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Background/Aim. In accordance with modern trends of organizing specialized service dealing with dementia, the first memory clinic in Serbia ? Center for memory disorders and dementia was established in 2008 in Belgrade at Neurology Clinic ? Clinical Center of Serbia (CCS) as a university-affiliated outpatient clinic for subjects with cognitive impairment and dementia. The aim of this report was to outline the frequency of diagnosis, sociodemographic and medical characteristics of patients referring to the Center for memory disorders and dementia. Methods. The sample consisted of patients registered between 2008 and 2016 who underwent comprehensive and specialized diagnostic procedures in the Center. Results. A total of 3,873 visits were made for 2,198 patients, 39.6% of which proceed to annually follow-up visits. The majority of the sample (65.3%) was women. The mean age was 69.8 ? 12.1 years (range 29?89 years) and the average education level was 12.1 ? 3.3 years. Of this total number, at the moment of the first visit, 44.4% of the patients were fulfill criteria for Mild cognitive impairment (MCI), 28.2% had dementia due to Alzheimer?s disease (AD), 7.8% had dementia secondary to a vascular pathology (VaD), 7.3% had frontotemporal dementia (FTD), 0.6% had dementia with Lewy bodies (DLB), and 1.7% had dementia due to Parkinson's disease (PDD). The mean Mini Mental test score in the whole sample was 22.6 ? 6.8 points. Conclusion. The data collected through the activity of the Center enabled an insight into the demographic and medical characteristics of patients, as well as planning further activities in the health care system. The systemic introduction of more standardized diagnostic practices, establishing and networking of similar centers will improve the accuracy and rate of dementia diagnosis in the Serbian population.

Myotonic dystrophy type 2 (DM2) is a slowly progressive, autosomal-dominant disease. This is a multisystemic disorder that affects the heart, which is one of the main causes of morbidity and mortality in DM2. The aim of the study was to define cardiac impairments in patients with DM2 and its association with sociodemographic and clinical features of patients. This retrospective study comprised 62 adult patients with DM2 hospitalized at the Neurology Clinic, Clinical Center of Serbia from 2013 until 2018, who underwent electrocardiography (ECG) and echocardiography examinations. Hypertension was observed in 42% of DM2 patients. One-fifth of DM2 patients had bradycardia, while other conduction and rhythm impairments were rare. Only one patient had a pacemaker implanted because of the first degree AV block associated with incomplete left bundle branch block. Echocardiography showed diastolic dysfunction of the left ventricle in 44% of patients, while systolic dysfunction was found in only 4%. Cardiomyopathy was observed in 18% of patients, of whom three-fourth had dilated type. Cardiac conduction and rhythm defects are relatively rare in DM2, while diastolic dysfunction is common. This suggests that regular ECG and echocardiography screening is needed in DM2. Adequate therapy should be introduced in patients with DM2 on time to reduce the frequency of heart complications and to prevent premature death.

Objectives: Frontotemporal dementia (FTD) is the second most common form of degenerative dementia in early onset dementia (EOD) patients. The core disorders in the FTD spectrum are: behavioral variant of FTD (FTDbv) with predominant early changes in behavior (such are disinhibition, apathy, loss of empathy, compulsive behaviour..); and language variants - primary progressive aphasias (PPA) where language is the primary impairment (difficulties in speech, understanding, repetition..). Patients with sporadic, as well as genetic forms of FTD, can develop motor symptoms of motor neuron disease (before, after or at the same time with cognitive/behavioural features) or atypical parkinsonism-progressive supranuclear palsy or corticobasal syndrome, which are all part of the clinical FTD spectrum. The FTD is still poorly recognised entity and the heterogeneity of clinical presentations, early onset (most frequently before the age of 65), as well as overlap of early FTDbv symptoms and psychiatric diseases, often results in wrong diagnosis and presents a challenge, even in tertiary referral centres. It has been shown that delay in correct dementia diagnosis contributes to the caregiver's and patient's distress. The early and precise diagnosis is important for consideration of prognosis and course of the disease with family members; possibilities of improving patient's quality of life by giving them adequate symptomatic therapy; guiding the genetic analysis which is especially important for family members who also could be in risk of carring or passing the mutation to their offspring. Aim: In this mini review paper we tried to point out the specificity of clinical manifestation in the FTD spectrum, which could be helpful in making the early and accurate diagnosis among the variety of EOD cases. Conclusion: Early and accurate FTD diagnosis is important for the insight of the disease course, giving adequate symptomatic therapy and guiding the genetic analysis which reduces the caregiver's and patient's distress.

This study identified structural and functional brain connectivity alterations in two independent samples of patients along the posterior cortical atrophy (PCA) disease course. Twenty-one PCA patients and 44 controls were recruited from two expert centres. Microstructural damage of white matter (WM) tracts was assessed using probabilistic tractography; resting state (RS) functional connectivity of brain networks was explored using a model free approach; grey matter (GM) atrophy was investigated using voxel-based morphometry. Compared with controls, common patterns of damage across PCA patients included: GM atrophy in the occipital-temporal-parietal regions; diffusion tensor (DT) MRI alterations of the corpus callosum and superior (SLF) and inferior longitudinal fasciculi (ILF) bilaterally; and decreased functional connectivity of the occipital gyri within the visual network and the precuneus and posterior cingulum within the default mode network (DMN). In PCA patients with longer disease duration and greater disease severity, WM damage extended to the cingulum and RS functional connectivity alterations spread within the frontal, dorsal attentive and salience networks. In PCA, reduced DMN functional connectivity was associated with SLF and ILF structural alterations. PCA patients showed distributed WM damage. Altered RS functional connectivity extends with disease worsening from occipital to temporo-parietal and frontostriatal regions, and this is likely to occur through WM connections. Future longitudinal studies are needed to establish trajectories of damage spreading in PCA and whether a combined DT MRI/RS functional MRI approach is promising in monitoring the disease progression., Highlights • PCA patients showed distributed WM damage. • In PCA, WM damage is associated with longer disease duration ad greater severity. • In PCA, altered RS functional connectivity extends with disease worsening.

Background: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant disease. One third of DM1 patients die suddenly, most of them due to the heart conduction abnormalities and arrhythmias. The aim of this study was to analyze echocardiographic findings in a large cohort of DM1 patients. Methods: This retrospective study comprised 111 patients and 71 healthy controls (HCs) matched for gender and age. Results: Mitral valve (MV) prolapse was observed in 23% of our DM1 patients vs. 8.5% of HCs (p 0.05). Systolic dysfunction was more common in patients with severe electrocardiographic (ECG) abnormality (18.8% vs. 2.7%, p

Neuropsychological examinations in myotonic dystrophy (DM) patients show a great variability of results from a condition of intellectual disability to the subtle cognitive impairments. It is unclear if different clusters of neuropsychological deficits appear in different phenotypes of DM, or if there are patients with no cognitive deficit at all. The aim of this study is to assess cognitive impairments among patients with different phenotypes of DM type 1 (DM1) and type 2 (DM2), and to potentially define cognitive clusters in these disorders. Study comprised 101 DM1 and 46 DM2 adult patients who were genetically confirmed. Patients underwent analysis of five cognitive domains (visuospatial, executive, attention, memory and language). Virtually all DM1 patients had cognitive defect with approximately 2-3 cognitive domains affected. On the other hand, one-third of DM2 patients had completely normal neuropsychological findings, and in other two-thirds approximately 1-2 domains were affected. Cluster analysis showed that in both diseases visuospatial and executive dysfunctions seemed to be the main cognitive defects, while memory and language impairments appeared in more severe phenotypes. Our results showed that a single form of DM1 or DM2 may consist of several cognitive clusters. Understanding of cognitive impairments in DM is very important to follow positive and side effects in ongoing and future clinical trials.

Background: Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia (EOD), characterized by behavioral changes (behavioral variant; bvFTD) or language deficits. A hexanucleotide repeat expansion in a noncoding region of chromosome 9 open reading frame 72 (C9orf72) has been proved to be a major cause of both familial and sporadic amyotrophic lateral sclerosis or FTD, with or without concomitant motor neuron disease (MND). Methods: The aim of this study was to assess the frequency of the C9orf72 hexanucleotide expansion in a cohort of 117 Serbian patients with EOD and to report phenotypic features of identified carriers. Results: We identified 4 of 117 (3.4%) patients with EOD to have C9orf72 hexanucleotide expansions. All patients were classified in the FTD disease spectrum group (8.2%): 3 patients fulfilled the criteria for bvFTD, and 1 patient had FTD-MND. None of the patients with the C9orf72 hexanucleotide expansion fulfilled the diagnostic criteria for language variants of FTD, FTD-progressive supranuclear palsy overlap syndrome, dementia with Lewy bodies or Alzheimer's dementia. Conclusion: In a cohort of consecutive patients with EOD, 3.4% had the C9orf72 hexanucleotide expansion with clinical phenotypes of bvFTD or an overlap of bvFTD and MND.

