Development, Spanish Normative Data, and Validation of a Social Cognition Battery in Prodromal Alzheimer's Disease and Multiple Sclerosis.

OBJECTIVES: The assessment of social cognition changes may be challenging, especially in the earliest stages of some neurodegenerative diseases. Our objective was to validate a social cognition battery from a multidomain perspective. In this regard, we aimed to adapt several tests, collect normative data, and validate them in prodromal Alzheimer's disease (AD) and multiple sclerosis (MS). METHODS: A total of 92 healthy controls, 25 prodromal AD, and 39 MS patients were enrolled. Age-, gender-, and education-matched control groups were created for comparisons. Social cognition battery was composed of an emotion-labeling task developed from FACES database, the Story-based Empathy test (SET), the Faux Pas test, and the Interpersonal Reactivity Index. Patients were also evaluated with a comprehensive cognitive battery to evaluate the other cognitive domains. Automatic linear modeling was used to predict each social cognition test's performance using the neuropsychological tests examining other cognitive domains. RESULTS: The reliability of the battery was moderate-high. Significant intergroup differences were found with medium-large effect sizes. Moderate correlations were found between social cognition battery and neuropsychological tests. The emotion labeling task and SET showed moderate correlations with age and education, and age, respectively. Regression-based norms were created considering the relevant demographic variables. Linear regression models including other neuropsychological tests explained between 7.7% and 68.8% of the variance of the social cognition tests performance. CONCLUSIONS: Our study provides a battery for the assessment of social cognition in prodromal AD and MS with Spanish normative data to improve the evaluation in clinical and research settings.

Reading prosody in the non-fluent and logopenic variants of primary progressive aphasia.

BACKGROUND: Primary progressive aphasia (PPA) is a clinical syndrome including a group of neurodegenerative disorders that present with language impairment. We hypothesised that impairment in reading prosody may be present in a subgroup of patients with PPA, and particularly non-fluent PPA (nfvPPA), because of the impairment of key brain regions involved in the pathophysiology of speech dysprosody and reading observed in these patients. METHODS: Ninety-five participants were evaluated using a narrative text comprising several declarative, exclamatory, and interrogative sentences, as well as a comprehensive language protocol. Patients were also examined with 18F-fluorodeoxyglucose positron emission tomography imaging. RESULTS: Impairment was more frequent and more severe in patients with nfvPPA, especially in the subgroup of patients with Apraxia of Speech (AOS). Patients with nfvPPA, mainly those with AOS, showed lower values in several pitch variables. Statistically significant differences were also observed in sentence duration, reading times, and types of error. A regression model including mean length of utterances, time after full stops, number of pauses, and number of pitch variables below the mean, correctly classified 70-71.3% of patients. When combined with sentence repetition task, the percentage of patients correctly classified was 96.2% and 92.4%, respectively, for each classification. The left frontal lobe was the region most strongly correlated with reading prosody parameters. Specific tasks displayed additional correlations with the left parietal and occipital lobes; right frontal lobe, thalamus, and caudate; and right cerebellum. CONCLUSION: Reading prosody is relevant in PPA diagnosis and classification. Because reading prosody may be quantified, it is amenable to use in diagnosis and follow-up. We found neuroimaging correlation with metabolism in the left frontal lobe, as well as in other regions including the right frontal lobe, basal ganglia, and cerebellum, which suggests that these may be the main brain regions involved in prosodic control in patients with PPA.

Memory Impairment in Relapsing-Remitting Multiple Sclerosis Using a Challenging Semantic Interference Task.

Objective: Episodic memory is frequently impaired in Multiple Sclerosis (MS), but the cognitive characteristics and neuropsychological processes involved remain controversial. Our aim was to study episodic memory dysfunction in MS, using the LASSI-L, a novel memory-based cognitive stress test that uses a new paradigm that capitalizes on semantic interference. Methods: Cross-sectional study in which 93 patients with MS (relapsing-remitting) and 124 healthy controls were included. The LASSI-L test was administered to all participants, as well as a comprehensive neuropsychological battery including a selective reminding test. MS patients were divided into two groups, with cognitive impairment (CI-MS) and cognitively preserved (CP-MS). Results: Reliability of the LASSI-L test was high (Cronbach's alpha 0.892) and there were less ceiling effects. MS patients scored lower than controls on all LASSI-L subtests, except for maximum storage of the initial target items (CRA2). Effect sizes were moderate-large. A delay in learning, difficulties in retroactive semantic interference, failure to recover from proactive semantic interference, and delayed recall were the most frequent findings in MS patients. Scores associated with maximum storage capacity, and retroactive semantic interference were the most strongly associated with cognitive impairment and employment status. Conclusion: We found that deficits in maximum learning, difficulties in recovery from the effects of proactive semantic interference and retroactive semantic interference are three important breakdowns in episodic memory deficits among patients with MS. The LASSI-L showed good psychometric and diagnostic properties. Overall, our study supports the utility of the LASSI-L, as a new cognitive test, useful for neuropsychological assessment in MS in clinical and research settings.

