A clinical screening tool for objective and subjective cognitive disorders in multiple sclerosis.

BACKGROUND: Cognitive dysfunction is common in multiple sclerosis (MS). Deficits can affect attention, concentration, planning, and memory. They can have severe functional consequences in many domains. Cognitive complaints are frequently associated with other confounding factors (fatigue, anxiety, depression, or treatment side effects). In most cases, cognitive assessment is proposed after a spontaneous complaint, but determining the extent of discomfort perceived by the patient, the influence of coexisting factors, or the optimal timing for a more complete neuropsychological assessment is difficult. OBJECTIVE: The objective of this work was to evaluate the feasibility and relevance of a fast global assessment of both objective and subjective cognitive dysfunction in MS. METHODS: MS patients underwent a brief cognitive assessment including 7 visual analogue scales (VASs) asking about the patient's subjective level of discomfort in various domains, a memory test (Barbizet's lion story), a commonly used test of information processing speed (Symbol Digit Modalities Test [SDMT]) and self-reporting questionnaires for fatigue and mood (Fatigue Severity Scale [FSS] and Hospital Anxiety and Depression Scale [HADS]). Spearman correlation coefficients among scores were estimated. RESULTS: The mean age of the 73 patients included was 48.3 (SD 11.1) years; 78% were females and 52.8% had the remittent-recurrent MS form, 8.3% the primary progressive form, and 38.9% the secondary progressive form. In less than 20min, this brief cognitive assessment was able to identify symptoms and quantify discomfort level. Symptoms of fatigue and anxiety frequently coexisted with cognitive complaints. We found modest correlations between scores on the VAS fatigue and the FSS and between scores on the VAS mood and the HADS. Analytical evaluation revealed that most patients had similar SDMT and recall profiles; however, a small proportion showed a dissociation between these 2 tests, which validated the inclusion of both tests in the assessment. Accounting for coexisting factors (e.g., anxiety and fatigue) and their functional repercussions is essential for prioritizing these problems within the context of multidisciplinary patient treatment. CONCLUSION: Considering the possible multifactorial character of cognitive dysfunction in MS, it is essential to ask patients about their experiences and to take into account cognitive complaints in the follow-up of patients. The assessment tool we propose is simple and easy to use in a clinical setting and provides the information necessary for requesting (or not) a more complete neuropsychological assessment.

Initial memory deficit profiles in patients with a cerebrospinal fluid Alzheimer's disease signature.

BACKGROUND: Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a progressive memory deficit. The proportion of typical medial-temporal amnesia revealing AD remains unknown. OBJECTIVE: The present study explores the episodic memory impairment profiles by the Free and Cued Selective Recall Reminding Test (FCSRT) in patients with initial memory complaint and a cerebrospinal fluid (CSF) biomarker signature of AD. METHODS: Seventy-three patients referred for memory complaint to the Centers for Memory, Resource and Research of Lyon and Montpellier (France) were included consecutively. All patients underwent an extensive neuropsychological examination and had a Mini-Mental State Examination (MMSE) score ≥20 and a positive CSF AD signature. The patients were classified as having mild dementia or prodromal AD. Verbal episodic memory was assessed using the French version of the FCSRT exploring encoding, storage/consolidation, and cued delayed retrieval phases of memorization. Three different memory profiles were identified according to the results of FCSRT. RESULTS: The median age was 72 year-old [interquartiles: 65-76]. The median MMSE score was 23 [interquartiles: 21-25]. 88% of the patients (n = 64) presented with a medial temporal amnesia profile. The dysexecutive amnesia and normal verbal episodic memory profiles represented respectively 5% (n = 4) and 7% (n = 5). There were no significant differences in term of age, gender, and MMSE score between the three profile groups. CONCLUSION: In a population initially presenting with memory complaints and depicting a CSF AD signature, a high proportion of medial temporal amnesia is disclosed as expected, but also a proportion of dysexecutive amnesia and normal FCSRT.