This prospective study explored whether an approach combining structural [cortical thickness and white matter (WM) microstructure] and resting state functional MRI can aid differentiation between 62 early onset Alzheimer's disease (EOAD) and 27 behavioural variant of frontotemporal dementia (bvFTD) patients. Random forest and receiver operator characteristic curve analyses assessed the ability of MRI in classifying the two clinical syndromes. All patients showed a distributed pattern of brain alterations relative to controls. Compared to bvFTD, EOAD patients showed bilateral inferior parietal cortical thinning and decreased default mode network functional connectivity. Compared to EOAD, bvFTD patients showed bilateral orbitofrontal and temporal cortical thinning, and WM damage of the corpus callosum, bilateral uncinate fasciculus, and left superior longitudinal fasciculus. Random forest analysis revealed that left inferior parietal cortical thickness (accuracy 0.78, specificity 0.76, sensitivity 0.83) and WM integrity of the right uncinate fasciculus (accuracy 0.81, specificity 0.96, sensitivity 0.43) were the best predictors of clinical diagnosis. The combination of cortical thickness and DT MRI measures was able to distinguish patients with EOAD and bvFTD with accuracy 0.82, specificity 0.76, and sensitivity 0.96. The diagnostic ability of MRI models was confirmed in a subsample of patients with biomarker-based clinical diagnosis. Multiparametric MRI is useful to identify brain alterations which are specific to EOAD and bvFTD. A severe cortical involvement is suggestive of EOAD, while a prominent WM damage is indicative of bvFTD., Highlights • Multimodal MRI distinguishes in vivo EOAD and bvFTD patients • EOAD and bvFTD show a distributed pattern of structural brain alterations • A severe cortical involvement is suggestive of EOAD relative to bvFTD • A prominent WM damage is indicative of bvFTD relative to EOAD

Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD). The aim of this study was to estimate the correlates of NPS in patients with PD in the initial motor stage of the disease (hemiparkinsonism). A total of 111 patients with PD and 105 healthy control participants were assessed. Patients with PD experienced apathy, depression, and anxiety more frequently compared with healthy controls. Sleep disturbances occurred commonly in early PD patients. Patients with PD and mild cognitive impairment (MCI) had depression and anxiety more frequently, but not apathy, compared with patients with PD without MCI. The results of this study confirm a high burden of NPS even in the earliest motor stage of PD.

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia (EOD), characterized by behavioral changes (behavioral variant; bvFTD) or language deficits. A hexanucleotide repeat expansion in a noncoding region of chromosome 9 open reading frame 72 (C9orf72) has been proved to be a major cause of both familial and sporadic amyotrophic lateral sclerosis or FTD, with or without concomitant motor neuron disease (MND).The aim of this study was to assess the frequency of the C9orf72 hexanucleotide expansion in a cohort of 117 Serbian patients with EOD and to report phenotypic features of identified carriers.We identified 4 of 117 (3.4%) patients with EOD to have C9orf72 hexanucleotide expansions. All patients were classified in the FTD disease spectrum group (8.2%): 3 patients fulfilled the criteria for bvFTD, and 1 patient had FTD-MND. None of the patients with the C9orf72 hexanucleotide expansion fulfilled the diagnostic criteria for language variants of FTD, FTD-progressive supranuclear palsy overlap syndrome, dementia with Lewy bodies or Alzheimer's dementia.In a cohort of consecutive patients with EOD, 3.4% had the C9orf72 hexanucleotide expansion with clinical phenotypes of bvFTD or an overlap of bvFTD and MND.

The aim of this study was to assess cognitive status in a large group of patients with myotonic dystrophy type 2 (DM2) compared to type 1 (DM1) subjects matched for gender and age, using a comprehensive battery of neuropsychological tests. Thirty-four genetically confirmed adult DM2 patients were recruited and matched for gender and age with 34 adult-onset DM1 subjects. All patients underwent detailed classic pen and pencil neuropsychological investigation and also computerized automated battery—CANTAB. More than half of DM2 patients had abnormal results on executive tests [Intra/Extradimensional Set Shift (IED), Stockings of Cambridge (SOC)] and verbal episodic memory (Ray Auditory Verbal Learning Test). Regarding DM1, abnormal results in more than 50 % of subjects were achieved in even ten tests, including visuospatial, language, executive, cognitive screening and visual memory tests. Direct comparison between patient groups showed that lower percentage of DM2 patients had abnormal results on following tests: Addenbrooke’s Cognitive Examination—Revised, Raven Standard Progressive Matrices, Block Design, copy and recall of Rey-Osterieth Complex Figure, number of categories and perseverative responses on Wisconsin Card Sorting Test and Boston Naming Test (p < 0.01), as well as Trail Making Test—B and Spatial Span (p < 0.05). Our results showed significant dysexecutive syndrome and certain impairment of episodic verbal memory in DM2 patients that are reflective of frontal (especially frontostriatal) and temporal lobe dysfunction. On the other hand, dysexecutive and visuospatial/visuoconstructional deficits predominate in DM1 which correspond to the frontal, parietal (and occipital) lobe dysfunction.