Amyloid PET findings in multiple sclerosis are associated with cognitive decline at 18 months.

OBJECTIVE: To study the clinical, cognitive, and radiological progression of a cohort of patients with MS, taking into account the amyloid PET with 18F-florbetaben analyses. METHODS: Twenty-nine patients with MS were assessed with longitudinal structural MRI and a clinical and comprehensive neuropsychological protocol, with a mean interval between assessments of 18 ± 3.31 months. 18F-florbetaben PET was performed at baseline. Uptake was analysed in demyelinating plaques (DWM) and normal-appearing white matter (NAWM). Results were correlated with clinical, cognitive and MRI data. RESULTS: Patients with cognitive decline over the follow-up period showed a lower standardised uptake value ratio in NAWM and lower thalamic volume and a higher lesion load in the baseline MRI. Myelin status was correlated with EDSS and cognitive tests mainly evaluating visuospatial function and working memory. Lower uptake in NAWM at baseline was also associated with a growth in white matter lesion volume over time. CONCLUSIONS: Lower white matter uptake in amyloid PET is associated with cognitive decline and an increase in white matter lesion volume during the follow-up. Our study suggests that 18F-florbetaben may be a useful biomarker in assessing myelin status in MS, understanding MS pathophysiology, and predicting cognitive outcomes.

Plasma Neurofilament Light Chain in Primary Progressive Aphasia and Related Disorders: Clinical Significance and Metabolic Correlates.

BACKGROUND: Primary progressive aphasia (PPA) is a heterogeneous syndrome that is difficult to diagnose at early stages. Plasma neurofilament light chain (NFL) has been proposed as a potential biomarker for PPA. OBJECTIVE: To examine the diagnostic properties of plasma NFL in PPA and to evaluate its association with clinical stages of the disease and brain metabolism. METHODS: Our study included 80 participants (13 with non-fluent, 12 with semantic, and 16 with logopenic variant PPA; 13 with amnestic Alzheimer's disease [AD]; 13 with behavioral variant frontotemporal dementia; and 13 healthy controls). Plasma NFL concentration was measured using a high-sensitivity enzyme-linked immunosorbent assay (ELISA) kit. PET imaging was performed in a subgroup of patients. RESULTS: NFL discriminated patients from controls with an area under the curve of 0.914 (95% CI, 0.843-0.984; p < 0.001) (cut-off: 76.46 pg/mL; 94% sensitivity, 76.9% specificity). There were no significant differences between clinical syndromes (PPA subtypes), the main clinical forms of dementia (frontotemporal dementia and AD), or the expected pathological groups (frontotemporal lobar degeneration-tau [FTLD-tau], FTLD-TDP43, and AD). NFL levels showed weak to moderate correlations with age and functional scale score. We found no significant correlation with the extent of hypometabolism observed on FDG-PET images. CONCLUSION: Plasma NFL is a non-specific marker of neurodegeneration, and may be helpful in the diagnosis of PPA. However, NFL does not permit differential diagnosis between PPA subtypes and is not correlated with the extent of neurodegeneration.

Exosomal HSP70 for Monitoring of Frontotemporal Dementia and Alzheimer's Disease: Clinical and FDG-PET Correlation.

We aimed to study the expression of circulating heat-shock protein HSP70 and exosomes in plasma of a cohort of patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) at different stages. We performed correlations with clinical scales and FDG-PET. HSP70 levels were higher within exosomes than free in plasma. Moderate correlations were found between exosomal HSP70 and CDR, FTLD-CDR, and extension of hypometabolism. Our results suggest modifications in the level of exosomal HSP70 during the course of neurodegeneration, regardless of AD or FTD, and therefore HSP70 could have a potential role in the follow-up of these disorders.

Machine learning in the clinical and language characterisation of primary progressive aphasia variants.

INTRODUCTION: Primary progressive aphasia (PPA) is a clinical syndrome of neurodegenerative origin with 3 main variants: non-fluent, semantic, and logopenic. However, there is some controversy about the existence of additional subtypes. Our aim was to study the language and cognitive features associated with a new proposed classification for PPA. MATERIAL AND METHODS: Sixty-eight patients with PPA in early stages of the disease and 20 healthy controls were assessed with a comprehensive language and cognitive protocol. They were also evaluated with 18F-FDG positron emision tomography (PET). Patients were classified according to FDG PET regional metabolism, using our previously developed algorithm based on a hierarchical agglomerative cluster analysis with Ward's linkage method. Five variants were found, with both the non-fluent and logopenic variants being split into 2 subtypes. Machine learning techniques were used to predict each variant according to language assessment results. RESULTS: Non-fluent type 1 was associated with poorer performance in repetition of sentences and reading of irregular words than non-fluent type 2. Conversely, the second group showed a higher degree of apraxia of speech. Patients with logopenic variant type 1 performed more poorly on action naming than patients with logopenic type 2. Language assessments were predictive of PET-based subtypes in 86%-89% of cases using clustering analysis and principal components analysis. CONCLUSIONS: Our study supports the existence of 5 variants of PPA. These variants show some differences in language and FDG PET imaging characteristics. Machine learning algorithms using language test data were able to predict each of the 5 PPA variants with a relatively high degree of accuracy, and enable the possibility of automated, machine-aided diagnosis of PPA variants.

What is the meaning of PASAT rejection in multiple sclerosis?

BACKGROUND: Paced Auditory Serial Addition Test (PASAT) is one of the most used neuropsychological tests in multiple sclerosis (MS), specially for screening. However, the applicability of the test is limited because of the rejection of the test completion in a proportion of patients. We aimed to investigate the clinical, neuropsychological, and MRI findings associated to PASAT rejection. METHODS: Cross-sectional and observational study. A total of 343 patients with MS underwent neuropsychological testing and structural MRI. RESULTS: One hundred and twenty-one (35.3%) of patients declined the administration of the test. Among those patients that declined the administration, rejection occurred before the onset of test in 35.5%, during or after the practice in 43%, and during the test administration in 21.5%. Rejection of the test was associated to a worse performance in all cognitive tests administered, but not to depression or baseline fatigue scales. In regression analysis, education, cognitive impairment, EDSS, and white matter lesion load were independently associated to rejection of the test. CONCLUSIONS: Paced Auditory Serial Addition Test rejection is associated with a higher probability of cognitive impairment in MS. This suggests that patients that reject the administration of PASAT should be further examined with a neuropsychological battery to evaluate the possibility of cognitive dysfunction.

Inhibition impairment in frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer's disease: clinical assessment and metabolic correlates.

The ability to reject an automatic tendency, i.e. inhibition, has been linked to the prefrontal cortex, but its neural underpinnings are still controversial. Neurodegenerative diseases represent an interesting model to explore this issue, given its frequent impairment in these disorders. We investigated the inhibitory impairment and its neural basis using four different tests, which evaluate the presence of inhibitory dysfunction (Stroop test, Hayling test, and two graphical perseveration tests), and assessed their correlation with brain metabolism using 18F-fluorodeoxyglucose positron emission tomography in a group of 76 participants with behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and healthy controls (HC). Inhibition impairment was more frequent in bvFTD and AD, than ALS and HC. AD and bvFTD only differed in the strategy used in Hayling test, and the frequency of impairment in graphical perseveration tests. Correlation between inhibition tests was moderate. The Stroop test correlated with several regions of the frontal and parietal lobes, mainly on the left side. Hayling test correlated with almost all regions of the frontal lobe and, especially, with the orbitofrontal cortex. Some differences in the impaired regions in each disease were found. Inhibition ability was mainly impaired in bvFTD and AD, and it correlated with the bilateral frontal lobe metabolism. There were certain particularities according to the specific task and patients evaluated. These dissimilarities may support the concept of inhibition as a multidimensional construct, with the involvement of common and divergent neural mechanisms.

Structural MRI correlates of PASAT performance in multiple sclerosis.

