Clusters of Dementia Literacy: Implications from a Survey of Older Adults.

Clinicians and scientists suggest that up to 40% of dementia cases are potentially preventable. Data on awareness of dementia risk and protective factor among older adults can inform and facilitate designing educational interventions to prevent dementia. We aimed to quantify awareness of dementia risk and protective factors using a telephone survey. The modified Lifestyle for Brain Health scale was used to assess dementia risk and prevention knowledge. A representative sample of 1,005 older adults, mean age 64.02 (standard deviation + 1.4; range: 50-74 years) completed the survey (77% response rate). Under representation of non-European ethnicities was noted. Participants Respondents were all New Zealanders, more women (n=518, 51.5%), mostly European (n=921, 91.6%) and well educated (n=347, 34.5%, university or post-graduate degree). Only 6/14 modifiable risk or protective factors for dementia were adequately identified. Three clusters of dementia literacy were identified: psychosocial, medical and activities. These findings support personalizing dementia prevention efforts via targeted educational packages.

Tooth Loss and Dementia: A Critical Examination.

Dementia is a major contributor to dependence and disability in older people, with aging societies characterized by growing numbers of people living with the condition. Dementia rates are highest in those with low education early in life, midlife hypertension, midlife hearing loss, depression, obesity, loneliness, a sedentary lifestyle, or sustained exposure to smoking or diabetes. Tooth loss is a putative risk factor for dementia which has received increasing research attention, but systematic review findings are mixed. Three main mechanisms have been proposed, involving 1) tooth loss leading to compromised nutrition and then leading to poorer central nervous system (CNS) function; 2) tooth loss resulting in fewer interocclusal contacts and so less somatosensory feedback to the CNS, leading to impaired cognition; and (3) chronic periodontitis resulting in tooth loss, but not before the inflammation has affected the CNS, impairing cognition. None of these is supported by compelling empirical evidence. Here, we use the life course approach to propose a plausible, empirically supported explanation for the associations between missing teeth and poorer cognitive function in older people. Evidence from longstanding cohort studies demonstrates that the putative association arises from cognitive function much earlier in life, in childhood. People with better childhood cognitive function have better oral health and access to routine dental care as they go through life, losing fewer teeth along the life course. They are also much more likely to have better cognitive function in old age. Their less cognitively able childhood counterparts will experience higher disease rates and poorer access to care, resulting in greater incremental tooth loss. Comparison of the 2 groups at any age from the mid-20s on will show greater numbers of missing teeth in the group who were less cognitively able in childhood. Those differences will be most pronounced in old age.

Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) study.

PurposeThe purpose of this study is to evaluate an early switch to aflibecept in eyes with neovascular age-related macular degeneration (nvAMD) showing partial or lack of response for initial therapy with bevacizumab.MethodsThe Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) was a prospective, multicenter, single-arm clinical trial. Eyes with nvAMD having incomplete response to 3-9 prior bevacizumab injections were recruited. Three monthly intravitreal aflibercept (2 mg) injections were administered, followed by two bi-monthly injections and a final examination at week 28. An optional injection was allowed at week 20.ResultsForty-seven eyes of 46 patients (mean±SD age 76±8 years) were recruited. The mean number of prior bevacizumab injections was 5.5±2.9. The mean visual acuity improved from 60.3±10 ETDRS letters at baseline to 63.1±15 letters at week 28 (P=0.02, paired t-test). The central subfield thickness (CST) reduced from 409±127 micron at baseline to 330±110 microns at week 4 (P=0.0002; paired t-test), and 277±70 microns at week 28 (P=0.00002; paired t-test). Twenty-two eyes had three to five prior bevacizumab injections (mean 5.1±0.7), and 25 eyes had six to nine prior injections (7.32±1.2). Both groups had reduced CST from baseline to week 28 (P=0.0004 and P=0.0007; paired t-test, respectively). Thirty-five (75%) eyes required the optional additional aflibercept injection at week 20.ConclusionsThe ASLI study demonstrated improved BCVA and reduced CST following an early switch to aflibercept therapy in eyes with prior incomplete response to initial therapy with three to nine bevacizumab injections.

