Gintaras Kaubrys

The decay of memory between delayed and long-term recall in patients with temporal lobe epilepsy

OBJECTIVES Impairment of long-term recall may worsen everyday functioning of patients with epilepsy even if the standard short-term or delayed recall tests do not show significant abnormalities. We evaluated prospectively the decay of memory between delayed and long-term recall in patients with temporal lobe epilepsy (TLE) and controls with the aim of identifying the determinants of long-term memory impairment. METHODS Seventy patients with TLE and 59 controls underwent neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions at visit 1. Long-term verbal and nonverbal memory was tested with the same word list, verbal logical story, and Rey-Osterrieth complex figure test 4 weeks later at visit 2. The decay in memory was estimated as information recalled at visit 2 as a percentage of the delayed recall at visit 1. RESULTS Frequent seizures (> or = 4 per month) during the study period were related to poor long-term recall, even for those patients who did relatively well on delayed recall tests. On all long-term memory tests, patients with complex partial and/or secondary generalized seizures did significantly worse than patients with simple partial seizures. The presence of interictal generalized or focal temporal epileptiform activity was associated with more accelerated forgetting of the word list and complex figure. Multiple regression analysis confirmed that number of complex partial seizures, age of patient, and abnormal interictal EEG are significant predictors of accelerated forgetting. CONCLUSIONS Uncontrolled seizures, especially with ictal impairment of consciousness, can be a significant factor in the accelerated decay of memory, although subclinical interictal epileptiform EEG activity may also be relevant.

Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years

Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained.

The BICAMS Battery for Assessment of Lithuanian-Speaking Multiple Sclerosis Patients: Relationship with Age, Education, Disease Disability, and Duration

Background Assessment of cognitive impairment (CI) in multiple sclerosis (MS) patients is very useful, but it requires time-consuming expert evaluation with specialized materials. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was created as a brief and specific instrument for the evaluation of CI. The aims of this study were to assess the cognitive status of MS patients by using the Lithuanian version of BICAMS, to evaluate the test-retest reliability of the Lithuanian version of BICAMS, and to measure the impact of CI on disability and duration of MS. Material/Methods We enrolled 50 MS patients and 20 cognitively normal control subjects, matched for age, gender, and level of education. Cognitive functions were assessed by the BICAMS tests, which include the Symbol Digit Modalities Test, the Brief Visuospatial Memory Test Revised, and the California Verbal Learning Test, 2nd edition. Results MS patients performed significantly worse than controls on the 3 neuropsychological tests of BICAMS (p<0.001). Younger and intellectually employed persons performed significantly better on these tests than older persons, manual workers, or unemployed persons (p<0.05). MS patients with higher disability scores tended to perform worse on the tests (p<0.05), but we found no relationship between BICAMS test scores and the duration of the disease or relapse rate (p>0.05). Test-retest reliability was excellent for all 3 subtests (r>0.8, p<0.05). Conclusions Our study shows that BICAMS is a valid and acceptable cognitive assessment tool that can be recommended for routine use in Lithuania for assessing patients with MS.

Dementia and Art: Neuronal Intermediate Filament Inclusion Disease and Dissolution of Artistic Creativity

The paper presents a new case of neuronal intermediate filament inclusion disease (NIFID), a recently described new variant of early-onset frontotemporal dementia. Documented with repetitive brain images, morphologically proven cases additionally endorse evolving the clinical and pathological phenotype of NIFID. For the first time the paper describes the probable influence of NIFID on the artistic creativity of an accomplished artist showing rapid dissolution of artistic talent.

Selective Ability of Some CANTAB Battery Test Measures to Detect Cognitive Response to a Single Dose of Donepezil in Alzheimer Disease

Background The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to explore which tests and their measures are able to detect cognitive change after a single dose of donepezil in Alzheimer disease (AD) patients. The aim of this study was to establish the ability of CANTAB tests and their measures to detect cognitive change after a single 5-mg dose of donepezil in treatment-naïve AD patients. Material/Methods We enrolled 62 treatment-naïve AD patients and 30 healthy controls in this prospective, randomized, rater-blinded study. AD patients were randomized to 2 groups: the AD+ group received donepezil after the first CANTAB testing and the AD− group remained treatment-naïve at second testing. The time period between repeated testing was 4 hours. Parallel versions of CRT, SOC, PAL, SWM, and PRM tests were used. Results All groups did not differ according to age, education, gender, or depression (p>0.05). AD+ and AD− groups did not differ according to MMSE. SOC, PAL, PRM, and SWM tests distinguished AD from controls. Eight measures of PAL and PRM had a strong correlation with MMSE (r>0.7). Repeated-measures ANOVA with Bonferroni post-hoc test showed the difference of change in AD+ and AD− groups between first and second CANTAB testing in 7 PAL measures. AD+ and AD− groups differed in the second testing by 7 PAL measures. Four PAL measures differed in first and second testing within the AD+ group. Conclusions The CANTAB PAL test measures, able to detect cognitive change after a single dose of donepezil in AD patients, are: PAL mean trials to success, total errors (adjusted), total errors (6 shapes, adjusted), and total trials (adjusted).

Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients

Background Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naïve and on stable donepezil treatment, matched by age, education, sex, and cognitive function. Material/Methods We recruited 22 consecutive treatment-naïve AD patients (AD-N group), 22 AD patients treated with a stable donepezil dose of 10 mg/day for at least 3 months (AD-T group), and 50 healthy controls were recruited. Neuropsychological testing (MMSE, ADAS-Cog, and additional tests) and ERP recording was performed and analyzed. Results All groups did not differ according to age, duration of education, or sex (p>0.05). AD-N and AD-T groups did not differ according to cognitive function. The AD-T group had longer duration of disease than the AD-N group (p<0.001). The AD-T and AD-N groups did not differ in P300 latencies (p=0.49). N200 latency was longer in the AD-T group (p<0.001). The general linear model showed that significant predictors of P300 latency were age (p=0.019) and AD treatment status (p<0.001). Duration of AD was a significant predictor of N200 latency (p=0.004). Conclusions The response of N200 latency to donepezil treatment differs from the response of P300. P300 is a better marker of ChEI treatment-dependent cognitive functions. N200 is more dependent on the duration of AD.

Specific Features of Executive Dysfunction in Alzheimer-Type Mild Dementia Based on Computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) Test Results

Background The primary manifestation of Alzheimer’s disease (AD) is decline in memory. Dysexecutive symptoms have tremendous impact on functional activities and quality of life. Data regarding frontal-executive dysfunction in mild AD are controversial. The aim of this study was to assess the presence and specific features of executive dysfunction in mild AD based on Cambridge Neuropsychological Test Automated Battery (CANTAB) results. Material/Methods Fifty newly diagnosed, treatment-naïve, mild, late-onset AD patients (MMSE ≥20, AD group) and 25 control subjects (CG group) were recruited in this prospective, cross-sectional study. The CANTAB tests CRT, SOC, PAL, SWM were used for in-depth cognitive assessment. Comparisons were performed using the t test or Mann--Whitney U test, as appropriate. Correlations were evaluated by Pearson r or Spearman R. Statistical significance was set at p<0.05. Results AD and CG groups did not differ according to age, education, gender, or depression. Few differences were found between groups in the SOC test for performance measures: Mean moves (minimum 3 moves): AD (Rank Sum=2227), CG (Rank Sum=623), p<0.001. However, all SOC test time measures differed significantly between groups: SOC Mean subsequent thinking time (4 moves): AD (Rank Sum=2406), CG (Rank Sum=444), p<0.001. Correlations were weak between executive function (SOC) and episodic/working memory (PAL, SWM) (R=0.01–0.38) or attention/psychomotor speed (CRT) (R=0.02–0.37). Conclusions Frontal-executive functions are impaired in mild AD patients. Executive dysfunction is highly prominent in time measures, but minimal in performance measures. Executive disorders do not correlate with a decline in episodic and working memory or psychomotor speed in mild AD.

Cognitive Results of CANTAB Tests and Their Change Due to the First Dose of Donepezil May Predict Treatment Efficacy in Alzheimer Disease

Background Ability to predict the efficacy of treatment in Alzheimer disease (AD) may be very useful in clinical practice. Cognitive predictors should be investigated alongside with the demographic, genetic, and other predictors of treatment efficacy. The aim of this study was to establish whether the baseline measures of CANTAB tests and their changes due to the first donepezil dose are able to predict the efficacy of treatment after 4 months of therapy. We also compared the predictive value of cognitive, clinical, and demographic predictors of treatment efficacy in AD. Material/Methods Seventy-two AD patients (62 treatment-naïve and 10 donepezil-treated) and 30 controls were enrolled in this prospective, randomized, rater-blinded, follow-up study. Treatment-naïve AD patients were randomized to 2 groups to take the first donepezil dose after the first or second CANTAB testing, separated by 4 hours. Follow-up Test 3 was performed 4 months after the initial assessment. Results The groups were similar in age, education, gender, Hachinski index, and depression. General Regression Models (GRM) have shown that cognitive changes after the first dose of donepezil in PAL (t-values for regression coefficients from 3.43 to 6.44), PRMd (t=4.33), SWM (t=5.85) test scores, and baseline results of PAL (t=2.57–2.86), PRM (t=3.08), and CRT (t=3.42) tests were significant predictors of long-term donepezil efficacy in AD (p<0.05). Conclusions The cognitive changes produced by the first donepezil dose in CANTAB PAL, PRM, and SWM test measures are able to predict the long-term efficacy of donepezil in AD. Baseline PAL, PRM, and CRT test results were significant predictors.

Cognition During and After Multiple Sclerosis Relapse as Assessed With the Brief International Cognitive Assessment for Multiple Sclerosis

There is some evidence that cognition may be impaired during multiple sclerosis (MS) relapse. The aims of this study were to assess the cognitive status with the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in MS patients during relapse, in stable patients, and in healthy controls; to evaluate cognitive changes up to 3 months after relapse; and to estimate the impact of different factors on cognition after relapse. BICAMS was performed in 60 relapsing, 30 stable patients and 30 controls. Relapsing MS patients were assessed during relapse and one and three months after relapse. SDMT score was lower in relapsing than in stable patients. The mean scores of all BICAMS tests were higher one month after relapse than during relapse (p < 0.001). SDMT score after relapse improved in younger patients, who had more severe relapse (p < 0.05). BVMT-R score improved more in men, in patients with biologically active interferon-beta, in patients treated with methylprednisolone and in patients who were rehabilitated (p < 0.05). CVLT-II score improved in women and in patients with shorter relapse (p < 0.05). A neuropsychological assessment, like the evaluation of physical disability, is important during relapse. BICAMS may be suitable for a quick and effective assessment of cognition during relapse.

Composite Marker of Cognitive Dysfunction and Brain Atrophy is Highly Accurate in Discriminating Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis.

Background With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. Material/Methods We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. Results Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. Conclusions The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS.