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1.  Cognitive and affective theory of mind in dementia with Lewy bodies and Alzheimer’s disease 
Background
Theory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have been published. The aim of our study was to assess ToM in patients with DLB and to search for neural correlates of potential deficits.
Methods
Thirty-three patients with DLB (DLB group) and 15 patients with Alzheimer’s disease (AD group), all in the early stage of the disease, as well as 16 healthy elderly control subjects (HC group), were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition (FPR) test, the Reading the Mind in the Eyes (RME) test and Ekman’s Facial Emotion Recognition test to assess cognitive and affective components of ToM. Patients underwent cerebral 3-T magnetic resonance imaging, and atrophy of grey matter was analysed using voxel-based morphometry. We performed a one-sample t test to investigate the correlation between each ToM score and grey matter volume and a two-sample t test to compare patients with DLB impaired with those non-impaired for each test.
Results
The DLB group performed significantly worse than the HC group on the FPR test (P = 0.033) and the RME test (P = 0.015). There was no significant difference between the AD group and the HC group or between the DLB group and the AD group. Some brain regions were associated with ToM impairments. The prefrontal cortex, with the inferior frontal cortex and the orbitofrontal cortex, was the main region, but we also found correlations with the temporoparietal junction, the precuneus, the fusiform gyrus and the insula.
Conclusions
This study is the first one to show early impairments of ToM in DLB. The two cognitive and affective components both appear to be affected in this disease. Among patients with ToM difficulties, we found atrophy in brain regions classically involved in ToM, which reinforces the neuronal network of ToM. Further studies are now needed to better understand the neural basis of such impairment.
Electronic supplementary material
The online version of this article (doi:10.1186/s13195-016-0179-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s13195-016-0179-9
PMCID: PMC4793654  PMID: 26979460
Theory of mind; Dementia with Lewy bodies; Alzheimer’s disease; Brain volume; Neural correlates
2.  Visible‐Light‐Driven Hydrogen Evolution Using Planarized Conjugated Polymer Photocatalysts 
Abstract
Linear poly(p‐phenylene)s are modestly active UV photocatalysts for hydrogen production in the presence of a sacrificial electron donor. Introduction of planarized fluorene, carbazole, dibenzo[b,d]thiophene or dibenzo[b,d]thiophene sulfone units greatly enhances the H2 evolution rate. The most active dibenzo[b,d]thiophene sulfone co‐polymer has a UV photocatalytic activity that rivals TiO2, but is much more active under visible light. The dibenzo[b,d]thiophene sulfone co‐polymer has an apparent quantum yield of 2.3 % at 420 nm, as compared to 0.1 % for platinized commercial pristine carbon nitride.
doi:10.1002/anie.201510542
PMCID: PMC4755226  PMID: 26696450
conjugated polymer; extended conjugation; photocatalysis; planarization; water splitting
3.  Joint Experimental and Computational 17O and 1H Solid State NMR Study of Ba2In2O4(OH)2 Structure and Dynamics 
Chemistry of Materials  2015;27(11):3861-3873.
A structural characterization of the hydrated form of the brownmillerite-type phase Ba2In2O5, Ba2In2O4(OH)2, is reported using experimental multinuclear NMR spectroscopy and density functional theory (DFT) energy and GIPAW NMR calculations. When the oxygen ions from H2O fill the inherent O vacancies of the brownmillerite structure, one of the water protons remains in the same layer (O3) while the second proton is located in the neighboring layer (O2) in sites with partial occupancies, as previously demonstrated by Jayaraman et al. (Solid State Ionics2004, 170, 25−32) using X-ray and neutron studies. Calculations of possible proton arrangements within the partially occupied layer of Ba2In2O4(OH)2 yield a set of low energy structures; GIPAW NMR calculations on these configurations yield 1H and 17O chemical shifts and peak intensity ratios, which are then used to help assign the experimental MAS NMR spectra. Three distinct 1H resonances in a 2:1:1 ratio are obtained experimentally, the most intense resonance being assigned to the proton in the O3 layer. The two weaker signals are due to O2 layer protons, one set hydrogen bonding to the O3 layer and the other hydrogen bonding alternately toward the O3 and O1 layers. 1H magnetization exchange experiments reveal that all three resonances originate from protons in the same crystallographic phase, the protons exchanging with each other above approximately 150 °C. Three distinct types of oxygen atoms are evident from the DFT GIPAW calculations bare oxygens (O), oxygens directly bonded to a proton (H-donor O), and oxygen ions that are hydrogen bonded to a proton (H-acceptor O). The 17O calculated shifts and quadrupolar parameters are used to assign the experimental spectra, the assignments being confirmed by 1H–17O double resonance experiments.
