Usefulness of PET With [18F]LBT-999 for the Evaluation of Presynaptic Dopaminergic Neuronal Loss in a Clinical Environment.

Purpose: The density of the neuronal dopamine transporter (DAT) is directly correlated with the presynaptic dopaminergic system injury. In a first study, we evaluated the brain distribution and kinetics of [18F]LBT-999, a DAT PET radioligand, in a group of eight healthy subjects. Taking into account the results obtained in healthy volunteers, we wanted to evaluate whether the loss of presynaptic striatal dopaminergic fibers could be estimated, under routine clinical conditions, using [18F]LBT-999 and a short PET acquisition. Materials and methods: Six patients with Parkinson's disease (PD) were compared with eight controls. Eighty-nine minutes of dynamic PET following an intravenous injection of [18F]LBT-999 were acquired. Using regions of interest for striatal nuclei, substantia nigra (SN), cerebellum, and occipital cortex, defined over each T1 3D MRI, time-activity curves (TACs) were obtained. From TACs, binding potential (BPND) using the simplified reference tissue model and distribution volume ratios (DVRs) using Logan graphical analysis were calculated. Ratios obtained for a 10-min image, acquired between 30 and 40 min post-injection, were also calculated. Cerebellum activity was used as non-specific reference region. Results: In PD patients and as expected, striatal uptake was lower than in controls which is confirmed by BPND, DVR, and ratios calculated for both striatal nuclei and SN, significantly inferior in PD patients compared with controls (p < 0.001). Conclusions: PET with [18F]LBT-999 could be an alternative to assess dopaminergic presynaptic injury in a clinical environment using a single 10 min acquisition.

Isolated parkinsonism is an atypical presentation of GRN and C9orf72 gene mutations.

INTRODUCTION: A phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It still remains controversial if this association is fortuitous or not, and which clinical clues could reliably suggest a genetic FTD etiology in IPD patients. This study aims to describe the clinical characteristics of FTD mutation carriers presenting with IPD phenotype, provide neuropathological evidence of the mutation's causality, and specifically address their "red flags" according to current IPD criteria. METHODS: Seven GRN and C9orf72 carriers with isolated parkinsonism at onset, and three patients from the literature were included in this study. To allow better delineation of their phenotype, the presence of supportive, exclusion and "red flag" features from MDS criteria were analyzed for each case. RESULTS: Amongst the ten patients (5 GRN, 5 C9orf72), seven fulfilled probable IPD criteria during all the disease course, while behavioral/language or motoneuron dysfunctions occurred later in three. Disease duration was longer and dopa-responsiveness was more sustained in C9orf72 than in GRN carriers. Subtle motor features, cognitive/behavioral changes, family history of dementia/ALS were suggestive clues for a genetic diagnosis. Importantly, neuropathological examination in one patient revealed typical TDP-43-inclusions without alpha-synucleinopathy, thus demonstrating the causal link between FTD mutations, TDP-43-pathology and PD phenotype. CONCLUSION: We showed that, altogether, family history of early-onset dementia/ALS, the presence of cognitive/behavioral dysfunction and subtle motor characteristics are atypical features frequently present in the parkinsonian presentations of GRN and C9orf72 mutations.

Amyloid PET Positivity in Different Primary Progressive Aphasia Phenotypes.

PURPOSE: Primary progressive aphasia (PPA) is a neurological syndrome in which language functions become progressively impaired with relative sparing of memory and other instrumental functions. The pathologic causes of PPA are heterogeneous, but studies suggest that logopenic PPA (LPA) is underpinned by Alzheimer disease (AD) pathology in a high proportion of cases. The purposes of this descriptive and retrospective study were to characterize F-florbetapir PET imaging in a group of patients with a clinical syndrome of PPA, to determine the value of clinical characterization based on language phenotype in predicting the underlying pathology of PPA with F-florbetapir, and to quantify amyloid load in PPA subjects classified as "positive" F-florbetapir scans. Then, we compare the quantification and distribution of F-florbetapir uptake with those of typical, predominantly amnestic AD patients. METHODS: We conducted a PET study with F-florbetapir in a cohort of 12 right-handed patients diagnosed with PPA: 3 patients with semantic-variant PPA, 5 with nonfluent PPA, 1 with LPA, and 3 unclassifiable patients. We evaluated amyloid deposition between APP groups and 11 patients with typical amnestic AD. RESULTS: Among the 12 patients with PPA syndrome, 8 (66.7%) were considered as amyloid positive. One of the 3 patients with semantic-variant PPA was F-florbetapir positive. In contrast, 4 of the 5 nonfluent-variant PPA, 2 of the 3 unclassifiable cases and the single patient with LPA were F-florbetapir positive. A significantly higher F-florbetapir uptake was observed in PPA F-florbetapir-positive patients compared with typical AD patients. This difference was observed in all regions of interest, except in posterior cingulate and temporal cortex. CONCLUSIONS: These results suggest that F-florbetapir PET may be useful in a routine clinical procedure to improve the reliability of identifying AD pathology in patients with PPA syndrome, with different clinical subtypes of the PPA syndrome.

