Browsing by Author "Stojković, Tanja (57211211787)"

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. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Cognitive loading aggravates the freezing of gait (FoG), which is observed in approximately 50% of patients with Parkinson's disease (PD) in the advanced stages. To investigate whether a specific pattern of executive deficits, that is, attentional set-shifting and/or inhibitory control, are associated with FoG in PD, 30 PD patients with FoG (PD-FoG+) and 36 PD patients without FoG (PD-FoG-) and 22 control healthy subjects were examined with a comprehensive neuropsychological battery. Intra-Extra Dimensional Set shifting Test (IED) and Stop Signal Task (SST), selected from the Cambridge Automated Neuropsychological Battery (CANTAB battery), were administered to analyze set-shifting and motor inhibition, respectively. The IED task was significantly sensitive for differentiating between PD-FoG+ and PD-FoG- groups (p<.01), as well Adenbrook's clock drawing task (p=.033). By contrast, no differences emerged on any aspect of the SST task and other cognitive tasks. The attrition rate during the IED task showed that the problem in the PD-FoG+ group appeared at the pre-ID level, on the discrimination-learning set; the 32% PD-FoG+ subjects did not achieve the ID level of the task in comparison to negligible 4% of the PD-FoG- patients (p=.011). The logistic regression analysis, indicated the higher the IED stage successfully completed, the less likely presence of FoG in PD subjects. These results demonstrate that the complex cognitive-motor interplay might be responsible for FoG in PD and have had real life implication for the patients. Copyright © 2014 The International Neuropsychological Society.

Cognitive loading aggravates the freezing of gait (FoG), which is observed in approximately 50% of patients with Parkinson's disease (PD) in the advanced stages. To investigate whether a specific pattern of executive deficits, that is, attentional set-shifting and/or inhibitory control, are associated with FoG in PD, 30 PD patients with FoG (PD-FoG+) and 36 PD patients without FoG (PD-FoG-) and 22 control healthy subjects were examined with a comprehensive neuropsychological battery. Intra-Extra Dimensional Set shifting Test (IED) and Stop Signal Task (SST), selected from the Cambridge Automated Neuropsychological Battery (CANTAB battery), were administered to analyze set-shifting and motor inhibition, respectively. The IED task was significantly sensitive for differentiating between PD-FoG+ and PD-FoG- groups (p<.01), as well Adenbrook's clock drawing task (p=.033). By contrast, no differences emerged on any aspect of the SST task and other cognitive tasks. The attrition rate during the IED task showed that the problem in the PD-FoG+ group appeared at the pre-ID level, on the discrimination-learning set; the 32% PD-FoG+ subjects did not achieve the ID level of the task in comparison to negligible 4% of the PD-FoG- patients (p=.011). The logistic regression analysis, indicated the higher the IED stage successfully completed, the less likely presence of FoG in PD subjects. These results demonstrate that the complex cognitive-motor interplay might be responsible for FoG in PD and have had real life implication for the patients. Copyright © 2014 The International Neuropsychological Society.

Background: Whether connectome mapping of structural and functional connectivity across the brain could be used to predict patterns of atrophy progression in patients with mild Parkinson disease (PD) has not been well studied. Purpose: To assess the structural and functional connectivity of brain regions in healthy controls and its relationship with the spread of gray matter (GM) atrophy in patients with mild PD. Materials and Methods: This prospective study included participants with mild PD and controls recruited from a single center between January 2012 and December 2023. Participants with PD underwent three-dimensional T1-weighted brain MRI, and the extent of regional GM atrophy was determined at baseline and every year for 3 years. The structural and functional brain connectome was constructed using diffusion tensor imaging and resting-state functional MRI in healthy controls. Disease exposure (DE) indexes—indexes of the pathology of each brain region—were defined as a function of the structural or functional connectivity of all the connected regions in the healthy connectome and the severity of atrophy of the connected regions in participants with PD. Partial correlations were tested between structural and functional DE indexes of each GM region at 1- or 2-year follow-up and atrophy progression at 2- or 3-year follow-up. Prediction models of atrophy at 2- or 3-year follow-up were constructed using exhaustive feature selection. Results: A total of 86 participants with mild PD (mean age at MRI, 60 years ± 8 [SD]; 48 male) and 60 healthy controls (mean age at MRI, 62 years ± 9; 31 female) were included. DE indexes at 1 and 2 years were correlated with atrophy at 2 and 3 years (r range, 0.22–0.33; P value range, .002–.04). Models including DE indexes predicted GM atrophy accumulation over 3 years in the right caudate nucleus and some frontal, parietal, and temporal brain regions (R2 range, 0.40–0.61; all P < .001). Conclusion: The structural and functional organization of the brain connectome plays a role in atrophy progression in the early stages of PD. © RSNA, 2024.

