Women are disproportionately affected by Alzheimer's Disease (AD), with sex being the second strongest risk factor after age. Consequently, over 65% of people with late-onset AD are women. Therefore, a preventative approach is especially important in the female population. Cognitive reserve (CR) is recognized as a strong protective factor against AD. Its importance for cognitive functioning is reflected by the fact not taking it into account can have a clinical implication of lack of good randomization and unwanted skewing of clinical trial results. The studies exploring relationships between CR and cognitive performance in healthy female population are scarce. This study aimed to explore the differences in cognitive functioning in working-age women with different levels of CR. A total of 114 healthy female volunteers aged 30-65 years were recruited among employees of the University of Belgrade. The exclusion criteria included conditions affecting communicative ability and/or safe engagement in the interventions, as well as the presence of any neurological, psychiatric, medical condition or iatrogenic cause known to affect the brain structure and/or function. All participants underwent a detailed assessment including basic demographic data, vascular risk factors, mood scales and comprehensive neuropsychological assessment as well as Cognitive Reserve Index Questionnaire (CRIq). Statistical analysis was performed using SPSS20. The mean age of our subjects was 48.11±0.80 years with mean education of 19.01±0.39 years. CRI levels were classified as medium (28.1%), medium-high (34.2%), and high (37.7%). Regarding neuropsychological testing, significant differences were found on tests of category fluency ( p  = 0.002) and visuospatial domain including visual memory (Rey–Osterrieth complex figure copy ( p  = 0.002), spatial recognition memory percent correct ( p  = 0.023), rapid visual processing ( p  = 0.026)), with the group with the lowest CRI having the poorest results. These differences withhold correction for age. CR interacts with cognitive abilities even at working age in women. This interaction is most significant in domains that are predominantly affected in AD. These results support the theory of strong protective effect of CR in this at-risk population. Opportunities for CR development are especially important in female gender and should be tailored into preventative AD strategies.

Over 65% of people with late-onset Alzheimer's Disease (AD) are women. It is hypothesized that the higher rate of AD in women compared to men may be because women are more negatively affected by some of the known AD risk factors, particularly apolipoprotein E e4 allele (+APOE-e4). We recruited 114 healthy female volunteers aged 30-65 years among employes of the Belgrade University. The exclusion criteria were conditions affecting communicative ability and/or safe engagement in the interventions, as well as presence of any neurological, psychiatric, medical condition or iatrogenic cause known to affect the brain structure and/or function. All participants underwent a detailed assessment including basic demographic data, data on vascular risk factors, mood scales and comprehensive neuropsychological assessment as well as Cognitive Reserve Index Questionnaire (CRIq). Statistical analysis was done using SPSS20. Average age of all participants was 48,15±8,41 and average years of education was 19,02. In this cohort, which included 27 APOE4 heterozygotes, 2 homozygotes, and 85 non-carriers. Since there were only 2 homozygotes, we compared heterozygotes to non-carriers. Heterozygotes had a mean age of 46.27±7.91, and non-carriers had a mean age of 48,54±8.62. No significant differences were observed when compared neuropsychological measures by domain (i.e., attention, working memory, executive functions, verbal and visual memory, visuospatial and language functions). We did not find differences in cognitive performance in healthy working-age females regarding their APOE4 carrier status. More research is needed on this kind off cohorts especially with APOE4 homozygous to better understand the onset of cognitive disturbances connected with APOE polymorphism.