The geriatric mania asenapine study (GeMS).

RATIONALE: Population aging results in growing numbers of psychiatric disorders among older patients. Yet, there is a paucity of studies on elderly mania. OBJECTIVE: To evaluate the effect of asenapine on older manic inpatients. METHODS: Thirty-four elderly patients suffering from a manic episode, mean age 67.2 years were enrolled in an open-label 3-weeks study of asenapine treatment. INCLUSION CRITERIA: (1) DSM-IV criteria for manic episode (2) age above 60 years, (3) episode severity necessitating inpatient treatment, (4) Young Mania Rating Scale (YMRS) score at baseline >20, and (5) no prior asenapine treatment. Participants were prescribed asenapine 5 mg BID for 3 days and then dose increased to 10 mg BID till day 21 (study completion). RESULTS: Twenty-five patients completed the study. YMRS score decreased from a baseline mean of 27.0±8.8 to 13.3±12.0 at the end of the study (p<0.001). Fourteen patients (56% of completers) achieved remission (YMRS score<12). MADRS score decreased from a baseline mean of 7.6±5.6 to 4.4+5.1 at the end of the study (p<0.05); low baseline score should be noted. Sleep duration increased from a baseline median of 5.7 hours to 7.0 h at the end of the study (p<0.05). Seven patients discontinued treatment due to adverse events. Two patients passed-away after study completion. CONCLUSION: We tentatively conclude that the efficacy of asenapine in reducing acute manic symptoms and achieving remission in the elderly is supported in this study. Caution is needed in patients with co-morbid physical conditions.

Loss of inherited genomic imprints in mice leads to severe disruption in placental lipid metabolism.

INTRODUCTION: Monoallelic expression of imprinted genes is necessary for placental development and normal fetal growth. Differentially methylated domains (DMDs) largely determine the parental-specific monoallelic expression of imprinted genes. Maternally derived DNA (cytosine-5-) -methyltransferase 1o (DNMT1o) maintains DMDs during the eight-cell stage of development. DNMT1o-deficient mouse placentas have a generalized disruption of genomic imprints. Previous studies have demonstrated that DNMT1o deficiency alters placental morphology and broadens the embryonic weight distribution in late gestation. Lipids are critical for fetal growth. Thus, we assessed the impact of disrupted imprinting on placental lipids. METHODS: Lipids were quantified from DNMT1o-deficient mouse placentas and embryos at E17.5 using a modified Folch method. Expression of select genes critical for lipid metabolism was quantified with RT-qPCR. Mitochondrial morphology was assessed by TEM and mitochondrial aconitase and cytoplasmic citrate concentrations quantified. DMD methylation was determined by EpiTYPER. RESULTS: We found that DNMT1o deficiency is associated with increased placental triacylglycerol levels. Neither fetal triacylglycerol concentrations nor expression of select genes that mediate placental lipid transport were different from wild type. Placental triacylglycerol accumulation was associated with impaired beta-oxidation and abnormal citrate metabolism with decreased mitochondrial aconitase activity and increased cytoplasmic citrate concentrations. Loss of methylation at the MEST DMD was strongly associated with placental triacylglycerol accumulation. DISCUSSION: A generalized disruption of genomic imprints leads to triacylglycerol accumulation and abnormal mitochondrial function. This could stem directly from a loss of methylation at a given DMD, such as MEST, or represent a consequence of abnormal placental development.

Staff happiness and work satisfaction in a tertiary psychiatric centre.