Hedonic Assessment of Odors: A Comparison of Two Sensory Scales for Use with Alzheimer's Disease Patients and Elderly Individuals.

BACKGROUND: Several clinical studies concerning the olfactory function of patients with cognitive impairment have used sensory scales to investigate hedonic perception. However, no study has focused on the choice of the most appropriate sensory hedonic scale for the individuals with neurodegenerative disorders or other psychiatric diseases involving cognitive deficits. OBJECTIVE: The aim of this study was to investigate the ability of patients with Alzheimer's disease (AD) to use two hedonic scales (category scale and linear scale) and compare their discriminatory capacity, repeatability, and ease of use. This should allow us to identify the most appropriate hedonic scale for patients with AD. METHODS: We recruited 18 patients with mild to moderate AD, and 20 healthy volunteers matched for gender, age, smoking status, and educational level. The participants underwent a clinical assessment and hedonic evaluation of three odorants (pleasant, unpleasant, and neutral), using a five-point category scale and a 10-cm linear scale with a marked mid-point. RESULTS: AD patients were able to use hedonic scales as well as paired healthy elderly subjects. The linear scale performed slightly better in terms of ease of use for both patients and healthy controls and discriminatory capacity for AD patients. The results for AD patients and controls with both scales were repeatable. CONCLUSION: The linear scale may be more appropriate for AD patients pending further studies involving a larger population of patients, using several odorants.

[Transient epileptic amnesia]. / L'amnésie épileptique transitoire (AET).

Transient epileptic amnesia (TEA) is a sub-type of mesial temporal lobe epilepsy, with amnesic seizures. TEA is characterized by recurrent episodes of amnesia. Diagnostic criteria are available for TEA, and these memory disturbances should not be misdiagnosed with transient global amnesia. The neuropsychological evaluation is normal, however, autobiographical memory impairment is present in 70% of the cases and accelerated long term forgetting in 44%. When a patient complains of memory disturbances, especially autobiographical memory, TEA must be considered especially if there was an amnesic episode and symptoms that suggest temporal epilepsia. Video electroencephalography monitoring of sleep is a precious diagnostic tool, as epileptiform activities are found during sleep in 83% cases. TEA is pharmaco-sensitive, with full treatment response in 73 to 96% of the cases.

A case of Capgras syndrome with one's own reflected image in a mirror.

We report the case of a 78-year-old patient admitted to the hospital for behavioral and psychological disorders consisting in impressions of presence of a stranger located behind the bathroom mirror, who strikingly shared the patient's appearance but was considered a different person, yet. We discuss how this case can be interpreted as an atypical Capgras syndrome for his mirror image and how it suggests an adjustment of the classical dual-route model that sustains face recognition between covert (or affective) and overt neural pathways.

Functional Outcome of Hemorrhagic Transformation after Thrombolysis for Ischemic Stroke: A Prospective Study.

BACKGROUND/AIMS: Hemorrhagic transformation (HT) is usually taken into account when symptomatic, but the role of asymptomatic HT is not well known. The aim of our study was to evaluate the link between HT after thrombolysis for ischemic stroke and functional outcome at 3 months, with particular emphasis on asymptomatic HT. METHODS: Our study was performed prospectively between June 2012 and June 2013 in the Stroke Unit of the University Hospital Center of Tours (France). All patients treated with intravenous thrombolysis were consecutively included. HT was classified on susceptibility-weighted imaging (SWI) with 3-tesla MRI at 7 ± 3 days after treatment. We evaluated functional outcome at 3 months using the modified Rankin Scale (mRS). Dependency was defined as an mRS score of ≥ 3. RESULTS: After 1 year, 128 patients had received thrombolytic therapy for ischemic stroke, of whom 90 patients underwent both 3-tesla MRI and SWI at day 7. Fifty-two had HT, including 8 symptomatic cases. At 3 months, 68% of those patients were dependent compared to 31% of patients without HT [OR 4.6 (1.9-11.4), p = 0.001]. In asymptomatic HT, the rate was 62% [OR 3.5 (1.4-8.9), p = 0.007], but did not reach significance after adjustment for stroke severity. DISCUSSION: Our study found no statistically significant effect of HT on outcome after adjustment for initial stroke severity. However, the innocuousness of HT is not certain, and only few studies have already highlighted the increased risk of dependency. Using 3-tesla MRI with SWI allows us to increase the detection rate of small hemorrhage. CONCLUSION: HT after thrombolysis is very frequent on SWI, but the initial stroke severity is an important predictor to assess the role of HT for patient outcome.