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are recognized as a spectrum of neurodegenerative disorders with overlapping clinical, pathological, and genetic features. The identification of C9orf72 hexanucleotide repeat expansion as the most common genetic cause of both conditions has prompted further investigation of genetic modifiers that may contribute to disease heterogeneity. We aimed to analyze the frequency of C9orf72 repeat expansions and potential modifying roles of APOE, ATXN1, and ATXN2 in Serbian ALS/FTD patients. Methods: Our study included an ALS/FTD cohort (n = 22) and healthy controls (n = 94). Repeat sizing in C9orf72, ATXN1 and ATXN2 was performed by fluorescent polymerase chain reaction (PCR) and capillary electrophoresis, while repeat-primed PCR was used to confirm C9orf72 expansions. APOE genotyping was conducted using real-time PCR assays targeting SNPs rs429358 and rs7412. Results: In the ALS/FTD cohort, 31.82% of the patients had heterozygous C9orf72 repeat expansion. The most common APOE genotype among patients was ε3/ε3 (72.73%). Intermediate-length ATXN1 alleles (32–44 repeats) were detected in 13.64% of patients and ATXN2 intermediate-length alleles (27–33 repeats) were found in 9% of patients. No significant differences were observed between ALS/FTD patients and controls in APOE ε4 frequency or intermediate ATXN1/ATXN2 repeats. Conclusions: Larger, population-specific studies and meta-analyses are needed to better understand the role of genetic modifiers in ALS/FTD pathogenesis and their influence on clinical heterogeneity. By integrating genetic and clinical data, this study represents a step toward the development of precision medicine strategies for ALS/FTD.

Following the COVID-19 pandemic, a shift from traditional in-person conferences to virtual and hybrid formats was welcomed for its accessible, cost-effective approach to sharing scientific knowledge and connecting people. Here, we discuss an effective hybrid format that combines in-person and online elements to foster inclusivity by providing a flexible, cost-effective alternative to in-person meetings.

β-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer’s disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinicians of the European Alzheimer’s Disease Consortium (EADC) discuss the critical relevance of introducing these new treatments in clinical care now. Given the complexity of AD it is unlikely that molecular single-target treatments will achieve substantially larger effects than those seen with current β-amyloid-targeting antibodies. Larger effects will most likely only be achieved incrementally by continuous optimization of molecular approaches, patient selection and combinations therapies. To be successful in this regard, drug development must be informed by the use of innovative treatments in real world practice, because full understanding of all facets of novel treatments requires experience and data of real-world care beyond those of clinical trials. Regarding the antibodies under discussion we consider their effects meaningful and potential side effects manageable. We assume that the number of eventually treated patient will only be a fraction of all early AD patients due to narrow eligibility criteria and barriers of access. We strongly endorse the use of these new compound in clinical practice in selected patients with treatment documentation in registries. We understand this as a critical step in advancing the field of AD treatment, and in shaping the health care systems for the new area of molecular-targeted treatment of neurodegenerative diseases.

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 Supplemental material is available for this article. See also the editorial by Yamada in this issue.

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.

Background and Objectives Data on care home admission and survival rates of patients with syndromes associated with frontotemporal lobar degeneration (FTLD) are limited. However, their estimation is essential to plan trials and assess the efficacy of intervention. Population-based registers provide unique samples for this estimate. The aim of this study was to assess care home admission rate, survival rate, and their predictors in incident patients with FTLD-associated syndromes from the European FRONTIERS register-based study. Methods We conducted a prospective longitudinal multinational observational registry study, considering incident patients with FTLD-associated syndromes diagnosed between June 1, 2018, and May 31, 2019, and followed for up to 5 years till May 31, 2023. We enrolled patients fulfilling diagnosis of the behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS), and FTD with motor neuron disease (FTD-MND). Kaplan-Meier analysis and Cox multivariable regression models were used to assess care home admission and survival rates. The survival probability score (SPS) was computed based on independent predictors of survivorship. Results A total of 266 incident patients with FTLD were included (mean age +/- SD = 66.7 +/- 9.0; female = 41.4%). The median care home admission rate was 97 months (95% CIs 86-98) from disease onset and 57 months (95% CIs 56-58) from diagnosis. The median survival was 90 months (95% CIs 77-97) from disease onset and 49 months (95% CIs 44-58) from diagnosis. Survival from diagnosis was shorter in FTD-MND (hazard ratio [HR] 4.59, 95% CIs 2.49-8.76, p < 0.001) and PSP/CBS (HR 1.56, 95% CIs 1.01-2.42, p = 0.044) compared with bvFTD; no differences between PPA and bvFTD were found. The SPS proved high accuracy in predicting 1-year survival probability (area under the receiver operating characteristic curve = 0.789, 95% CIs 0.69-0.87), when defined by age, European area of residency, extrapyramidal symptoms, and MND at diagnosis. Discussion In FTLD-associated syndromes, survival rates differ according to clinical features and geography. The SPS was able to predict prognosis at individual patient level with an accuracy of similar to 80% and may help to improve patient stratification in clinical trials. Future confirmatory studies considering different populations are needed.