[No abstract available]

[No abstract available]

Introduction: Impulsive compulsive behaviors (ICBs) in Parkinson’s disease (PD) are debilitating disorders of repetitive, excessive, and compulsive nature affecting up to one third of PD patients. Objectives are to address clinical, psychiatric, and cognitive characteristics of ICBs and to define risk factors in PD patients in the initial motor stage, followed up for 5 years. Methods: We analyzed 106 consecutive PD outpatients at Hoehn and Yahr disease stage 1 and 125 healthy controls. The participants were assessed for the presence of any ICB using the current clinical criteria and underwent comprehensive clinical, psychiatric, and neuropsychological evaluations. The patients completed the same protocol at Years 1, 2, 3, and 5. Results: ICBs were present in 21 (19.8%) PD patients and 13 (10.4%) healthy controls at baseline. Prevalence of ICBs increased to 29.2% at Year 5, significantly after Year 2. Multiple ICBs were present in 4,7% and 61.9% of PD-ICBs at the baseline and Year 5, respectively. ICBs resolved in 30% of cases (most often compulsive eating). Dopamine agonist treatment at the baseline carried five times higher risk of having or developing ICB(s) anytime during follow-up. We identified risk factors for compulsive eating (dopamine agonist treatment at baseline), hypersexuality (males), compulsive buying (depression and younger age), and punding (younger age and higher levodopa dose at baseline). Significant interaction of rate of motor progression and ICB diagnosis was shown. Conclusions: PD patients showed increasing frequency of most ICBs during the 5-year follow-up. Specific risk factors were identified for different types of ICBs. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: Impulsive compulsive behaviors (ICBs) in Parkinson’s disease (PD) are debilitating disorders of repetitive, excessive, and compulsive nature affecting up to one third of PD patients. Objectives are to address clinical, psychiatric, and cognitive characteristics of ICBs and to define risk factors in PD patients in the initial motor stage, followed up for 5 years. Methods: We analyzed 106 consecutive PD outpatients at Hoehn and Yahr disease stage 1 and 125 healthy controls. The participants were assessed for the presence of any ICB using the current clinical criteria and underwent comprehensive clinical, psychiatric, and neuropsychological evaluations. The patients completed the same protocol at Years 1, 2, 3, and 5. Results: ICBs were present in 21 (19.8%) PD patients and 13 (10.4%) healthy controls at baseline. Prevalence of ICBs increased to 29.2% at Year 5, significantly after Year 2. Multiple ICBs were present in 4,7% and 61.9% of PD-ICBs at the baseline and Year 5, respectively. ICBs resolved in 30% of cases (most often compulsive eating). Dopamine agonist treatment at the baseline carried five times higher risk of having or developing ICB(s) anytime during follow-up. We identified risk factors for compulsive eating (dopamine agonist treatment at baseline), hypersexuality (males), compulsive buying (depression and younger age), and punding (younger age and higher levodopa dose at baseline). Significant interaction of rate of motor progression and ICB diagnosis was shown. Conclusions: PD patients showed increasing frequency of most ICBs during the 5-year follow-up. Specific risk factors were identified for different types of ICBs. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Most of the heritability in frontotemporal dementia (FTD) is accounted for by autosomal dominant hexanucleotide expansion in the chromosome 9 open reading frame 72 (C9orf72), pathogenic/likely pathogenic variants in progranulin (GRN), and microtubule-associated protein tau (MAPT) genes. Until now, there has been no systematic analysis of these genes in the Serbian population. Herein, we assessed the frequency of the C9orf72 expansion, pathogenic/likely pathogenic variants in GRN and MAPT in a well-characterized group of 472 subjects (FTD, Alzheimer’s disease - AD, mild cognitive impairment - MCI, and unspecified dementia - UnD), recruited in the Memory Center, Neurology Clinic, University Clinical Center of Serbia. The C9orf72 repeat expansion was detected in 6.98% of FTD cases (13.46% familial; 2.6% sporadic). In the UnD subgroup, C9orf72 repeat expansions were detected in 4.08% (8% familial) individuals. Pathogenic variants in the GRN were found in 2.85% of familial FTD cases. Interestingly, no MAPT pathogenic/likely pathogenic variants were detected, suggesting possible geographical specificity. Our findings highlight the importance of wider implementation of genetic testing in neurological and psychiatric practice managing patients with cognitive-behavioral and motor symptoms. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

Most of the heritability in frontotemporal dementia (FTD) is accounted for by autosomal dominant hexanucleotide expansion in the chromosome 9 open reading frame 72 (C9orf72), pathogenic/likely pathogenic variants in progranulin (GRN), and microtubule-associated protein tau (MAPT) genes. Until now, there has been no systematic analysis of these genes in the Serbian population. Herein, we assessed the frequency of the C9orf72 expansion, pathogenic/likely pathogenic variants in GRN and MAPT in a well-characterized group of 472 subjects (FTD, Alzheimer’s disease - AD, mild cognitive impairment - MCI, and unspecified dementia - UnD), recruited in the Memory Center, Neurology Clinic, University Clinical Center of Serbia. The C9orf72 repeat expansion was detected in 6.98% of FTD cases (13.46% familial; 2.6% sporadic). In the UnD subgroup, C9orf72 repeat expansions were detected in 4.08% (8% familial) individuals. Pathogenic variants in the GRN were found in 2.85% of familial FTD cases. Interestingly, no MAPT pathogenic/likely pathogenic variants were detected, suggesting possible geographical specificity. Our findings highlight the importance of wider implementation of genetic testing in neurological and psychiatric practice managing patients with cognitive-behavioral and motor symptoms. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

Introduction: Clinical correlates of autonomic nervous system (ANS) dysfunction in early Parkinson's disease (PD) have been addressed mainly in a cross-sectional way. Methods: This is a combined cross-sectional and longitudinal prospective study of ANS dysfunction using the SCOPA-AUT in PD patients at the Hoehn and Yahr stage 1 with disease duration <2 years. PD patients (n = 107) were compared to healthy controls (HC, n = 79), and then followed-up for over 3 years. The severity of PD, depression, anxiety, apathy and cognitive impairment were evaluated using rating scales. Results: At least one symptom of ANS dysfunction was present in 71% of PD patients in comparison to 30.4% of HC, and in all PD patients after three years. The overall severity of dysautonomia symptoms was mild (SCOPA-AUT mean ± SD; 4.16 ± 5.0), but worsened by 23%, 86% and 0.3% during the 1st, 2nd and 3rd year respectively. Nighttime voiding (38.3%), constipation (30.8%) and straining for defecation (29%) were the most common symptoms. Prevalence and severity of urinary, gastrointestinal, and orthostatic symptoms increased, in contrast to thermoregulatory and pupillomotor symptoms. Frequency of symptoms suggestive of multi-domain ANS dysfunction rose from 49% to 79%. Psychiatric symptoms and age, but not motor impairment, were associated with dysautonomia symptoms. Conclusion: Symptoms of ANS dysfunction were frequent in the initial motor stage of PD and progressed, yet remaining mild, within 3 years. An independent progression of dysautonomia symptoms from motor disability and its associations with non-motor, mainly psychiatric symptoms and age support the non-motor clustering in PD. © 2019 Elsevier Ltd