Quality of Life After Off-Label Thrombolysis for Ischemic Stroke in Elderly Patients.

INTRODUCTION: The use of intravenous thrombolysis with alteplase for ischemic stroke in Europe is restricted to subjects aged <80 years. Recent studies have reported the efficacy and safety of alteplase in older patients. However, data concerning the quality of life (QOL) of these elderly subjects are sparse. OBJECTIVES: The aim of this study was to compare the QOL of patients aged ≥80 years with that of patients aged <80 years at 3 months after thrombolysis. METHOD: This was a prospective study comprising French-speaking patients aged >18 years treated using thrombolytic therapy for ischemic stroke at the Hospital of Tours (Tours, France) between June 2012 and January 2013. QOL was assessed using the Stroke Impact Scale (SIS). The presence of mood disorders or cognitive impairments was also assessed. RESULTS: QOL was evaluated for 62 subjects among the 83 enrolled patients who received thrombolytic treatment; 21 patients were aged >80 years. Concerning scores on the SIS, using a multivariate analysis, only the memory and thinking score was significantly and negatively associated with the elderly population [odds ratio (OR) 0.036, 95% confidence interval (CI) 0.004-0.339; p = 0.004]. No significant difference was observed among all the other QOL scores. Neurological recovery and functional status did not differ between the two groups. CONCLUSION: QOL after intravenous thrombolysis in the elderly population was comparable to that of younger subjects. Despite its small sample size, this study showed promising results in favor of intravenous thrombolysis in the elderly population and highlighted the importance of systematic screening for post-stroke cognitive impairment, particularly in this population.

Precuneus and Cingulate Cortex Atrophy and Hypometabolism in Patients with Alzheimer's Disease and Mild Cognitive Impairment: MRI and (18)F-FDG PET Quantitative Analysis Using FreeSurfer.

OBJECTIVE: The objective of this study was to compare glucose metabolism and atrophy, in the precuneus and cingulate cortex, in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), using FreeSurfer. METHODS: 47 individuals (17 patients with AD, 17 patients with amnestic MCI, and 13 healthy controls (HC)) were included. MRI and PET images using (18)F-FDG (mean injected dose of 185 MBq) were acquired and analyzed using FreeSurfer to define regions of interest in the hippocampus, amygdala, precuneus, and anterior and posterior cingulate cortex. Regional volumes were generated. PET images were registered to the T1-weighted MRI images and regional uptake normalized by cerebellum uptake (SUVr) was measured. RESULTS: Mean posterior cingulate volume was reduced in MCI and AD. SUVr were different between the three groups: mean precuneus SUVr was 1.02 for AD, 1.09 for MCI, and 1.26 for controls (p < 0.05); mean posterior cingulate SUVr was 0.96, 1.06, and 1.22 for AD, MCI, and controls, respectively (p < 0.05). CONCLUSION: We found graduated hypometabolism in the posterior cingulate cortex and the precuneus in prodromal AD (MCI) and AD, whereas atrophy was not significant. This suggests that the use of (18)F-FDG in these two regions could be a neurodegenerative biomarker.

Taste identification used as a potential discriminative test among depression and Alzheimer׳s disease in elderly: A pilot study.

Major Depression and Alzheimer׳s disease (AD) are two diseases in the elderly characterized by an overlap of early symptoms including memory and emotional disorders. The identification of specific markers would facilitate their diagnosis. The aim of this study was to identify such markers by investigating gustatory function in depressed and AD patients. We included 20 patients with unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD and 24 healthy individuals. We investigated the cognitive profile (depression, global cognitive efficiency and social/physical anhedonia) and gustatory function (ability to identify four basic tastes and to judge their intensity and hedonic value) in all participants. We found that AD patients performed worse than healthy participants in the taste identification test (for the analysis of all tastants together); however, this was not the case for depressed patients. We found no significant differences among the three groups in their ability to evaluate the intensity and hedonic value of the four tastes. Overall, our findings suggest that a taste identification test may be useful to distinguish AD and healthy controls but further investigation is required to conclude whether such a test can differentiate AD and depressed patients.

Sinking skin flap syndrome (or Syndrome of the trephined): A review.