BACKGROUND: The Paced Auditory Serial Addition Test (PASAT) is a useful cognitive test in patients with multiple sclerosis (MS), assessing sustained attention and information processing speed. However, the neural underpinnings of performance in the test are controversial. We aimed to study the neural basis of PASAT performance by using structural magnetic resonance imaging (MRI) in a series of 242 patients with MS. METHODS: PASAT (3-s) was administered together with a comprehensive neuropsychological battery. Global brain volumes and total T2-weighted lesion volumes were estimated. Voxel-based morphometry and lesion symptom mapping analyses were performed. RESULTS: Mean PASAT score was 42.98 ± 10.44; results indicated impairment in 75 cases (31.0%). PASAT score was correlated with several clusters involving the following regions: bilateral precuneus and posterior cingulate, bilateral caudate and putamen, and bilateral cerebellum. Voxel-based lesion symptom mapping showed no significant clusters. Region of interest-based analysis restricted to white matter regions revealed a correlation with the left cingulum, corpus callosum, bilateral corticospinal tracts, and right arcuate fasciculus. Correlations between PASAT scores and global volumes were weak. CONCLUSION: PASAT score was associated with regional volumes of the posterior cingulate/precuneus and several subcortical structures, specifically the caudate, putamen, and cerebellum. This emphasises the role of both cortical and subcortical structures in cognitive functioning and information processing speed in patients with MS.

Identification of Cortical and Subcortical Correlates of Cognitive Performance in Multiple Sclerosis Using Voxel-Based Morphometry.

Objective: Cognitive impairment is an important feature in multiple sclerosis (MS) and has been associated to several Magnetic Resonance Imaging (MRI) markers, but especially brain atrophy. However, the relationship between specific neuropsychological tests examining several cognitive functions and brain volumes has been little explored. Furthermore, because MS frequently damage subcortical regions, it may be an interesting model to examine the role of subcortical areas in cognitive functioning. Our aim was to identify correlations between specific brain regions and performance in neuropsychological tests evaluating different cognitive functions in a large series of patients with MS. Methods: A total of 375 patients were evaluated with a comprehensive neuropsychological battery and with MRI. Voxel-based morphometry was conducted to analyse the correlation between cognitive performance and gray matter damage, using Statistical Parametric Mapping with the toolboxes VBM8 and Lesion Segmentation Tool. Results: The following correlations were found: Corsi block-tapping test with right insula; Trail Making Test with caudate nucleus, thalamus, and several cortical regions including the posterior cingulate and inferior frontal gyrus; Symbol Digit Modalities Test with caudate nucleus, thalamus, posterior cingulate, several frontal regions, insula, and cerebellum; Stroop Color and Word Test with caudate nucleus and putamen; Free and Cued Selective Reminding Test and Rey-Osterrieth Complex Figure with thalamus, precuneus, and parahippocampal gyrus; Boston Naming Test with thalamus, caudate nucleus, and hippocampus; semantic verbal fluency with thalamus and phonological verbal fluency with caudate nucleus; and Tower of London test with frontal lobe, caudate nucleus, and posterior cingulate. Conclusion: Our study provides valuable data on the cortical and subcortical basis of cognitive function in MS. Neuropsychological tests mainly assessing attention and executive function showed a stronger association with caudate volume, while tests primarily evaluating memory were more strongly correlated with the thalamus. Other relevant regions were the posterior cingulate/precuneus, which were associated with attentional tasks, and several frontal regions, which were found to be correlated with planning and higher order executive functioning. Furthermore, our study supports the brain vertical organization of cognitive functioning, with the participation of the cortex, thalamus, basal ganglia, and cerebellum.

Clustering Analysis of FDG-PET Imaging in Primary Progressive Aphasia.

Background: Primary progressive aphasia (PPA) is a clinical syndrome characterized by the neurodegeneration of language brain systems. Three main clinical forms (non-fluent, semantic, and logopenic PPA) have been recognized, but applicability of the classification and the capacity to predict the underlying pathology is controversial. We aimed to study FDG-PET imaging data in a large consecutive case series of patients with PPA to cluster them into different subtypes according to regional brain metabolism. Methods: 122 FDG-PET imaging studies belonging to 91 PPA patients and 28 healthy controls were included. We developed a hierarchical agglomerative cluster analysis with Ward's linkage method, an unsupervised clustering algorithm. We conducted voxel-based brain mapping analysis to evaluate the patterns of hypometabolism of each identified cluster. Results: Cluster analysis confirmed the three current PPA variants, but the optimal number of clusters according to Davies-Bouldin index was 6 subtypes of PPA. This classification resulted from splitting non-fluent variant into three subtypes, while logopenic PPA was split into two subtypes. Voxel-brain mapping analysis displayed different patterns of hypometabolism for each PPA group. New subtypes also showed a different clinical course and were predictive of amyloid imaging results. Conclusion: Our study found that there are more than the three already recognized subtypes of PPA. These new subtypes were more predictive of clinical course and showed different neuroimaging patterns. Our results support the usefulness of FDG-PET in evaluating PPA, and the applicability of computational methods in the analysis of brain metabolism for improving the classification of neurodegenerative disorders.

