Frontotemporal dementia is a progressive neurodegenerative disorder with high clinical, genetic, and pathomorphological diversity It is the third most common cause of dementia in all ages and the most common cause of early onset dementia (below 65). Despite its multifactorial nature, up to 40% of patients have a family history where the autosomal dominant inheritance type is seen in a quarter of cases. In this review, we describe key genes whose mutations can result in the development of frontotemporal dementia, the possible pathogenic mechanisms of the degenerative process, and provide information on the clinical features of the disease for different genetic variants. Special emphasis is placed on the frontotemporal dementia phenotype that is associated with amyotrophic lateral sclerosis.

Frontotemporal dementia is a progressive neurodegenerative disorder with high clinical, genetic, and pathomorphological diversity It is the third most comm

Background. Spinal muscular atrophy (SMA) associated with chromosome 5q is an autosomal recessive neuromuscular disease caused by a mutation in the SMN1 gene. Adult forms of SMA are relatively rarer and associated with significant diagnostic difficulties and pronounced delay in diagnosis. The available pathogenetic therapy for SMA has the greatest effect with an earlier start of treatment, so timely diagnosis of the disease significantly improves the overall prognosis.Aim. To evaluate the features of diagnosis of the adult SMA and summarize the first experience of such diagnosis in Russian patients.Materials and methods. We analyzed the archived medical records of 50 adult patients with SMA consulted at the Research Center of Neurology (Moscow).Results. The data of patients with SMA type 2 (n = 26), SMA type 3 (n = 21), SMA type 4 (n = 3) were analyzed. The delay time for diagnosis in SMA type 2 is 35 (0–270) months, with SMA types 3 and 4 – 108 (0–408) months. The diagnosis of SMA was the first diagnosis in SMA type 2 in 69 % of cases, in SMA types 3 and 4 in 29 % of cases. The most common first diagnosis in patients with SMA is myopathy, accounting for 52 % of all misdiagnosed cases. A small percentage of the use of needle electromyography in the diagnostic process was noted (1/3 of cases); in cases of its use, this did not accelerate the correct diagnosis. Creatine phosphokinase activity is often elevated in patients with SMA types 3 and 4 compared with SMA type 2 (p 0.05). Conclusions. To reduce the delay in the correct diagnosis of SMA and earlier initiation of pathogenetic therapy, it is necessary to increase the awareness of specialists about the features of diagnosis the disease and focus on alternative erroneous diagnoses, among which adult patients with SMA may “hide”. The key to confirming the diagnosis is DNA testing.

Naming decline is one of the most common symptoms of primary progressive aphasia (PPA). Most studies on anomia in PPA are performed without taking into account PPA variants, especially for action naming. Only limited data are available for the neuroanatomical basis of anomia considering differences in the pathogenesis of PPAs. The aim of our study is to investigate the associations between anomia severity for both noun and verb naming and gray matter (GM) atrophy, as well as accompanying functional connectivity (FC) changes in three PPA variants. A total of 17 patients with non-fluent (nfvPPA), 11 with semantic (svPPA), and 9 with logopenic (lvPPA) PPA variants were included in the study and underwent cognitive/naming assessments and brain MRIs. Voxel-based morphometry was performed to evaluate GM volume. A resting-state functional MRI was applied to investigate FC changes in the identified GM areas. The study shows that different brain regions are involved in naming decline in each PPA variant with a predominantly temporal lobe involvement in svPPA, parietal lobe involvement in lvPPA, and frontal lobe involvement in nfvPPA. Separate data for object and action naming in PPA variants are provided. The obtained results mainly correspond to the current understanding of language processing and indicate that the evaluation of language impairments is preferable for each PPA variant separately. A further analysis of larger cohorts of patients is necessary to confirm these preliminary results.

Objective. To evaluate the frequency of Alzheimer’s disease (AD) confirmed by cerebrospinal fluid (CSF) biomarkers in a cohort of patients with classical (amnesic) and atypical phenotypes of this disease. Material and methods. The study included 63 patients (24 men and 39 women; median age 65 years [60; 71]). All patients were divided into 3 groups according to the phenotype: a classic amnesic phenotype (n=32), frequent non-amnesic phenotypes (n=21) and rare non-amnesic phenotypes (n=10). All patients underwent lumbar puncture followed by the CSF biomarkers evaluation (beta-amyloid 1—42 (Aβ1—42) and phosphorylated tau protein 181 (p-tau181)) to confirm the AD pathology. The clinical characteristics of each subgroup were studied. Results. A decreased level of CSF Aβ1—42 in combination with an increased level of p-tau181 was found in 36 patients (57.1%). A change in at least one biomarker was detected in 54 patients (85.7%). The highest frequency of the Alzheimer’s type pathology was found in the group with predominant amnestic phenotype (87.5%), as well as in the subgroups with logopenic variant of primary progressive aphasia (lvPPA) (100%) and with posterior cortical atrophy (PCA) (100%). In the group with rare phenotypes, the frequency of AD CSF changes characteristic of AD was 50% for patients with predominant behavioral disorders and 66.7% for corticobasal syndrome. Conclusion. The high frequency of AD CSF biomarkers in both the classical (amnesic) and atypical phenotypes is shown. This indicates the need to expand the use of AD CSF biomarkers for a more reliable assessment of the prevalence of AD In Russia.