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BACKGROUND Olfactory impairment is an early symptom of Alzheimer disease (AD). However, it is rarely assessed in clinical practice. This study aimed to assess the identification and discrimination of specific odors in patients with early-stage AD using the Sniffin' Sticks test and determine the items that would be most valuable in the diagnosis of early-stage AD in order to create a brief test of olfactory dysfunction. MATERIAL AND METHODS Three groups of participants were enrolled, including 30 patients with mild cognitive impairment due to AD (MCI-AD group), 30 with mild dementia due to AD (MD-AD group), and 30 older participants with normal cognition (NC group). All participants underwent cognitive (Clinical Dementia Rating, Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale, and verbal fluency tests) and olfactory (Burghart Sniffin' Sticks odor identification and odor discrimination tests) assessments. RESULTS The MD-AD group scored significantly lower than the MCI-AD group and the MCI-AD group scored significantly lower than the NC group in both the odor identification (P<0.001) and discrimination (P<0.05) tasks. The shortened versions of the odor identification and discrimination tasks showed good diagnostic properties in differentiating patients with AD from the NC participants (receiver operating characteristic [ROC] area under the curve [AUC]=0.912 and 0.954, respectively) and differentiating patients with MCI-AD from the NC participants (ROC AUC=0.871 and 0.959, respectively). CONCLUSIONS The brief versions of olfactory tests, containing selected items that were found to differ the most between cognitively normal participants and early-stage AD patients, have good diagnostic qualities and can aid clinicians in screening for early-stage AD.

Odor identification (OI) is impaired in the early stages of Alzheimer's disease (AD). However, data regarding the diagnostic properties of OI tests are lacking, preventing their clinical use. We aimed to explore OI and determine the accuracy of OI testing in screening for patients with early AD. In total, 30 participants with mild cognitive impairment due to AD (MCI-AD), 30 with mild dementia due to AD (MD-AD), and 30 cognitively normal elderly participants (CN) were enrolled, and cognitive examination (CDR, MMSE, ADAS-Cog 13, and verbal fluency tests) and assessment of OI (Burghart Sniffin' Sticks odor identification test) were performed. MCI-AD patients scored significantly worse in OI than CN participants, and MD-AD patients had worse OI scores than MCI-AD patients. The ratio of OI to ADAS-Cog 13 score had good diagnostic accuracy in differentiating AD patients from CN participants and in differentiating MCI-AD patients from CN participants. Substitution of ADAS-Cog 13 score with the ratio of OI to ADAS-Cog 13 score in a multinomial regression model improved the classification accuracy, especially of MCI-AD cases. Our results confirmed that OI is impaired during the prodromal stage of AD. OI testing has a good diagnostic quality and can improve the accuracy of screening for early-stage AD., (© 2023. The Author(s).)

Background: Olfactory dysfunction is an early symptom of Alzheimer's disease (AD). However, olfactory tests are rarely performed in clinical practice because their diagnostic efficacy in detecting early AD is unclear., Objective: To investigate odor discrimination in patients with early AD and the efficacy of olfactory discrimination tests in differentiating these patients from subjects with normal cognition (CN)., Methods: Thirty patients each with mild dementia due to AD (MD-AD) and mild cognitive impairment due to AD (MCI-AD) and 30 older subjects with CN were enrolled. All participants underwent cognitive examinations (CDR, MMSE, ADAS-Cog 13, and verbal fluency) and odor discrimination tests (Sniffin' Sticks test, Burghart®, Germany)., Results: The MD-AD group achieved significantly worse scores on the olfactory discrimination test than the MCI-AD group, and the MCI-AD group achieved significantly worse results than the CN group (p < 0.05). A cut-off score of≤10 had a diagnostic accuracy of 94.44% (95% CI, 87.51-98.17%) in differentiating patients with MCI-AD/MD-AD from subjects with CN and of 91.67% (95% CI, 81.61-97.24%) in differentiating those with MCI-AD from subjects with CN. Our multinomial logistic regression model with demographic data and ADAS-Cog 13 scores as predictor variables correctly classified 82.2% of the cases (CN, 93.3%; MC-AD, 70%; MD-AD, 83.3%); on adding the olfactory discrimination score to the model, the percentage increased to 92.2% (CN, 96.7%; MCI-AD, 86.7%; MD-AD, 93.3%)., Conclusion: Odor discrimination is impaired in cases of early AD and continues to deteriorate as the disease progresses. The olfactory discrimination test showed good diagnostic efficacy in detecting early AD.

The aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (MS) patients. In single-center prospective study patients who failed to conventional therapies for highly active relapsing MS underwent the AHSCT. The disability was followed up with Expanded Disability Status Scale and cognition with Brief International Cognitive Assessment for Multiple Sclerosis. Twenty four patients [18 (72.0%) female] underwent AHSCT. Two patients of 13 had one relapse during the first year and three patients-during the second year after AHSCT. Disability regression was found in 84.6% of patients. The scores of information processing speed and verbal learning were significantly higher at month 12 after AHSCT. The clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT. No transplant related-deaths were observed. Selective cognitive improvement was found after AHSCT in MS patients. The disability may be temporarily reversible after AHSCT in a significant proportion of highly active RMS patients if AHSCT is well-timed performed.

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 AND 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., Competing Interests: Conflicts of interests The authors have no conflicts of interest to declare.

Introduction. Recent studies demonstrate relationship between type of multiple sclerosis (MS) and cognitive dysfunction (CD). It is also known that cognitive dysfunction depends on the other factors such as number of demyelinated lesions and local atrophy detected in brain magnetic resonance imaging (MRI). At the very beginning of the disease cognitive alterations might be the only markers indicating impairment in MS. Progression in cognitive dysfunction despite stable values calculated according Expanded disability status scale, EDSS, shows MS progression itself, therefore studies in this field are very relevant. Different patterns of cognitive alterations and their expression in relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) are revealed. Determination in cognitive and MRI markers differences between RRMS and SPMS could be helpful in distinguishing forms of MS additionally in clinical examination. Despite stability in physical examination, progression in CD shows that MS treatment potentially is not enough effective and requires revision in selection of disease modifying therapy more effective as possible. Goals. In this study we sought to compare patients having relapsing-remitting (RR) MS to those having secondary-progressive (SP) MS with respect to congnitive impairments and investigate the relationship of cognitive dysfunction with linear MRT markers, number of lesions and as well as type of MS. Methods. The study involved 43 patients with established RR (mean age 33.65±9.24) and 45 patients with established SP (47.82±7.72) MS. All patients were investigated in Vilnius University hospital "Santariškių klinikos". Inclusion criteria were as follows: MS diagnosis established according McDonalds revisited 2005 criteria, compatible with reviewed McDonalds 2010 criteria, concomitant diseases were excluded, patients did not used antidepressants and anxiolythics during one month period. In order to assess cognitive functions the cognitive tests battery was applied. Working memory was tested by performing Digit Span Forwards Test (DSf), speed of psychomotor reactions was detected by using Digital Symbol Substitution Test (DSST), Trail Making Test A (TMT A), frontal functions were tested by Trail Making Test B (TMT B), Five Point Test (FPT), Letter Fluency Test (DAS), Category fluency Test, verbal memory - Rey Auditory Verbal Learning Test (RAVLT), visual memory - Rey-Osterrieth Complex Figure Test (ROCFT). Brain MRI T2W and T1W lesion load was calculated. Linear MRI parameters to measure local atrophy were applied: width of third ventricle, bicaudatus index, bifrontal index, Hucmann index, index of frontal atrophy, Evans index and index of corpus callosum. Results. Comparison of RR and SP groups with respect to congnitive function has shown that there were differences with respect to all tests but* DSF test (4.88±0.98 (RR) vs 5.20±3.47 (SP); p=0.478). Comparison with respect to linear MRT markers did not produce difference only in case of bifrontal index (1.86±0.23 (RR) vs 1.86±0.22 (SP); p = 0.978). Looking for the best predictor of type of MS results were as follows. In case of cognitive tests the best predictive ability was demonstrated by RAVLT4 (area under receiver operator curve = 0.884; p<0.001) and DSST (area under receiver operator curve = 0.873; p<0.001) whereas in case of linear MRT markers bicaudalus index was the most informative one (area under receiver operator curve = 0.864; p<0.001). Cognitive function tests correlated with MRT markers (maximal correlation was observed between DSST and bicaudalus index: r=-0.570 (p<0.001)) as well as number of MRI lesions (maximal correlation was observed with TMTA: r=0.339 (p<0.001) however binary variable indicating MS type was most frequently retained in stepwise linear regression models for prediction of cognitive dysfunction by MRT markers, number of lesions and MS type. Conclusions. Our results confirm that cognitive dysfunction in MS are related to linear MRT markers, number of lesions and type of MS, however in SPMS the alterations are expresssed more. Slowing in verbar learning, speed of psychomotor reactions and decreased attention are the mostly affected domains of CD in MS. Rey Auditor Verbal Learning Test, RAVLT(4), and Digital Symbol Substitution Test, DSST, are the most prominent tests when distinguishing between RRMS and SPMS forms. Linear MRT marker bicaudalus index was the most informative in discrimination between RR and SP MS forms. [ABSTRACT FROM AUTHOR]

Background. Multiple sclerosis (MS) is an inflammatory demyelinating disorder of central nervous system that is the major course of the disability of young adults. Cognitive dysfunction has negative impact on patients' daily activities, their ability to work, drive, maintain normal social relationships and therefore significantly worsen the patient's quality of life. Patients and methods. A prospective research was performed in Vilnius University Hospital Santariskiu Klinikos Centre of Neurology in 2010 - the first study assessing cognitive function in patients with multiple sclerosis, using an automated computerized neuropsychological test battery CANTAB (Cambridge Neuropsychological Test Automated Battery). There were 20 subjects with clinical definite MS and 20 healthy control subjects participating (>18 years old). Every subject was given CANTAB (Cambridge Neuropsychological Test Automated Battery) tests, evaluating choice response speed, spatial planning, spatial working memory, episodic memory, remembering and working memory capacity. Four cognitive tests were performed: choice reaction time (CRT), spatial span (SSP), Stockings of Cambridge (SOC) and Paired Associates Learning. Results. Choice reaction time: patients 0.431±0.106426 seconds, healthy controls 0.303±0.046620 seconds (p-value 0,000). Healthy persons have made an average of 0.45±0.686 errors per 100, patients have made 1.6± 1.818 errors per 100 (p-value = 0.012). Attention capacity: for patients 5.2±0.696 objects and 6.6± 1.095 objects for healthy controls (p = 0.000). Problems, solved with minimum number of turns: patients 6.74±2.207 problems, healthy controls - 8.15±2.159 problems (p = 0.051). Movements of the figures used to solve problems at all levels: for patients - 18.9868±2.50205 movements, for healthy controls with average 17.2875±2.05560 movements (p = 0.026). Number of errors made in PAL test: patients have made 35.45±38.627 errors, healthy persons 12.55±25.938 errors (p = 0.034). How many of the tasks solved correctly the first time in the PAL test: patients the first time solved 4.95±1.317 tasks, healthy persons 6.35±1.089 tasks (p = 0.001). The total number of times the test was repeated before PAL test was solved correctly: patients 17.1±6.561 times, healthy persons - 11.5±4.059 (p = 0.002). Number of boxes correctly showed immediately after the first presentation in the PAL test: patients - 15.70±5.069, healthy controls - 20.80±3.679 (p = 0.001). The strongest negative statistically significant correlation between EDSS value and attention capacity (correlation coefficient -0.522, p-value = 0.001). Statistically significant negative correlation seen between physical disability and this criterion - the number of tasks correctly solved the first time in the PAL test (correlation coefficient -0.477, p-value = 0.002). The strongest statistically significant correlation seen between duration of disease and reaction rate (r = 0.414, p = 0.008), attention capacity (r = - 0.395, P = 0.012) and the number of tasks correctly solved the first time in the PAL test (r = -0.400, P = 0.011). Conclusions: 1) Cognitive functions in MS patients are significantly worse than in the control group. 2) Cognitive functions rates significantly correlated with physical disability (EDSS scores). The strongest correlation was with attention capacity and speed of reaction. 3) Duration of the disease correlates with these cognitive functions: reaction speed, attention capacity and some rates of episodic memory (there is no strong correlation); duration of disease has no correlation with frontal functions. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is a major course of disability inpatients with multiple sclerosis (MS). The prevalence of cognitivedys-function (CD) is estimated up to 65% MS patients. Natural history studies suggest that CD develops early in MS even in a clinically isolated syndrome and it is not likely to remit. Patients with MS who have cognitive impairment most commonly display deficits in the cognitive domains of memory, learning, attention, and information processing. In diagnosing CD in a patient with MS, it is important first to recognize and to treat the common comorbidities of fatigue, anxiety and, depression. The article describes physical and CD correlations with magneticresonance imaging (MTI) parameters: T2 burdenlesion, T1 "black holes", and brain atrophy. The value of whole brain atrophy and regional brain atrophy is reviewed. Newer imaging techniques to evaluate potential relation ships between cognitive dysfunction and brain pathology are described. Magnetization transfer imaging (MTI), diffusion tensor MRI (DT-MRI), positronemission tomography (PET), single-photonemission tomography (SPET), functional MRI (fMRI), and MR spectroscopy are the methods providing additional valuable information about brain pathology and its correlations with cognitive tests. MRI techniques provide specific information and ideally should be used for monitoring MS evolution, physical and cognitive disability as well. Data from longitudinal studies concerning MS progression is presented. The article provides results from two pilot crossectional studies performed in Vilnius University hospital Santariškiūklinikos Department of Neurology concerning CD in MS and relationship between brain MRI focal changes, parameters of brain atrophy and disability. Routine cognitive testing would be helpful to evaluate CD. As worsening cognitive impairment may indicate progressive disease course in the absent of increasing physical disability, individual MS patient monitoring and the treatment to delay disease progression and cognitive decline progression is obligatory also. [ABSTRACT FROM AUTHOR]