doi:10.1021/acs.chemmater.5b00328
PMCID: PMC4547502  PMID: 26321789
4.  Characterization of the Dynamics in the Protonic Conductor CsH2PO4 by 17O Solid-State NMR Spectroscopy and First-Principles Calculations: Correlating Phosphate and Protonic Motion 
17O NMR spectroscopy combined with first-principles calculations was employed to understand the local structure and dynamics of the phosphate ions and protons in the paraelectric phase of the proton conductor CsH2PO4. For the room-temperature structure, the results confirm that one proton (H1) is localized in an asymmetric H-bond (between O1 donor and O2 acceptor oxygen atoms), whereas the H2 proton undergoes rapid exchange between two sites in a hydrogen bond with a symmetric double potential well at a rate ≥107 Hz. Variable-temperature 17O NMR spectra recorded from 22 to 214 °C were interpreted by considering different models for the rotation of the phosphate anions. At least two distinct rate constants for rotations about four pseudo C3 axes of the phosphate ion were required in order to achieve good agreement with the experimental data. An activation energy of 0.21 ± 0.06 eV was observed for rotation about the P–O1 axis, with a higher activation energy of 0.50 ± 0.07 eV being obtained for rotation about the P–O2, P–O3d, and P–O3a axes, with the superscripts denoting, respectively, dynamic donor and acceptor oxygen atoms of the H-bond. The higher activation energy of the second process is most likely associated with the cost of breaking an O1–H1 bond. The activation energy of this process is slightly lower than that obtained from the 1H exchange process (0.70 ± 0.07 eV) (Kim, G.; Blanc, F.; Hu, Y.-Y.; Grey, C. P. J. Phys. Chem. C2013, 117, 6504−6515) associated with the translational motion of the protons. The relationship between proton jumps and phosphate rotation was analyzed in detail by considering uncorrelated motion, motion of individual PO4 ions and the four connected/H-bonded protons, and concerted motions of adjacent phosphate units, mediated by proton hops. We conclude that, while phosphate rotations aid proton motion, not all phosphate rotations result in proton jumps.
doi:10.1021/jacs.5b00280
PMCID: PMC4519985  PMID: 25732257
5.  Different Temporal Patterns of Specific and General Autobiographical Memories across the Lifespan in Alzheimer's Disease 
Behavioural Neurology  2015;2015:963460.
We compared specific (i.e., associated with a unique time and space) and general (i.e., extended or repeated events) autobiographical memories (AbM) in Alzheimer's disease (AD). The comparison aims at investigating the relationship between these two components of AbM across the lifespan and the volume of cerebral regions of interest within the temporal lobe. We hypothesized that the ability to elicit specific memories would correlate with hippocampal volume, whereas evoking general memories would be related to lateral temporal lobe. AbM was assessed using the modified Crovitz test in 18 patients with early AD and 18 matched controls. The proportions of total memories—supposed to reflect the ability to produce general memories—and specific memories retrieved were compared between AD patients and controls. Correlations to MRI volumes of temporal cortex were tested. We found different temporal patterns for specific and general memories in AD patients, with (i) relatively spared general memories, according to a temporal gradient that preserved remote memories, predominantly associated with right lateral temporal cortex volume. (ii) Conversely, the retrieval of specific AbMs was impaired for all life periods and correlated with bilateral hippocampal volumes. Our results highlight a shift from an initially episodic to a semantic nature of AbMs during AD, where the abstracted form of memories remains.
doi:10.1155/2015/963460
PMCID: PMC4484842  PMID: 26175549
6.  Identification of different oxygen species in oxide nanostructures with 17O solid-state NMR spectroscopy 
Science Advances  2015;1(1):e1400133.
Nanostructured oxides find multiple uses in a diverse range of applications including catalysis, energy storage, and environmental management, their higher surface areas, and, in some cases, electronic properties resulting in different physical properties from their bulk counterparts. Developing structure-property relations for these materials requires a determination of surface and subsurface structure. Although microscopy plays a critical role owing to the fact that the volumes sampled by such techniques may not be representative of the whole sample, complementary characterization methods are urgently required. We develop a simple nuclear magnetic resonance (NMR) strategy to detect the first few layers of a nanomaterial, demonstrating the approach with technologically relevant ceria nanoparticles. We show that the 17O resonances arising from the first to third surface layer oxygen ions, hydroxyl sites, and oxygen species near vacancies can be distinguished from the oxygen ions in the bulk, with higher-frequency 17O chemical shifts being observed for the lower coordinated surface sites. H217O can be used to selectively enrich surface sites, allowing only these particular active sites to be monitored in a chemical process. 17O NMR spectra of thermally treated nanosized ceria clearly show how different oxygen species interconvert at elevated temperature. Density functional theory calculations confirm the assignments and reveal a strong dependence of chemical shift on the nature of the surface. These results open up new strategies for characterizing nanostructured oxides and their applications.
doi:10.1126/sciadv.1400133
PMCID: PMC4644084  PMID: 26601133
7.  Neural correlates of visual hallucinations in dementia with Lewy bodies 
Introduction
The aim of this study was to investigate the association between visual hallucinations in dementia with Lewy bodies (DLB) and brain perfusion using single-photon emission computed tomography.
Methods
We retrospectively included 66 patients with DLB, 36 of whom were having visual hallucinations (DLB-hallu) and 30 of whom were not (DLB-c). We assessed visual hallucination severity on a 3-point scale of increasing severity: illusions, simple visual hallucinations and complex visual hallucinations. We performed voxel-level comparisons between the two groups and assessed correlations between perfusion and visual hallucinations severity.
Results
We found a significant decrease in perfusion in the left anterior cingulate cortex, the left orbitofrontal cortex and the left cuneus in the DLB-hallu group compared with the DLB-c group. We also found a significant correlation between decreased bilateral anterior cingulate cortex, left orbitofrontal cortex, right parahippocampal gyrus, right inferior temporal cortex and left cuneus perfusion with the severity of hallucinations.
Conclusions
Visual hallucinations seem to be associated with the impairment of anterior and posterior regions (secondary visual areas, orbitofrontal cortex and anterior cingulate cortex) involved in a top-down and bottom-up mechanism, respectively. Furthermore, involvement of the bilateral anterior cingulate cortex and right parahippocampal gyrus seems to lead to more complex hallucinations.
doi:10.1186/s13195-014-0091-0
PMCID: PMC4339752  PMID: 25717349
8.  Impaired emotional autobiographical memory associated with right amygdalar-hippocampal atrophy in Alzheimer’s disease patients 
We studied the influence of emotions on autobiographical memory (AbM) in patients with Alzheimer’s disease (AD), characteristically triggering atrophy in the hippocampus and the amygdala, two crucial structures sustaining memory and emotional processing. Our first aim was to analyze the influence of emotion on AbM in AD patients, on both the proportion and the specificity of emotional memories. Additionally, we sought to determine the relationship of emotional AbM to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18 age-matched healthy controls were included. We obtained 30 autobiographical memories per participant using the modified Crovitz test (MCT). Analyses were performed on global scores, rates and specificity scores of the emotional vs. neutral categories of memories. Amygdalar-hippocampal volumes were extracted from 3D T1-weighted MRI scans and tested for correlations with behavioral data. Overall, AD patients displayed a deficit in emotional AbMs as they elicited less emotional memories than the controls, however, the specificity of those memories was preserved. The deficit likely implied retrieval or storage as it was extended in time and without reminiscence bump effect. Global scores and rates of emotional memories, but not the specificity scores, were correlated to right amygdalar and hippocampal volumes, indicating that atrophy in these structures has a central role in the deficit observed. Conversely, emotional memories were more specific than neutral memories in both groups, reflecting an enhancement effect of emotion that could be supported by other brain regions that are spared during the early stages of the disease.
doi:10.3389/fnagi.2015.00021
PMCID: PMC4360763  PMID: 25852541
emotion; autobiographical memory; Alzheimer’s disease; amygdala; hippocampus
9.  Right Anterior Insula: Core Region of Hallucinations in Cognitive Neurodegenerative Diseases 
PLoS ONE  2014;9(12):e114774.
Objectives
We investigated the neural basis of hallucinations Alzheimer's disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.
Methods
AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. “Core regions” (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.
Results
Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).
Conclusion
Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.
doi:10.1371/journal.pone.0114774
PMCID: PMC4257732  PMID: 25479196
10.  Acetyltransferases (HATs) as Targets for Neurological Therapeutics 
Neurotherapeutics  2013;10(4):568-588.
The acetylation of histone and non-histone proteins controls a great deal of cellular functions, thereby affecting the entire organism, including the brain. Acetylation modifications are mediated through histone acetyltransferases (HAT) and deacetylases (HDAC), and the balance of these enzymes regulates neuronal homeostasis, maintaining the pre-existing acetyl marks responsible for the global chromatin structure, as well as regulating specific dynamic acetyl marks that respond to changes and facilitate neurons to encode and strengthen long-term events in the brain circuitry (e.g., memory formation). Unfortunately, the dysfunction of these finely-tuned regulations might lead to pathological conditions, and the deregulation of the HAT/HDAC balance has been implicated in neurological disorders. During the last decade, research has focused on HDAC inhibitors that induce a histone hyperacetylated state to compensate acetylation deficits. The use of these inhibitors as a therapeutic option was efficient in several animal models of neurological disorders. The elaboration of new cell-permeant HAT activators opens a new era of research on acetylation regulation. Although pathological animal models have not been tested yet, HAT activator molecules have already proven to be beneficial in ameliorating brain functions associated with learning and memory, and adult neurogenesis in wild-type animals. Thus, HAT activator molecules contribute to an exciting area of research.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-013-0204-7) contains supplementary material, which is available to authorized users.
doi:10.1007/s13311-013-0204-7
PMCID: PMC3805875  PMID: 24006237
HAT activator molecule; Lysine acetylation; CREB-binding protein; Learning and memory; Adult neurogenesis; Neurodegenerative diseases
11.  A diagnostic scale for Alzheimer’s disease based on cerebrospinal fluid biomarker profiles 
Introduction
The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer’s disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer’s disease (AD) pathologic process.
Methods
For that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-β 42, tau, and p-tau(181) were tested to generate categories of patients with very low (<10%), low (<25%), high (>75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included.
Results
A prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale’s overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The model was also validated in an independent multicenter dataset of 408 patients (213 AD and 195 non-AD).
Conclusions
In conclusion, we defined a new scale that could be used to facilitate the interpretation and routine use of multivariate CSF data, as well as helping the stratification of patients in clinical research trials.
doi:10.1186/alzrt267
PMCID: PMC4255520  PMID: 25478015
12.  Chronic Bickerstaff’s encephalitis with cognitive impairment, a reality? 
BMC Neurology  2014;14:99.
Background
Bickerstaff’s encephalitis (BE) is an acute post-infectious demyelinating disease with albuminocytological dissociation. A chronic form has rarely been described previously.
Case presentation
A 44-year-old man was hospitalized for drowsiness, cognitive complaint limb weakness, ataxia and sensory disturbance after diarrhea. Neuropsychological evaluation showed slowing, memory and executive function impairment, while analysis of the CSF showed albuminocytological dissociation. Immunologic tests showed positive anti-ganglioside antibodies (anti-GM1 IgM, anti-GD1a IgG and anti-GD1b IgM). Brain MRI was normal but SPECT showed bilateral temporal and frontal hypoperfusion. Outcome under immunoglobulin treatment (IVIG) was favorable with an initial improvement but was marked by worsening after a few weeks. Consequently, the patient was treated with IVIG every 2 months due to the recurrence of symptoms after 6 weeks.