BACKGROUND: Mental health professionals are at a high risk of burnout. Positive psychology outcomes of staff in acute in-patient psychiatric wards are poorly researched and unclear. AIMS: To quantify the satisfaction with life and work-life satisfaction of mental health staff at a large university-affiliated tertiary psychiatric centre. METHODS: We utilized the Satisfaction with Life Scale (SWLS) and the Work-Life Satisfaction Questionnaire (WLSQ). RESULTS: Two hundred and nine out of 450 staff members (46%) participated; mean age 48.2 + 9.9 years; 63% were male. On average the participants had been practising their speciality for 21.1 + 9.8 years (range: 2-48). The mean total SWLS scores differed significantly between professions (P < 0.05). The highest levels of happiness were reported by psychologists and social workers, followed by the administrative staff, the psychiatrists and finally the nursing staff. Staff scored the highest for work as a 'calling' followed by work as a 'career' and the lowest rating for work as a 'job'. The mean total WLSQ score differed between professions, (P < 0.01). The highest levels of work as a calling were reported by psychiatrists (mean 2.87 of possible 5.0), followed by psychologists and social workers, nursing staff and finally administrative staff. CONCLUSIONS: Satisfaction with life and work orientation do not correlate among mental health professionals. Although highly motivated and perceiving psychiatry as a 'calling' psychiatrists score low on levels of satisfaction with life. Improving staff happiness may contribute to increase in moral and counter burnout.

Hyperbaric oxygen-induced seizures cause a transient decrement in cognitive function.

Hyperbaric oxygen-induced seizures are classified as brief, generalized tonic-clonic seizures. They are believed to cause no residual cognitive damage, although this has not been investigated in depth. In the present study, we examined whether hyperbaric oxygen-induced seizures cause impairment of behavioral and cognitive abilities. Cognitive status was assessed using four behavioral tests: Y-maze, novel object recognition, the elevated plus maze, and a passive avoidance task. Three time intervals were examined: 24h, and 7 and 30 days after the seizures. We found transient impairment of performance in the compressed group on three tests (the novel object recognition paradigm, the Y-maze paradigm, and the passive avoidance task). On the elevated plus maze test, the impairment persisted. The time interval to the appearance of deficits and to eventual recovery was not the same for the different tests. We conclude that hyperbaric oxygen-induced seizures result in transient impairment of performance on behavioral tests in a mouse model. Further investigation is required to establish the mechanism and location of injury, and to determine whether the performance decrement on the elevated plus maze test represents permanent damage or transient damage with slow resolution. These new findings should be taken into account when planning hyperbaric oxygen treatments, to ensure that the chosen protocol is therapeutic yet minimizes the risk of CNS oxygen toxicity.

Remission amongst elderly schizophrenia patients.

Remission in elderly patients has been little studied. The present analysis utilized a European database to focus on the elderly. Using five different instruments examining remission, we report that aging did not adversely affect remission in the elderly. Management of elderly schizophrenia patients should thus be targeted towards remission.

Validation of the Multiple Sclerosis International Quality of Life questionnaire.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 +/- 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS.

Quetiapine treatment for behavioural and psychological symptoms of dementia in Alzheimer's disease patients: a 6-week, double-blind, placebo-controlled study.

SETTING: Treating elderly patients with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents. Quetiapine is an atypical antipsychotic agent that warrants further investigation. OBJECTIVES: To assess tolerability, safety, and clinical benefit of quetiapine in AD patients with BPSD. PARTICIPANTS AND DESIGN: AD patients with BPSD participated in a 6-week randomized, double-blind, placebo-controlled trial. Quetiapine was increased on the basis of clinical response and tolerability. Primary efficacy assessments included the Neuropsychiatric Inventory (NPI) and Clinical Global Impression of Change (CGI-C). Secondary efficacy measures included the Mini-Mental State Examination (MMSE), the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Forty patients (26 women), mean age 82.2 (SD 6.4) years were enrolled, 27 completed treatment. Median dose of quetiapine was 200 mg/day. Significant NPI total scores reductions (79% for placebo and 68.5% for quetiapine) were observed. The CGI-C score decreased significantly in the quetiapine group (p = 0.009 at 6 weeks) and did not change significantly in the placebo group (p = 0.48). The MMSE, AIMS, SAS scores and adverse events did not differ significantly between the two arms. CONCLUSIONS: Quetiapine did not significantly improve psychosis scores. It did not cause cognitive and motor deterioration. These results might possibly be due to small sample size.

Analysis of novel soluble chromate and uranyl reductases and generation of an improved enzyme by directed evolution.