To decipher the mechanisms of network-based neurodegeneration in Parkinson's disease (PD) investigating the relationship between functional connectivity (FC) in healthy connectome and grey matter (GM) atrophy accumulation in mild PD patients, and to develop a predictive model for atrophy spreading in PD.

In preparation for the approval of new therapies for Alzheimer's disease (AD), a key step is the selection, validation and application of screening tests for disease detection and treatment monitoring. Biomarkers for AD have significantly advanced the field in several ways and hold promise for early diagnosis, determination of pathology, and measurement of response to treatment. The classic pathophysiological features of AD (beta-amyloid Ab (A), tau (T) and neurodegeneration (N) can be determined in the cerebrospinal fluid (CSF), but their presence can also be demonstrated by different imaging techniques such as Positron Emission Tomography (PET), either with an amyloid marker or with tau-ligand as the gold standards of amyloid and tau pathology, in trials in clinical practice. Currently, there are no widely accepted blood tests for neuroinflammation, astrocytic, microglial activation in AB. However, both methods are either invasive and/or very expensive at the same time, so great efforts have been made to determine basic and more specific biomarkers in blood as a less invasive and more accessible procedure. In the primary health care setting, diagnostic algorithms from blood could already be sufficient to improve the accuracy of the clinical diagnosis of AB dementia and to positively influence the future treatment and care of people with cognitive problems. Additional studies are needed to evaluate the optimal combination of plasma biomarkers with other accessible and cost-effective procedures, such as, for example, MRI and cognitive tests, which are necessary for further development of predictive algorithms, which will be especially important in non-demented patients with cognitive problems.

Over the last decades, the interdisciplinary field of the affective sciences has seen proliferation rather than integration of theoretical perspectives. This is due to differences in metaphysical and mechanistic assumptions about human affective phenomena (what they are and how they work) which, shaped by academic motivations and values, have determined the affective constructs and operationalizations. An assumption on the purpose of affective phenomenacan be used as a teleological principle to guide the construction of a common set of metaphysical and mechanistic assumptions—a framework for human affective research. In this capstone paper for the special issue “Towards an Integrated Understanding of the Human Affectome”, we gather the tiered purpose of human affective phenomena to synthesize assumptions that account for human affective phenomenacollectively. This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

Introduction: Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is clinically manifested by the development of dementia. Studies of genetic susceptibility to AD indicate a whole range of genes and their variants that can potentially influence an individual's susceptibility to develope the disease. AD17 represents a form of Alzheimer's disease associated with mutation(s) in the TREM2 gene, encoding triggering receptor expressed on myeloid cells 2. The aim of this study was to determine the frequency of R47H variant of the TREM2 gene in the population of AD patients, to compare the frequency of the variant in the population of AD patients and the control group, and to determine a possible association of a certain genotype with susceptibility to AD. Material and Methods: The study included 168 consecutive patients with AD and 190 healthy controls. The clinical inerview, neurologic examination, and neuropsychological set of cognitive assessment were performed by neurologists and neuropsychologists in expertise with neurodegenerative deseases. Genotyping of rs75932628, R47H polymorphism of the TREM2 gene was performed using Real-time Polymerase Chain Reaction and TaqMan® SNP genotyping assay (Applied Biosystem by Thermo Fisher Scientific, USA) according to the manufacturer's recommendations. Results: In the group of AD patients the frequency of C allele was 98.8%, while the T allele was present in 1.2% of patients. The frequency of the T allele was statistically significantly higher among the AD population than among the control group (p<0.05). The frequency of homozygotes without mutation (CC genotype) was 97.62%, while the frequency of heterozygotes for the mutation (CT genotype) was 2.38% among patients with AD, and the frequency of homozygotes without mutation (CC genotype) was 100% among healthy controls. Conclusion: Our study indicated a possible association of the heterozygous form of the R47H variant of TREM2 gene with the susceptibility for the deve-lopement of AD in Serbian population.