Conclusion
This case raises the question of the existence of a chronic form of BE with cognitive impairment, in the same way as chronic inflammatory demyelinating polyneuropathy is considered to be a chronic form of Guillain–Barré syndrome.
doi:10.1186/1471-2377-14-99
PMCID: PMC4040113  PMID: 24885623
Bickerstaff’s encephalitis; Anti-ganglioside antibodies; Chronic encephalitis; Campylobacter jejuni; Molecular mimicry; Cognitive dysfunction; Dementia; Mild cognitive impairment
13.  Guest-Adaptable and Water-Stable Peptide-Based Porous Materials by Imidazolate Side Chain Control** 
The peptide-based porous 3D framework, ZnCar, has been synthesized from Zn2+ and the natural dipeptide carnosine (β-alanyl-L-histidine). Unlike previous extended peptide networks, the imidazole side chain of the histidine residue is deprotonated to afford Zn–imidazolate chains, with bonding similar to the zeolitic imidazolate framework (ZIF) family of porous materials. ZnCar exhibits permanent microporosity with a surface area of 448 m2 g−1, and its pores are 1D channels with 5 Å openings and a characteristic chiral shape. This compound is chemically stable in organic solvents and water. Single-crystal X-ray diffraction (XRD) showed that the ZnCar framework adapts to MeOH and H2O guests because of the torsional flexibility of the main His-β-Ala chain, while retaining the rigidity conferred by the Zn–imidazolate chains. The conformation adopted by carnosine is driven by the H bonds formed both to other dipeptides and to the guests, permitting the observed structural transformations.
doi:10.1002/anie.201307074
PMCID: PMC3995008  PMID: 24302659
imidazolates; metal–organic frameworks; microporous materials; peptides; structural adaptability
14.  Shedding Light on Structure–Property Relationships for Conjugated Microporous Polymers: The Importance of Rings and Strain 
Macromolecules  2013;46(19):7696-7704.
The photophysical properties of insoluble porous pyrene networks, which are central to their function, differ strongly from those of analogous soluble linear and branched polymers and dendrimers. This can be rationalized by the presence of strained closed rings in the networks. A combined experimental and computational approach was used to obtain atomic scale insight into the structure of amorphous conjugated microporous polymers. The optical absorption and fluorescence spectra of a series of pyrene-based materials were compared with theoretical time-dependent density functional theory predictions for model clusters. Comparison of computation and experiment sheds light on the probable structural chromophores in the various materials.
doi:10.1021/ma401311s
PMCID: PMC3805316  PMID: 24159243
15.  Evaluation of Clinical Interest of Anti-Aquaporin-4 Autoantibody Followup in Neuromyelitis Optica 
Neuromyelitis optica (NMO) is an autoimmune disease in which a specific biomarker named NMO-IgG and directed against aquaporin-4 (AQP4) has been found. A correlation between disease activity and anti-AQP4 antibody (Ab) serum concentration or complement-mediated cytotoxicity has been reported, but the usefulness of longitudinal evaluation of these parameters remains to be evaluated in actual clinical practice. Thirty serum samples from 10 NMO patients positive for NMO-IgG were collected from 2006 to 2011. Anti-AQP4 Ab serum concentration and complement-mediated cytotoxicity were measured by flow cytometry using two quantitative cell-based assays (CBA) and compared with clinical parameters. We found a strong correlation between serum anti-AQP4 Ab concentration and complement-mediated cytotoxicity (P < 0.0001). Nevertheless, neither relapse nor worsening of impairment level was closely associated with a significant increase in serum Ab concentration or cytotoxicity. These results suggest that complement-mediated serum cytotoxicity assessment does not provide extra insight compared to anti-AQP4 Ab serum concentration. Furthermore, none of these parameters appears closely related to disease activity and/or severity. Therefore, in clinical practice, serum anti-AQP4 reactivity seems not helpful as a predictive biomarker in the followup of NMO patients as a means of predicting the onset of a relapse and adapting the treatment accordingly.