Most polluted sites contain mixed waste. This is especially true of the U.S. Department of Energy (DOE) waste sites which hold a complex mixture of heavy metals, radionuclides, and organic solvents. In such environments enzymes that can remediate multiple pollutants are advantageous. We report here evolution of an enzyme, ChrR6 (formerly referred to as Y6), which shows a markedly enhanced capacity for remediating two of the most serious and prevalent DOE contaminants, chromate and uranyl. ChrR6 is a soluble enzyme and reduces chromate and uranyl intracellularly. Thus, the reduced product is at least partially sequestered and nucleated, minimizing the chances of reoxidation. Only one amino acid change, (Tyr)128(Asn), was responsible for the observed improvement. We show here that ChrR6 makes Pseudomonas putida and Escherichia coli more efficient agents for bioremediation if the cellular permeability barrier to the metals is decreased.

Cognitive changes in early MS: a call for a common framework.

Cognitive dysfunction is among the main symptoms of multiple sclerosis (MS) and adversely affects patients' quality of life. The occurrence of cognitive impairment early in the disease process raises crucial issues related to definition of the impairment and its magnitude as well as to the tools applied to the assessment. To date there is little evidence concerning the reliability and validity of cognitive measures in early MS and their predictive long-term role. As MS is a complex disease, multidimensional approaches should be further developed and validated to study the cognitive sphere in the early stages of the disease. Considering that none of the available tests performed in isolation is able to provide a complete picture of the cognitive impairment in early MS, this calls for the definition of phase duration, impairment and tools appropriate for use by clinicians and researches. The present review proposes a framework aimed to help neurologists in approaching cognitive impairment in early MS and stimulate discussions and evaluations of the suggested recommendations.

Effect of chromate stress on Escherichia coli K-12.

The nature of the stress experienced by Escherichia coli K-12 exposed to chromate, and mechanisms that may enable cells to withstand this stress, were examined. Cells that had been preadapted by overnight growth in the presence of chromate were less stressed than nonadapted controls. Within 3 h of chromate exposure, the latter ceased growth and exhibited extreme filamentous morphology; by 5 h there was partial recovery with restoration of relatively normal cell morphology. In contrast, preadapted cells were less drastically affected in their morphology and growth. Cellular oxidative stress, as monitored by use of an H2O2-responsive fluorescent dye, was most severe in the nonadapted cells at 3 h postinoculation, lower in the partially recovered cells at 5 h postinoculation, and lower still in the preadapted cells. Chromate exposure depleted cellular levels of reduced glutathione and other free thiols to a greater extent in nonadapted than preadapted cells. In both cell types, the SOS response was activated, and levels of proteins such as SodB and CysK, which can counter oxidative stress, were increased. Some mutants missing antioxidant proteins (SodB, CysK, YieF, or KatE) were more sensitive to chromate. Thus, oxidative stress plays a major role in chromate toxicity in vivo, and cellular defense against this toxicity involves activation of antioxidant mechanisms. As bacterial chromate bioremediation is limited by the toxicity of chromate, minimizing oxidative stress during bacterial chromate reduction and bolstering the capacity of these organisms to deal with this stress will improve their effectiveness in chromate bioremediation.

Donepezil for negative signs in elderly patients with schizophrenia: an add-on, double-blind, crossover, placebo-controlled study.

OBJECTIVE: Cognitive impairment and negative signs are common in patients with schizophrenia. Up to 35% of elderly patients with schizophrenia fulfill the diagnostic criteria of dementia. Donepezil inhibits cholinesterase, thus enhancing cholinergic neurotransmission. We tested the efficacy of donepezil in elderly patients with chronic schizophrenia and severe cognitive impairment. METHOD: Following baseline assessment, patients were randomly assigned to receive either donepezil or placebo. The dose was 5 mg daily for the first week and 10 mg for an additional 11 weeks. The procedure was repeated using the crossover compound. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI) and Alzheimer Disease Assessment Scale - Cognitive subscale (ADAS-Cog) were used to assess the severity of symptoms, cognitive status and intervention effects. RESULTS: Twenty subjects were enrolled (15 females, five males), mean age 70.2 years (SD 6.5) and mean duration of disease 38.5 years (SD 9.3). A modest treatment effect was found for both placebo and donepezil treatment periods. No crossover effect was found. No statistical differences were demonstrated between the two treatment groups (CGI p = 0.37, PANSS p = 0.71, ADAS-Cog p = 0.86). Two patients died during the study period due to unrelated causes and one patient discontinued participation due to increased agitation. CONCLUSION: Donepezil does not seem to improve negative signs and cognitive impairment in elderly patients with chronic schizophrenia.