BACKGROUND: Bone defects of the skull are observed in various pathological conditions, including head trauma and conditions requiring surgery of the skull. Independent of the consequences of the original aetiology that necessitated the craniectomy, the bone defect alone may be the cause of the symptoms, called 'trephined syndrome' or 'sinking skin flap syndrome'. Despite the early recognition of neurological symptoms directly linked to craniectomy, the description of this syndrome has often relied on a small series or single clinical case reports. OBJECTIVES: To list the previously reported symptoms of SSFS. DATA SOURCES: We selected the references for this review by searching PubMed, focusing on articles published prior to June 2013 and using references from relevant articles. STUDY ELIGIBILITY CRITERIA: We used the following search terms: 'trephined syndrome', 'syndrome of the trephined', 'Sinking skin flap', and 'sinking skin flap syndrome'. There were no language restrictions. The final reference list was generated on the basis of its relevance to the topics covered in this review. CONCLUSIONS: Clinicians need to be aware of sinking skin flap syndrome and to look for abnormal neurological developments in patients with craniectomy in order to avoid unnecessary testing and to prevent its occurrence. Accordingly, cranioplasty can be undertaken as soon as necessary.

The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using (18)F-AV45: Is Amyloid the Principal Actor in the Disease?

BACKGROUND: Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimer's disease (AD). The aim of this study was to compare the amyloid load with (18)F-AV45 positron emission tomography (PET) between PCA and AD subjects. METHODS: We performed (18)F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. RESULTS: The global and regional (18)F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global (18)F-AV45 uptake and CSF biomarkers or between regional (18)F-AV45 uptake and cognitive and affective symptoms. CONCLUSION: This (18)F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical (18)F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution.

Long-term odor recognition memory in unipolar major depression and Alzheimer׳s disease.

Major depression and Alzheimer׳s disease (AD) are often observed in the elderly. The identification of specific markers for these diseases could improve their screening. The aim of this study was to investigate long-term odor recognition memory in depressed and AD patients, with a view to identifying olfactory markers of these diseases. We included 20 patients with unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD and 24 healthy subjects. We investigated the cognitive profile and olfactory memory capacities (ability to recognize familiar and unfamiliar odors) of these subjects. Olfactory memory test results showed that AD and depressed patients were characterized by significantly less correct responses and more wrong responses than healthy controls. Detection index did not differ significantly between patients with major depression and those with AD when the results were analyzed for all odors. However, MDE patients displayed an impairment of olfactory memory for both familiar and unfamiliar odors, whereas AD subjects were impaired only in the recognition of unfamiliar odors, with respect to healthy subjects. If preservation of olfactory memory for familiar stimuli in patients with mild to moderate AD is confirmed, this test could be used in clinical practice as a complementary tool for diagnosis.

[Perception of taste and smell in normal and pathological aging: an update]. / Perception du goût et des odeurs au cours du vieillissement normal et pathologique : mise au point.

The physiological and pathological aging on sense organs is widely studied in the visual and hearing modalities. By contrast, taste and smell changes are widely overlooked. These symptoms are rarely evoked in the elderly and often neglected in clinical practice. Studies in this population are rare and show contradictory results. In this update, we describe the perception of taste and smell in aging. In a first part, we present studies about the aging of smell and taste senses. While taste is remarkably spared during aging, olfaction decreases dramatically since 5th decade of life, frequently resulting in anosmia after 90 years. Numerous causes are evoked: acute conditions (mouth health, medications…) and chronic diseases frequently observed during aging (Alzheimer or Parkinson's diseases) may be responsible of such decline. In the last part, we approach the consequences on geriatric practice, as regards the nutrition of old subjects, including a cognitive approach regarding to perceptual functions and environmental determinants of nutrition. Taste and olfaction disorders should be considered as a geriatric syndrome that geriatricians have to be aware in clinical practice.

Using the Brief Assessment of Cognition in Schizophrenia (BACS) to assess cognitive impairment in older patients with schizophrenia and bipolar disorder.

OBJECTIVES: A growing body of evidence suggests that impairment in cognitive functioning is an important clinical feature of both schizophrenia and bipolar disorder, and that these cognitive alterations worsen with age. Although cognitive assessments are increasingly becoming a part of research and clinical practice in schizophrenia, a standardized and easily administered test battery for elderly patients with bipolar disorder is still lacking. The Brief Assessment of Cognition in Schizophrenia (BACS) captures those domains of cognition that are the most severely affected in patients with schizophrenia and the most strongly correlated with functional outcome. The primary aim of our study was to investigate the clinical usefulness of the BACS in assessing cognitive functioning in elderly euthymic patients with bipolar disorder, and to compare their cognitive profile to that of elderly patients with schizophrenia. METHODS: Elderly euthymic patients with bipolar disorder or schizophrenia were assessed using the BACS and a standard cognitive test battery. RESULTS: Fifty-seven elderly patients (aged 60 years and older) with bipolar disorder (n = 42) or schizophrenia (n = 15) were invited to participate. All of the patients were assessed by the BACS as being cognitively impaired. The patients with bipolar disorder scored significantly higher on the global scale and the verbal memory and attention sub-scores of the BACS than the patients with schizophrenia. DISCUSSION: The BACS appears to be a feasible and informative cognitive assessment tool for elderly patients with bipolar disorder. We believe that these preliminary results merit further investigation.