Introduction: Clinical correlates of autonomic nervous system (ANS) dysfunction in early Parkinson's disease (PD) have been addressed mainly in a cross-sectional way. Methods: This is a combined cross-sectional and longitudinal prospective study of ANS dysfunction using the SCOPA-AUT in PD patients at the Hoehn and Yahr stage 1 with disease duration <2 years. PD patients (n = 107) were compared to healthy controls (HC, n = 79), and then followed-up for over 3 years. The severity of PD, depression, anxiety, apathy and cognitive impairment were evaluated using rating scales. Results: At least one symptom of ANS dysfunction was present in 71% of PD patients in comparison to 30.4% of HC, and in all PD patients after three years. The overall severity of dysautonomia symptoms was mild (SCOPA-AUT mean ± SD; 4.16 ± 5.0), but worsened by 23%, 86% and 0.3% during the 1st, 2nd and 3rd year respectively. Nighttime voiding (38.3%), constipation (30.8%) and straining for defecation (29%) were the most common symptoms. Prevalence and severity of urinary, gastrointestinal, and orthostatic symptoms increased, in contrast to thermoregulatory and pupillomotor symptoms. Frequency of symptoms suggestive of multi-domain ANS dysfunction rose from 49% to 79%. Psychiatric symptoms and age, but not motor impairment, were associated with dysautonomia symptoms. Conclusion: Symptoms of ANS dysfunction were frequent in the initial motor stage of PD and progressed, yet remaining mild, within 3 years. An independent progression of dysautonomia symptoms from motor disability and its associations with non-motor, mainly psychiatric symptoms and age support the non-motor clustering in PD. © 2019 Elsevier Ltd

Background: White matter hyperintensities (WMHs) have a role in cognitive impairment in normal brain aging, while the effect on Parkinson's disease (PD) progression is still controversial. Objective: To investigate the longitudinal evolution of micro- and macrostructural damage of cerebral white matter (WM) and its relationship with the clinical picture in PD. Methods: A total of 154 PD patients underwent clinical, cognitive, and magnetic resonance imaging (MRI) assessment once a year for up to 4 years. Sixty healthy controls underwent the same protocol at baseline. WMHs were identified and total WMH volume was measured. WMHs were also used as exclusion masks to define normal-appearing white matter (NAWM). Using tract-based spatial statistics, diffusion tensor (DT) MRI metrics of whole-brain WM and NAWM were obtained. Linear mixed-effects models defined the longitudinal evolution and association between variables. WM alterations were tested as risk factors of disease progression using linear regression and Cox proportional hazards models. Results: At baseline, PD patients showed alterations of all DT MRI measures compared to controls. Longitudinally, DT MRI measures did not vary significantly and no association with clinical variables was found. WMH volume changed over time and was associated with impairment in global cognition, executive functions, and language. Baseline WMH volume was a moderate risk factor for progression to mild cognitive impairment. Conclusions: Our study suggests an association between WMHs and cognitive deterioration in PD, whereas WM microstructural damage is a negligible contributor to clinical deterioration. WMHs assessed by MRI can provide an important tool for monitoring the development of cognitive impairment in PD patients. © 2021 International Parkinson and Movement Disorder Society. © 2021 International Parkinson and Movement Disorder Society.