Elderly psychiatric patients at risk of folic acid deficiency: a case controlled study.

In the elderly, folic acid deficiency may result in psychiatric symptoms or the increases in severity of other organic and non-organic mental diseases. We aimed to characterize elderly, community-dwelling, newly admitted patients to a large urban psychiatric hospital who are suffering from untreated folic acid deficiency in comparison with elderly inpatients who do not suffer from this deficiency. During a 2-year period, all subjects aged 65 years or older admitted to the large psychiatric center were tested for levels of serum folic acid levels. Subjects suffering from folic acid deficiency were compared (unpaired t-test) with matched patients with normal serum levels. Of the 293 newly admitted elderly patients 45 (15.7%) suffered from folic acid deficiency. Mean age for the folic acid deficient group was 77.3+/-8.1 years, 38% were diagnosed as suffering from dementia, 22% were depressed and 51% were living alone. In the comparison group mean age was 77.3+/-6.3 years, 33% were diagnosed as suffering from dementia, 24% were suffering from depression and 57% were living alone. We conclude that we could not find any "characteristic" of elderly subjects at risk of folic acid deficiency.

Cognitive patterns and progression in multiple sclerosis: construction and validation of percentile curves.

BACKGROUND AND OBJECTIVES: Rate and pattern of progression of cognitive decline in multiple sclerosis (MS) has not been clearly identified. The present study aimed to identify correlations between cognitive tests and disease duration, construct longitudinal cognitive curves, and assess pattern of change over time. METHODS: The Neuropsychological Screening Battery for Multiple Sclerosis was administered in 150 consecutive MS patients, and tests that correlated with disease duration were identified. Percentile curves were constructed and the pattern of cognitive decline over time explored. The cognitive curves were validated in an additional group of 83 patients with MS. RESULTS: Three of four measures of the spatial recall test (SPART 7/24), and the paced auditory serial addition task for two seconds (PASAT 2'), correlated with disease duration. These tests were used to construct cross-sectional curves identifying the pattern of cognitive decline over time in the MS population. On the basis of this cross-sectional analysis, the earliest cognitive decline occurred in the SPART 7/24 trials 1-5 between one and three years from onset, followed by decline in the SPART delayed recall between three and seven years, and then by decline in the PASAT 2' after seven years from onset. CONCLUSIONS: Verbal fluency and verbal memory appear to be affected earliest in MS. The pattern of cognitive decline is further characterised by a decrease in visuospatial learning, followed by delayed recall, and then by attention and information processing speed. Cognitive percentile curves can be used to evaluate the pattern of progression and identify patients at increased risk.

T cell vaccination in multiple sclerosis relapsing-remitting nonresponders patients.

Myelin autoreactive T cells are involved in the pathogenesis of multiple sclerosis (MS) and lead to propagation of the disease. We evaluated the efficacy of T cell vaccination (TCV) therapy for patients with aggressive relapsing-remitting MS who failed to respond to immunomodulatory treatments. Twenty nonresponders relapsing-remitting MS patients were immunized with autologous attenuated T cell lines after activation with synthetic myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) encephalitogenic peptides. Each patient received three vaccinations in 6- to 8-week intervals. Annual relapse rate decreased from 2.6 to 1.1, P = 0.026. Neurological disability stabilized as compared with the 2- and 1-year pretreatment progression rates. Significant reduction in the number and volume of active lesions, as well as reduction in T2 lesion burden, was demonstrated by quantitative MRI analysis. No serious adverse events were observed. Our findings suggest that TCV has beneficial clinical effects in MS patients who, in spite of immunomodulatory treatments, continue to deteriorate. TCV could serve as a potential alternative therapy for this subgroup of nonresponders patients.

Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients.

