline in patients with mild Alzheimer disease (AD). BACKGROUND: Despite important implications for planning the care and treatment strategy, few prognostic factors of severe AD progression are known. METHODS: Twenty-three patients with mild AD were followed up every 6 months over the course of 3 years. At baseline, patients with AD and 18 controls underwent a neuropsychological battery and a brain MRI. At the end of the 3 years, patients with AD were dichotomized into slow decliners (SLD) or fast decliners (FD) groups on the basis of their decline in Mini-Mental State Examination score over time. We compared baseline cognitive performance and imaging data using voxel-based morphometry (VBM). RESULTS: SLD and FD groups did not differ in age, gender, level of education, mean estimated duration of illness, and standard neuropsychological data at inclusion, except for the Attentional Battery of the Cambridge Neuropsychological Tests Automated Battery (speed processing in shifting condition). VBM comparison between SLD and FD groups demonstrated more gray matter tissue loss in the FD group in the medial occipitoparietal areas, especially in the precuneus, the lingual gyrus, the cuneus, and the surrounding cortex of the parieto-occipital sulcus bilaterally. CONCLUSION: Voxel-based morphometry analysis demonstrated that patients who will have a faster decline at 3 years already had a more extensive cortical atrophy than SLD patients, especially in the medial occipitoparietal areas, which was not yet detected by clinical and neuropsychological assessment.

[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.

Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study.

OBJECTIVE: To compare the power of tests assessing different cognitive domains for the identification of prodromal Alzheimer disease (AD) among patients with mild cognitive impairment (MCI). BACKGROUND: Given the early involvement of the medial temporal lobe, a precocious and specific pattern of memory disorders might be expected for the identification of prodromal AD. METHODS: A total of 251 patients with MCI were tested at baseline by a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for verbal episodic memory; the Benton Visual Retention Test for visual memory; the Deno 100 and verbal fluency for language; a serial digit learning test and the double task of Baddeley for working memory; Wechsler Adult Intelligence Scale (WAIS) similarities for conceptual elaboration; and the Stroop test, the Trail Making test, and the WAIS digit symbol test for executive functions. The patients were followed at 6-month intervals for up to 3 years in order to identify those who converted to AD vs those who remained stable over time. Statistical analyses were based on receiver operating characteristic curve and Cox proportional hazards models. RESULTS: A total of 59 subjects converted to AD dementia. The most sensitive and specific test for diagnosis of prodromal AD was the FCSRT. Significant cutoff for the diagnosis was 17/48 for free recall, 40/48 for total recall, and below 71% for index of sensitivity of cueing (% of efficacy of semantic cues for retrieval). CONCLUSIONS: The amnestic syndrome of the medial temporal type, defined by the Free and Cued Selective Recall Reminding Test, is able to distinguish patients at an early stage of Alzheimer disease from mild cognitive impairment non-converters.

Method of estimating time scales of atmospheric piston and its application at Dome C (Antarctica).

Temporal fluctuations of the atmospheric piston are critical for interferometers as they determine their sensitivity. We characterize an instrumental setup, termed the piston scope, that aims at measuring the atmospheric time constant, tau(0), through the image motion in the focal plane of a Fizeau interferometer. High-resolution piston scope measurements have been obtained at the observatory of Paranal, Chile in April 2006. The derived atmospheric parameters are shown to be consistent with data from the astronomical site monitor, provided that the atmospheric turbulence is displaced along a single direction. The piston scope measurements of lower temporal and spatial resolution were recorded for what is believed to be the first time in February 2005 at the Antarctic site of Dome C. Their reanalysis in terms of the new data calibration sharpens the conclusions of a first qualitative examination [Appl. Opt. 45, 5709 (2006)].