In neurodegenerative cerebellar ataxias, not only ataxia but also extra-cerebellar signs have a significant impact on patients’ health related to quality of life (HRQoL). The aim of this study was to evaluate the various aspects of HRQoL and predictors of QoL in patients with neurodegenerative cerebellar ataxias. We included a total of 107 patients with cerebellar degenerative ataxia. Patients filled out the validated Serbian version of the SF-36 used for the assessment of HRQoL. All patients were clinically evaluated using SARA, INAS, and neuropsychological tests to assess their global cognitive status and different psychiatric scales. The most frequent types of neurodegenerative cerebellar ataxias were autosomal dominant ataxias (38.3%) and sporadic ataxias (32.7%). Mean age at diagnosis was 35.3 ± 16.23 years, and disease duration was on average 12.1 ± 9.91 years. Mean total SF-36 score was 50.63 ± 20.50. Hierarchical regression analysis showed that in the case of the PHC score, the most significant predictors are the patient’s actual age, severity of ataxia, and ACE total score. For MHC, the Hamilton depression score was the most important predictor. Our study has shown that HRQoL measured by SF-36 in patients with neurodegenerative cerebellar disorders is strongly influenced by impaired mobility and depression.

Early-onset dementia (EOD) is conventionally considered to include patients with disease onset before 65 years of age, with Alzheimer’s disease (AD) being the most common form of EOD. Our aim was to investigate the clinical correlates of psychotropic therapy use in early onset AD (EOAD). This observational retrospective study included 135 consecutive EOAD patients who were diagnosed according to current criteria from April 1, 2012. until April 1, 2017. year at the Neurology Clinic, University Clinical Centre of Serbia. Neuropsychiatric symptoms were assessed using Neuropsychiatric inventory, Hamilton scale for depression and anxiety, and apathy scale. The frequency of psychotropic therapy use in our EOAD group was high with 85.18% patients receiving these drugs. Patients often received combinations of psychotropic drugs, 40% of patients received two psychotropic drugs (the most common was a combination of antidepressants and benzodiazepines). Clinical correlates of benzodiazepine administration in our group were agitation, irritability and anxiety. Antipsychotics use correlated with hallucinations, anxiety, irritability and sleep disorders. Psychotropic therapy was not associated with faster cognitive deterioration in EOAD patients, while more frequent functional deterioration correlated with the use of antipsychotics. The use of antipsychotics in patients with EOAD was not associated with serious side effects and reduced life expectancy. The frequency of psychotropic therapy use in our EOAD group was high. Psychotropic therapy was not associated with faster cognitive deterioration, serious side effects and reduced life expectancy in our EOAD patients.