Anticholinergic medication (ACM) is frequently used in psychiatry to treat the side-effects of D2 blocking agents. However, ACM is not without adverse effects and, in the elderly, cognitive and memory impairments have been emphasized. The aim of this study was to evaluate the effects of discontinuation of ACM on cognitive functions in a group of elderly chronic schizophrenia patients. Twenty-seven elderly patients (age 60 years or older), who were diagnosed as suffering from schizophrenia (DSM-IV) and receiving ACM in addition to antipsychotic treatment, were enrolled. Before and after ACM was discontinued, the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale was administered. Twenty-one patients completed the study. All were receiving Akineton (biperiden), 2-6 mg daily before the study. Significant improvement in the ADAS-Cog total score was demonstrated (P < 0.03), as well as in the ideational praxia and orientation subscales. Improvement was correlated with the previous dose of biperidin. No adverse events or emergent extrapyramidal symptoms were noted. Discontinuation of ACM may be warranted in chronic schizophrenia patients since it may improve cognitive functioning with no adverse effects.

Suicidality and second generation antipsychotics in schizophrenia patients: a case-controlled retrospective study during a 5-year period.

RATIONALE: Rates of attempted suicide for individuals with schizophrenia are approaching 30%. Attempted suicide is among the most potent predictors of subsequent suicide. Several studies suggest that suicide is more likely to occur in patients who are not being adequately treated or not being treated at all. An effort was made in the last decade to evaluate the antisuicide effects of pharmacological treatment in schizophrenia with emphasis on the role of the newer second-generation antipsychotics (SGA). OBJECTIVE: The aim of the present study was to assess in a large cohort of schizophrenia patients the effects of exposure to SGA on suicidality of patients suffering from schizophrenia or schizoaffective disorder. The study is a retrospective case-controlled evaluation over a 5-year period undertaken in a large university affiliated tertiary care psychiatric hospital. METHODS: Between January 1998 and December 2002, all records of admissions of schizophrenia or schizoaffective disorder patients (ICD-10) were assessed. Data as to age, gender, diagnosis, suicide attempt prior to admission, treatment with antipsychotic medication, dose and duration of treatment (mg daily, duration) with SGA was extracted from patients' files. All patients who had attempted suicide prior to admission were defined as the index group. The case-controlled group was comprised of the next admission of a patient suffering from schizophrenia (or schizoaffective disorder), matched for gender and age, who did not attempt suicide. RESULTS: Records of 756 patients (4486 admissions for said period) were analyzed (56.6% male, mean age 39.1+/-13.5 years). Amongst 378 patients who attempted suicide (index group), 16.1% were exposed to SGA while 37% were exposed in the control group (P=0.0001). The protective effect (odds ratio) of treatment by SGA was 3.54 (95%CI: 2.4-5.3). Risperidone was more frequently prescribed in the control group (54.3%) and had a larger effect-size than olanzapine (3.16 versus 1.76), although not statistically significant. Clozapine was prescribed only to a few patients. CONCLUSIONS: Schizophrenia patients exposed to both risperidone and olanzapine may gain protection from suicidality. The antisuicide effects seem to differ between SGAs. The long duration and large sample size support this finding, despite the retrospective nature of this study.

Cognitive impairment in probable multiple sclerosis.

OBJECTIVES: To evaluate and characterise cognitive impairment in the very early stage of multiple sclerosis (MS), in which patients are still diagnosed as suffering from probable MS. METHODS: The Brief Repeatable Battery-Neuropsychological (BRB-N) that has been validated for MS patients was used. Abnormal performance was defined as one standard deviation below the mean reported for healthy age matched subjects. Neurological disability and brain magnetic resonance imaging (MRI) were performed for all patients. Correlation coefficients were calculated between disease burden variables and performance on the BRB-N. RESULTS: Sixty seven patients with probable MS were evaluated within a mean of one month of the onset of new neurological symptoms. Evidence for the presence of cognitive impairment was shown in 53.7% of patients. Verbal abilities and attention span were most frequently affected. Impairment was not correlated with neurological disability or MRI disease burden. CONCLUSION: Prevalent cognitive impairment already exists at onset of MS.