Background: White matter hyperintensities (WMHs) have a role in cognitive impairment in normal brain aging, while the effect on Parkinson's disease (PD) progression is still controversial. Objective: To investigate the longitudinal evolution of micro- and macrostructural damage of cerebral white matter (WM) and its relationship with the clinical picture in PD. Methods: A total of 154 PD patients underwent clinical, cognitive, and magnetic resonance imaging (MRI) assessment once a year for up to 4 years. Sixty healthy controls underwent the same protocol at baseline. WMHs were identified and total WMH volume was measured. WMHs were also used as exclusion masks to define normal-appearing white matter (NAWM). Using tract-based spatial statistics, diffusion tensor (DT) MRI metrics of whole-brain WM and NAWM were obtained. Linear mixed-effects models defined the longitudinal evolution and association between variables. WM alterations were tested as risk factors of disease progression using linear regression and Cox proportional hazards models. Results: At baseline, PD patients showed alterations of all DT MRI measures compared to controls. Longitudinally, DT MRI measures did not vary significantly and no association with clinical variables was found. WMH volume changed over time and was associated with impairment in global cognition, executive functions, and language. Baseline WMH volume was a moderate risk factor for progression to mild cognitive impairment. Conclusions: Our study suggests an association between WMHs and cognitive deterioration in PD, whereas WM microstructural damage is a negligible contributor to clinical deterioration. WMHs assessed by MRI can provide an important tool for monitoring the development of cognitive impairment in PD patients. © 2021 International Parkinson and Movement Disorder Society. © 2021 International Parkinson and Movement Disorder Society.

We investigated the diagnostic accuracy of brainstem MRI measurements in patients with different progressive supranuclear palsy (PSP) syndromes and Parkinson's disease (PD). Using 3D T1-weighted images, midbrain, and pons areas, as well as superior (SCP) and middle cerebellar peduncle (MCP) widths were measured in 10 patients with Richardson's syndrome (PSP-RS), 10 patients with PSP-parkinsonism (PSP-P), 25 patients with PD, and 24 healthy controls. The ratio between pons and midbrain areas (pons/midbrain), that between MCP and SCP widths (MCP/SCP), and the MR parkinsonism index ([pons/midbrain]*[MCP/SCP]) were calculated. The pons/midbrain and the MR parkinsonism index allowed to differentiate PSP-RS from PD with high sensitivity (90%, 100%), specificity (96%, 92%), and accuracy (94%, 97%). Only the pons/midbrain was found to distinguish PSP-P from PD, but with a lower diagnostic accuracy (sensitivity = 60%, specificity = 96%, accuracy = 86%). Compared to PSP-RS, PSP-P experience a relatively less severe involvement of infratentorial brain. The pons/midbrain looks as a promising measure in the differentiation of individual PSP-P from PD patients. © 2010 Movement Disorder Society.

We investigated the diagnostic accuracy of brainstem MRI measurements in patients with different progressive supranuclear palsy (PSP) syndromes and Parkinson's disease (PD). Using 3D T1-weighted images, midbrain, and pons areas, as well as superior (SCP) and middle cerebellar peduncle (MCP) widths were measured in 10 patients with Richardson's syndrome (PSP-RS), 10 patients with PSP-parkinsonism (PSP-P), 25 patients with PD, and 24 healthy controls. The ratio between pons and midbrain areas (pons/midbrain), that between MCP and SCP widths (MCP/SCP), and the MR parkinsonism index ([pons/midbrain]*[MCP/SCP]) were calculated. The pons/midbrain and the MR parkinsonism index allowed to differentiate PSP-RS from PD with high sensitivity (90%, 100%), specificity (96%, 92%), and accuracy (94%, 97%). Only the pons/midbrain was found to distinguish PSP-P from PD, but with a lower diagnostic accuracy (sensitivity = 60%, specificity = 96%, accuracy = 86%). Compared to PSP-RS, PSP-P experience a relatively less severe involvement of infratentorial brain. The pons/midbrain looks as a promising measure in the differentiation of individual PSP-P from PD patients. © 2010 Movement Disorder Society.

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. © 2017 The Authors

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. © 2017 The Authors

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. © 2016 American Psychiatric Association. All rights reserved.

[No abstract available]