Familial multiple sclerosis and association with other autoimmune diseases.

Objectives: Autoimmune diseases (AID) follow a complex, probably polygenic, pattern of inheritance and often cluster in families of patients with multiple sclerosis (MS). Our objective was to analyze family patterns and characteristics in families including more than one patient with MS. Materials and Methods: We analyzed personal and family history of neurological, systemic, and autoimmune diseases in 84 MS patients from 40 different families. Families were classified in two groups: families with cases of MS in at least two different generations (15 families) and families in which cases of MS belonged to only one generation (25 families). Results: The two previously established groups presented different clinical patterns and frequency of association with another AID. In one group, the second generation displayed a higher annual relapse rate than the first generation, higher frequency of progressive forms of MS, and more patients with another AID in addition to MS. Relapsing-remitting forms of MS (RRMS) were more frequent in the other group. Conclusions: Families that include more than one MS patient may show two distinct patterns. This finding seems important for the compression and analysis of genetic information on MS.

Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease.

OBJECTIVES: Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18 F fluorodeoxyglucose (FDG-PET). METHODS: Forty-two bvFTD, 42 AD, and 30 healthy volunteers without cognitive or behavioral complaints were included. Apathy was defined using Robert's 2009 diagnostic criteria, and specific apathy characteristics were assessed with the Lille Apathy Rating Scale. All participants underwent FDG-PET brain scan to provide data for voxel-based morphometric analysis. RESULTS: Multivariate analysis showed that subjects affected by bvFTD displayed greater impairment of emotional apathy and self-awareness in comparison with AD sample. Additionally, FDG-PET imaging analyses revealed that apathy was associated with different neuroanatomical substrates in each dementia group: left lateral prefrontal, medial frontal/anterior cingulate, lateral orbitofrontal and anterior insular cortices in bvFTD, and right anterior cingulate in AD. CONCLUSIONS: These results support that apathy is a complex syndrome, with different clinical expressions across different pathological conditions. Those differences in qualitative aspects of apathy seem to be associated with differences in the damage sites, as shown by our FDG-PET imaging analysis. Our findings provide a better knowledge about pathophysiology of apathy in dementia, which could have practical implications for therapeutic management. Copyright © 2017 John Wiley & Sons, Ltd.

Comparison between FCSRT and LASSI-L to Detect Early Stage Alzheimer's Disease.

BACKGROUND: The Free and Cued Selective Reminding Test (FCSRT) is the most accurate test for the diagnosis of prodromal Alzheimer's disease (AD). Recently, a novel cognitive test, the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), has been developed in order to provide an early diagnosis. OBJECTIVE: To compare the diagnostic accuracy of the FCSRT and the LASSI-L for the diagnosis of AD in its preclinical and prodromal stages using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a reference. METHODS: Fifty patients consulting for subjective memory complaints without functional impairment and at risk for AD were enrolled and evaluated using FCSRT, LASSI-L, and FDG-PET. Participants were evaluated using a comprehensive neurological and neuropsychological protocol and were assessed with the FCSRT and LASSI-L. FDG-PET was acquired concomitantly and used for classification of patients as AD or non-AD according to brain metabolism using both visual and semi-quantitative methods. RESULTS: LASSI-L scores allowed a better classification of patients as AD/non-AD in comparison to FCSRT. Logistic regression analysis showed delayed recall and failure to recovery from proactive semantic interference from LASSI-L as independent statistically significant predictors, obtaining an area under the curve of 0.894. This area under the curve provided a better discrimination than the best FCSRT score (total delayed recall, area under the curve 0.708, p = 0.029). CONCLUSIONS: The LASSI-L, a cognitive stress test, was superior to FCSRT in the prediction of AD features on FDG-PET. This emphasizes the possibility to advance toward an earlier diagnosis of AD from a clinical perspective.

Conversion between Addenbrooke's Cognitive Examination III and Mini-Mental State Examination.