In vivo demonstration of amyloid burden in posterior cortical atrophy: a case series with PET and CSF findings.

Our objective was to evaluate amyloid deposition in posterior cortical atrophy (PCA), using both cerebrospinal fluid (CSF) biomarker analysis and amyloid imaging. Five PCA patients, selected based on their neuropsychological profile and atrophic changes in posterior regions on MRI, underwent CSF analysis. CSF amyloid-beta 1-42, total tau, and phosphorylated tau at threonine 181 levels were determined. They also had positron emission tomography (PET) with Pittsburgh Compound B ([(11)C]PIB). [(11)C]PIB ratio images were assessed with visual, regional and voxel-based analyses and compared to eight typical Alzheimer's disease (AD) patients and eight controls. The biological profile in the five PCA patients, resulting from CSF and [(11)C]PIB images analysis, was consistent with AD. Individual comparisons of PCA patients' [(11)C]PIB images with the AD group with Statistical Parametric Mapping (SPM) revealed a distinctive posterior uptake in four out of the five patients showing increased amyloid deposition in occipital, temporal, and/or parietal regions. ROI group analysis showed a tendency for higher amyloid deposition in occipital and temporal regions. However, this pattern was not found with SPM group analysis when the global level of [(11)C]PIB uptake was used as a covariate. Our results indicate that amyloid burden can be demonstrated in vivo in PCA suggesting a diagnosis of AD. PCA patients may present a higher global amyloid load than AD that was not related to age at onset, disease severity, disease duration, or educational level in our study. Combined CSF and PET biomarkers seem helpful for in vivo diagnosis of this focal syndrome with underlying AD pathology.

Impaired social cognition in mild Alzheimer disease.

Abnormal decoding of social information has been associated with the conversion from prodromal Alzheimer's disease (AD) to dementia. Since the distributed neural networks involved in face processing are differentially affected in prodromal and dementia states of AD and in Fronto-Temporal Dementia (FTD), we hypothesized a differential impairment in face processing in these populations. Facial expression, gender and gaze direction decoding abilities were examined in patients with probable amnesic Mild Cognitive Impairment (aMCI, N=10) fulfilling criteria for prodromal AD, in patients with mild and moderate AD (N=10) as well as in FTD patients (N=10) and in a group of age- and sex-matched healthy comparison subjects (N=10). Gender recognition was preserved in all groups. Compared to controls, patients with mild or moderate AD were impaired in expression recognition and FTD patients were impaired in expression and gaze direction determination, whereas MCI patients were not impaired at all.

Mismatch negativity (MMN) in multiple sclerosis: an event-related potentials study in 46 patients.

OBJECTIVE: To assess pre-attentive detection mechanisms indexed by MMN component of auditory Event-Related Potentials (ERPs) in Multiple Sclerosis (MS) patients. METHODS: 46 MS patients (mean age 43.7 years, mean disease duration 10.1 years, mean EDSS 4.6) and 46 matched controls were assessed with ERPs elicited by a passive oddball paradigm using duration deviants. Auditory P50, N1, P2 components were recorded. MMN and P3a components were calculated as the difference potential between deviants and standard stimuli. Eighteen of these 46 patients underwent also global psychometrical assessment and were sorted in cognitively normal and impaired patients. ERPs of these two groups of patients were compared. RESULTS: MS patients showed reduced MMN and P3a areas as compared to controls, besides exogenous N1-P2 complex amplitude reduction. Among the 18 patients investigated with neuropsychological testings, six were cognitively impaired and 12 cognitively unimpaired. Patients with a global cognitive impairment had reduced MMN as compared to cognitively unimpaired patients. CONCLUSIONS: Auditory MMN and P3a components of auditory ERPs are altered in MS patients. MMN alterations are more pronounced in cognitively impaired patients. SIGNIFICANCE: MMN and P3a areas reduction suggests that MS patients are prone to pre-attentive auditory information processing deficits, besides previously described controlled information processing difficulties. Moreover, MMN alterations may represent an objective index of cognitive disturbances in MS patients.