doi:10.1155/2013/146219
PMCID: PMC3655457  PMID: 23710199
16.  Induced Brain Plasticity after a Facilitation Programme for Autobiographical Memory in Multiple Sclerosis: A Preliminary Study 
This preliminary study tackles the assessment and treatment of autobiographical memory (AbM) in relapsing-remitting multiple sclerosis (RR-MS) patients. Our aim was to investigate cerebral activation changes, following clinical improvement of AbM due to a cognitive training based on mental visual imagery (MVI). We assessed AbM using the Autobiographical Interview (AI) in eight patients and 15 controls. The latter subjects established normative data. The eight patients showed selective defective performance on the AI. Four patients were trained cognitively and underwent pre- and post-AI and fMRI. The remaining four patients took a second AI, at the same interval, but with no intervention in between. Results showed a significant improvement of AbM performance after the facilitation programme that could not be explained by learning effects since the AI scores remained stable between the two assessments in the second group of patients. As expected, AbM improvement was accompanied by an increased cerebral activity in posterior cerebral regions in post-facilitation fMRI examination. We interpret this activation changes in terms of reflecting the emphasis made on the role of MVI in memory retrieval through the facilitation programme. These preliminary significant clinical and neuroimaging changes suggest the beneficial effects of this technique to alleviate AbM retrieval deficit in MS patients.
doi:10.1155/2012/820240
PMCID: PMC3483777  PMID: 23125932
17.  MRI-Based Volumetry Correlates of Autobiographical Memory in Alzheimer's Disease 
PLoS ONE  2012;7(10):e46200.
The aim of the present volumetric study was to explore the neuro-anatomical correlates of autobiographical memory loss in Alzheimer's patients and healthy elderly, in terms of the delay of retention, with a particular interest in the medial temporal lobe structures. Fifteen patients in early stages of the disease and 11 matched control subjects were included in the study. To assess autobiographical memory and the effect of the retention delay, a modified version of the Crovitz test was used according to five periods of life. Autobiographical memory deficits were correlated to local atrophy via structural MRI using Voxel Based Morphometry. We used a ‘lateralized index’ to compare the relative contribution of hippocampal sub-regions (anterior vs posterior, left vs right) according to the different periods of life. Our results confirm the involvement of the hippocampus proper in autobiographical memory retrieval for both recent and very remote encoding periods, with larger aspect for the very remote period on the left side. Contrary to the prominent left-sided involvement for the young adulthood period, the implication of the right hippocampus prevails for the more recent periods and decreases with the remotness of the memories, which might be associated with the visuo-spatial processing of the memories. Finally, we suggest the existence of a rostrocaudal gradient depending on the retention duration, with left anterior aspects specifically related to retrieval deficits of remote memories from the young adulthood period, whereas posterior aspects would result of simultaneous encoding and/or consolidation and retrieval deficit of more recent memories.
doi:10.1371/journal.pone.0046200
PMCID: PMC3468599  PMID: 23071546
18.  Inflammatory-like presentation of CADASIL: a diagnostic challenge 
BMC Neurology  2012;12:78.
Background
CADASIL is an autosomal dominant genetic leukoencephalopathy linked to mutations in the Notch3 gene. In rare cases, widespread brain lesions on T2 MRI mimicking multiple sclerosis are observed. From a national registry of 268 patients with adult-onset leukodystrophy, we identified two patients with an atypical presentation of CADASIL without co-occurrence of another systemic disease.
Case presentations
Patient 1 experienced progressive gait disability and patient 2 relapsing optic neuritis and sensory-motor deficit in the leg. Both patients responded to corticotherapy and patient 2 was also responsive to glatiramer acetate. No oligoclonal bands were found in the CSF, and MRI showed myelitis and lesions with gadolinium enhancement in brain (patient 1) or incomplete CADASIL phenotype (patient 2).
Conclusions
In rare cases, an inflammatory-like process can occur in CADASIL. In these patients, immunomodulatory treatments, including corticosteroids, could be effective.
doi:10.1186/1471-2377-12-78
PMCID: PMC3488471  PMID: 22905984
CADASIL; Multiple sclerosis; Leukoencephalopathy; Notch3; Cerebral vasculitis

Results 1-18 (18)