The Erlangen Score Algorithm in the diagnosis and prediction of the progression from subjective cognitive decline and mild cognitive impairment to Alzheimer-type dementia.

The evaluation of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) (ß-amyloid, t-tau, p-tau) can be used to estimate the risk of developing dementia in patients at the pre-clinical stages of AD, i.e. subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Erlangen Score Algorithm allows interpretation of CSF biomarker concentrations and is cut-off value independent. The aim of this study was to establish if this algorithm can be applied for routine diagnostic testing in clinical and preclinical subjects and has prognostic value. We analysed 217 patients from the memory clinic with the diagnosis of SCD (n = 31), MCI (n = 104), and AD (n = 82) with clinical follow-up amounting to 14.33 months (SD = 6.82). It was found that the highest Erlangen Score dominated in the AD group and was the rarest in the SCD group. In the group of patients with progression of symptoms during our period of observation, the AD pathology was confirmed in 93.75% of cases. Among the non-progressing subjects (n = 119) the algorithm indicated the risk of developing AD as possible in 40.34% and probable in 15.97% of cases. To conclude, the Erlangen Score Algorithm is a useful tool to determinate the risk of developing AD before the onset of dementia or to confirm the AD diagnosis. It is extremely valuable in preclinical stages of AD for planning purposes and early intervention as well as for future clinical trials.

TREM2 variants in neurodegenerative disorders in the Polish population. Homozygosity and compound heterozygosity in FTD patients.

Activation of the TREM2 receptor on microglia stimulates phagocytosis and decreases the microglial proinflammatory response. Mutations in exon 2 of the TREM2 gene have been reported to be associated with various neurodegenerative diseases characterized by chronic inflammation. The aim of our study was to evaluate exon 2 of TREM2 gene variants as a putative genetic risk factor for Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) in the Polish population. The results were interpreted using previously published data, especially highlighting differences in the prevalence of the variants among Caucasian subpopulations across different geographic regions. The DNA sequence of exon 2 of TREM2 was analyzed in 811 subjects (274 AD, 135 FTD, 194 ALS patients, and 208 neurologically healthy controls). Nine heterozygous variants were detected, including two novel ones: p.G29 = and c.41-2_3insA, found respectively in a control and an ALS patient. Additionally, we identified one homozygous and two compound heterozygous FTD patients. We confirm previous data that homozygous and compound heterozygous TREM2 mutations can be causative for FTD.

Fahr Syndrome - an Important Piece of a Puzzle in the Differential Diagnosis of Many Diseases.

Fahr syndrome is a rare neurodegenerative disorder characterized by symmetrical, bilateral calcifications in the basal ganglia, nucleus gyrus and cerebral cortex. The continuous advancement as well as widespread use of brain imaging have contributed to the increasing detection rates of such changes. Nevertheless, their etiology is understood only partially and the methods of causative treatment are limited. Due to various symptoms, Fahr syndrome may resemble diseases from the field of neurology, psychiatry, cardiology and even urology. This article provides an up-to-date review of the literature concerning Fahr syndrome in terms of clinical practice.

Association between Cerebrospinal Fluid Biomarkers for Alzheimer's Disease, APOE Genotypes and Auditory Verbal Learning Task in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

In the course of Alzheimer's disease (AD), early pathological changes in the brain start decades before any clinical manifestation. The concentration levels of AD cerebrospinal fluid (CSF) biomarkers, such as amyloid-ß1-42 (Aß1-42), total tau (T-tau), and phosphorylated tau (P-tau), may reflect a cerebral pathology facilitating an early diagnosis of the disease and predicting a cognitive deterioration. The aim of this study was to estimate the prevalence of AD CSF biomarkers in those individuals with a subjective cognitive decline (SCD), a mild cognitive impairment (MCI), and Alzheimer's dementia (AD-D), together with the relationships between the biomarkers, an APOE ɛ4 presence, and a verbal episodic memory performance. We included 252 patients from the memory clinic with a diagnosis of SCD (n = 85), MCI (n = 87), and AD-D (n = 80). A verbal episodic memory performance level was assessed and was based on a delayed recall trial from the 10-word list of an auditory verbal learning task (AVLT). We found that the patients with more severe cognitive impairments had significantly lower levels of Aß1-42 and higher levels of T-tau and P-tau. This pattern was also typical for the APOE ɛ4 carriers, who had lower levels of Aß1-42 than the noncarriers in the AD-D and MCI groups. The levels of T-tau and P-tau were significantly higher in the APOE ɛ4 carriers than in the noncarriers, but only in the MCI patients. The AVLT performance in the whole study samples was predicted by age, Aß1-42, and the T-tau CSF biomarkers, but not by the APOE genotyping.

Combined use of biochemical and volumetric biomarkers to assess the risk of conversion of mild cognitive impairment to Alzheimer's disease.

INTRODUCTION: The aim of our study was to evaluate the usefulness of several biomarkers in predicting the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD): ß-amyloid and tau proteins in cerebrospinal fluid and the volumetric evaluation of brain structures including the hippocampus in magnetic resonance imaging (MRI). MATERIAL AND METHODS: MRI of the brain with the volumetric assessment of hippocampus, entorhinal cortex, posterior cingulate gyrus, parahippocampal gyrus, superior, medial and inferior temporal gyri was performed in 40 patients diagnosed with mild cognitive impairment. Each patient had a lumbar puncture to evaluate ß-amyloid and tau protein (total and phosphorylated) levels in the cerebrospinal fluid. The observation period was 2 years. RESULTS: Amongst 40 patients with MCI, 9 (22.5%) converted to AD within 2 years of observation. Discriminant analysis was conducted and sensitivity for MCI conversion to AD on the basis of volumetric measurements was 88.9% and specificity 90.3%; on the basis of ß-amyloid and total tau, sensitivity was 77.8% and specificity 83.9%. The combined use of the results of volumetric measurements with the results of proteins in the cerebrospinal fluid did not increase the sensitivity (88.9%) but increased specificity to 96.8% and the percentage of correct classification to 95%.

Predicting the conversion of mild cognitive impairment to Alzheimer's disease based on the volumetric measurements of the selected brain structures in magnetic resonance imaging.

INTRODUCTION: Mild cognitive impairment (MCI) is defined as abnormal cognitive state, but does not meet the criteria for the diagnosis of dementia. According to the new guidelines Alzheimer's disease (AD) involves not only dementia's phase but also predementia phase which is asymptomatic and pathological process in the brain is already present. For this reason it is very important to determine the suitability of markers which should be positive before onset of the first symptoms. One of these biomarkers is a structural magnetic resonance imaging with hippocampal volumetric assessment. The aim of this study was to investigate the usefulness of structural brain magnetic resonance imaging with volumetric assessment of the hippocampus and entorhinal cortex, posterior cingulate gyrus, parahippocampal gyrus, temporal gyri: superior, medial and inferior, to predict the conversion of MCI to AD. MATERIAL AND METHODS: Magnetic resonance imaging of brain was performed at the baseline visit in 101 patients diagnosed with MCI. Clinic follow-ups were scheduled after 6.12 and 24 months. RESULTS: Amongst 101 patients with MCI, 17 (16.8%) converted into AD within two years of observation. All measured volumes were lower in converters than non-converters. Discriminant analysis was conducted and sensitivity for MCI conversion to AD was 64.7%, specificity 96.4%. 91% of patients were correctly classified (converter or non-converter). CONCLUSIONS: Volumetric measurements may help clinicians to predict MCI conversion to AD but due to low sensitivity it cannot be use separately. The study group requires further observation.