ABSTRACTBackground:We aim to provide a conversion between Addenbrooke's Cognitive Examination III (ACE-III) and Mini-Mental State Examination (MMSE) scores, to predict the MMSE result based on ACE-III, thus avoiding the need for both tests, and improving their comparability. METHODS: Equipercentile equating method was used to elaborate a conversion table using a group of 400 participants comprising healthy controls and Alzheimer's disease (AD) patients. Then, reliability was assessed in a group of 100 healthy controls and patients with AD, 52 with primary progressive aphasia and 22 with behavioral variant frontotemporal dementia. RESULTS: The conversion table between ACE-III and MMSE denoted a high reliability, with intra-class correlation coefficients of 0.940, 0.922, and 0.902 in the groups of healthy controls and AD, behavioral variant frontotemporal dementia, and primary progressive aphasia, respectively. CONCLUSION: Our conversion table between ACE-III and MMSE suggests that MMSE may be estimated based on the ACE-III score, which could be useful for clinical and research purposes.

Functional Components of Cognitive Impairment in Multiple Sclerosis: A Cross-Sectional Investigation.

BACKGROUND: Cognitive impairment is frequent and disabling in multiple sclerosis (MS). Changes in information processing speed constitute the most important cognitive deficit in MS. However, given the clinical and topographical variability of the disease, cognitive impairment may vary greatly and appear in other forms in addition to slower information processing speed. Our aim was to determine the frequency of cognitive impairment, the principal cognitive domains, and components involved in MS and to identify factors associated with presence of cognitive impairment in these patients in a large series of patients. METHODS: Cross-sectional study of 311 patients with MS [236 with relapsing-remitting MS (RRMS), 52 with secondary progressive MS (SPMS), and 23 with primary progressive MS (PPMS)]. Patients' cognitive function was assessed with a comprehensive neuropsychological assessment protocol. Patients displaying deficits in 2 or more cognitive domains were considered to have cognitive impairment associated with MS. We conducted a principal component analysis to detect different cognitive patterns by identifying clusters of tests highly correlated to one another. RESULTS: Cognitive impairment was detected in 41.5% of the sample, and it was more frequent in patients with SPMS and PPMS (P = 0.002). Expanded Disability Status Scale scores and education were independent predictors of cognitive impairment. Principal component analysis identified seven clusters: attention and basic executive function (including information processing speed), planning and high-level executive function, verbal memory and language, executive and visuospatial performance time, fatigue-depression, visuospatial function, and basic attention and verbal/visual working memory. Mean scoring of components 2 (high-order executive functioning) and 3 (verbal memory-language) was higher in patients with RRMS than in those with PPMS (component 2) and SPMS (component 3). CONCLUSION: MS is linked to multiple cognitive profiles and disturbances in different domains. This suggests that cognitive alterations in MS are heterogeneous and affect other domains in addition to information processing speed.

Amyloid PET in pseudotumoral multiple sclerosis.

BACKGROUND: Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter. METHOD: We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer 18F-florbetaben. The patient had developed word-finding difficulties and right hemianopia twelve years ago. In that time, MRI showed a lesion on the left hemisphere with an infiltrating aspect in frontotemporal lobes. Brain biopsy showed demyelinating areas and inflammation. During the following years, two new clinical relapses occurred. RESULTS: 18F-florbetaben PET showed lower uptake in the white matter lesion visualized in the CT and MRI images. Decreased tracer uptake was also observed in a larger area of the left hemisphere beyond the lesions observed on MRI or CT. White matter lesion volume on FLAIR was 44.2mL, and tracer uptake change between damaged white matter and normal appearing white matter was - 40.5%. Standardized uptake value was inferior in the pseudotumoral lesion than in the other white matter lesions. CONCLUSION: We report the findings of amyloid PET in a patient with pseudotumoral multiple sclerosis. This case provides further evidence on the role of amyloid PET in the assessment of white matter and demyelinating diseases.

Reading difficulties in primary progressive aphasia in a regular language-speaking cohort of patients.

Reading impairment is an important feature in Primary Progressive Aphasia (PPA). The Spanish orthography entails completely regular spelling to sound correspondences, so reading disorders may be different to English. In the current study, reading, phonological and semantic abilities of 35 patients with the three variants of PPA, and 13 healthy volunteers were assessed. Brain metabolism was concomitantly obtained from each participant using 18F-fluorodeoxyglucose positron emission tomography imaging. Two main patterns of impairment were identified: difficulties in nonwords reading with preservation of exception words in agrammatic and logopenic aphasia, and the inverse pattern in semantic dementia. Left frontal and left parietotemporal regions were associated to nonwords reading, while the anterior temporal lobe was related to reading of exception words. These results support the usefulness of examining reading abilities in the differential diagnosis of PPA variants, and suggest potential types of words that could be used in Spanish to assess these patients.