Neuropsychiatric symptoms (NPS) occur frequently in patients with young onset Alzheimer’s Disease (YOAD). However, studies on psychotropic drug use (PDU) mainly focus on elderly patients with dementia. It is important to know the prevalence of PDU in patients with YOAD in order to reduce excess use of these medications in this group. Our study aim is to investigate the frequency of PDU among patients with YOAD. This is a retrospective study on 135 patientsfrom Memory Centre of Neurology Clinic, Clinical Centre of Serbia, with clinical diagnosis of YOAD. We included outpatients that had first visit to our clinic from 01.04.2012. to 01.04.2017. The data on psychotropic drug use werecollected from medical records. Statistical analyses were done using SPSS20. Mean age of our patients at inclusion was 60.07±5.27 and mean disease duration was 3.42±1.53. 85.18% patients received PT drugs. Antidepressants were prescribed most frequently, in 63.7% of patients, while antipsychotics were used by 45.93% of patients, and benzodiazepines by 61.5%. The earliest prescribed PTs were antidepressants, 3.66 years from the first symptoms and 1.45 years after diagnosis and antidepressants were used the longest in our group, 3.15 years. The frequency pf PDU in our cohort is high and comes close to PDU in patients in nursing homes in other European countries. The reason might be the high frequency of NPS in YOAD but also prescribing practice in the absence of systematic non pharmacological measures and that is something we have to take notice of.

BACKGROUND:The hypothesis that the effectiveness of deep brain stimulation (DBS) in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of stimulation and other brain regions is growing.OBJECTIVE:To investigate how the subthalamic nucleus (STN), the most frequently used DBS target for PD, is functionally linked to other brain regions in PD patients according to DBS eligibility.METHODS:Clinical data and resting-state functional MRI were acquired from 60 PD patients and 60 age- and sex-matched healthy subjects within an ongoing longitudinal project. PD patients were divided into 19 patients eligible for DBS and 41 non-candidates. Bilateral STN were selected as regions of interest and a seed-based functional MRI connectivity analysis was performed.RESULTS:A decreased functional connectivity between STN and sensorimotor cortex in both PD patient groups compared to controls was found. Whereas an increased functional connectivity between STN and thalamus was found in PD patient groups relative to controls. Candidates for DBS showed a decreased functional connectivity between bilateral STN and bilateral sensorimotor areas relative to non-candidates. In patients eligible for DBS, a weaker STN functional connectivity with left supramarginal and angular gyri was related with a more severe rigidity and bradykinesia whereas a higher connectivity between STN and cerebellum/pons was related to poorer tremor score.CONCLUSION:Our results suggest that functional connectivity of STN varies among PD patients eligible or not for DBS. Future studies would confirm whether DBS modulates and restores functional connectivity between STN and sensorimotor areas in treated patients.

Importance Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches.Objective To assess the incidence of FTLD across Europe.Design, Setting, and Participants The Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021.Main Outcomes and Measures Random-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity.Results Based on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057.Conclusions and Relevance The findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.

Specific feature of young onset Alzheimer’s disease (YOAD) patients is that their diagnosis and therefore their treatment is usually delayed. Firstly, they present atypically, secondly, they have a higher cognitive reserve and symptoms are later recognized and finally at that age, the family, and the patients themselves, do not think about the possibility of dementia, which prolongs the time period to seeking medical help (on average 2-3 years). To examine the association of survival in YOAD with time elapsed from the onset of symptoms to the initiation of pharmacotherapy. This is a retrospective study on 135 patients from Memory Center of Neurology Clinic, Clinical Center of Serbia, with clinical diagnosis of YOAD. We included outpatients that had first visit to our clinic from 01.04.2012. do 01.04.2017. The association of survival with time elapsed from onset of symptoms to initiation of therapy was examined by Kaplan Meier survival analysis with log rank test. From 2012, when the registry was created, till 2019, 89 out of 135 included patients died. Kaplan Meier survival analysis showed that patients with lower MMSE score (from 15 points and below) and who could not dress themselves or perform personal hygiene at the time of inclusion in our registry have a shorter expected survival than those who had MMSE 16 and above (p = 0.019) and who functioned independently in terms of these activities of daily living (p = 0.041 for dressing and p = 0.018 for performing personal hygiene). Patients in whom the introduction of therapy was delayed 3 or less years survived for a year longer than patients in whom therapy was introduced 4 or more years after the onset of dementia symptoms (p = 0.004). Our study clearly showed that certain clinical parameters (degree of cognitive and functional damage at the time of therapy introduction), but also delay in introducing therapy from symptoms onset determine the length of survival in YOAD.