2,471 research outputs found
Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages
OBJECTIVE
Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+).
METHODS
Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale.
RESULTS
In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN.
CONCLUSIONS
This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages
ANALISIS FAKTOR-FAKTOR YANG MEMPENGARUHI PRODUKSI IKAN BANDENG DI KOTA BANDA ACEH
ABSTRAKPenelitian ini bertujuan untuk mengetahui faktor-faktor yang mempengaruhi produksi ikan bandeng di Kota Banda Aceh. Penelitian ini dilakukan menggunakan metode survey dan pengambilan sampelnya dengan teknik sampel acak sederhana Simple Random Sampling.Lokasi penelitian dilakukan di Kota Banda Aceh, yaitu Kecamatan Syiah Kuala, Meuraxa, Kuta Alam, dan Kuta Raja. Waktu Penelitian dilaksanakan pada bulan Oktober 2013 sampai dengan Juli 2014. Model yang digunakan dalam penelitian ini adalah menggunakan model analisis kuantitatif untuk mengetahui Faktor-faktor yang mempengaruhi produksi ikan bandeng di Kota Banda Aceh yaitu tenaga kerja, luas tambak, jumlah nener, dan penggunaan pupuk..Untuk menguji hubungan antara variabel faktor-faktor yang mempengaruhi produksi ikan bandeng di Kota Banda Aceh, digunakan uji statistik dengan menggunakan uji T, F, dan R2.Hasil penelitian ini dapat disimpulkan bahwa secara serempak faktor , tenaga kerja, luas tambak, jumlah nener, dan jumlah pupuk berpengaruh nyata terhadap produksi ikan bandeng di Kota Banda Aceh. Secara parsial faktor jumlah nener berpengaruh nyata terhadap produksi ikan bandeng di Kota Banda Aceh. Sedangkan faktor tenaga kerja, luas tambak dan jumlah pupuk tidak berpengaruh nyata terhadap produksi ikan bandeng di Kota Banda Aceh.Kata Kunci: Ikan bandeng, analisis produksiABSTRACTThis research aims to determine the factors that affect fish production in the city of Banda Aceh. This research was conducted using a survey method and sampling with simple random sampling techniques.Location of the research conducted in the city of Banda Aceh , the District Syiah KuaLa, Meuraxa, Kuta Alam, and Kuta Raja. Time research conducted in October 2013 to July 2014 model used in this research was to use quantitative analysis model to determine the factors that affect milkfish production in Banda Aceh, namely labor, large farms, the amount of milkfish, and use of fertilizers.For Examine the relationship between the variable factors that affect milkfish production in Banda Aceh, used statistical tests using T test, F, and R2.The results of this research it can be concluded that the factors simultaneously, labor, large ponds, milkfish amount, and the amount of fertilizer significantly affect milkfish production in the city of Banda Aceh. Partially factors significantly affect the amount of milkfish fry production of milkfish in Banda Aceh. While the labor factor, vast farms and the amount of fertilizer had no significant effect on the production of milkfish in Banda Aceh .Keywords: Milkfish, production analysisBanda Ace
CSF Alzheimer's disease-like pattern in Corticobasal Syndrome: evidence for a distinct disorder.
Classification accuracy of blood-based and neurophysiological markers in the differential diagnosis of Alzheimerās disease and frontotemporal lobar degeneration
Background: In the last decade, non-invasive blood-based and neurophysiological biomarkers have shown great potential for the discrimination of several neurodegenerative disorders. However, in the clinical workup of patients with cognitive impairment, it will be highly unlikely that any biomarker will achieve the highest potential predictive accuracy on its own, owing to the multifactorial nature of Alzheimerās disease (AD) and frontotemporal lobar degeneration (FTLD). Methods: In this retrospective study, performed on 202 participants, we analysed plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau phosphorylated at amino acid 181 (p-Tau181) concentrations, as well as amyloid Ī²42 to 40 ratio (AĪ²1ā42/1ā40) ratio, using the ultrasensitive single-molecule array (Simoa) technique, and neurophysiological measures obtained by transcranial magnetic stimulation (TMS), including short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), long-interval intracortical inhibition (LICI), and short-latency afferent inhibition (SAI). We assessed the diagnostic accuracy of combinations of both plasma and neurophysiological biomarkers in the differential diagnosis between healthy ageing, AD, and FTLD. Results: We observed significant differences in plasma NfL, GFAP, and p-Tau181 levels between the groups, but not for the AĪ²1ā42/AĪ²1ā40 ratio. For the evaluation of diagnostic accuracy, we adopted a two-step process which reflects the clinical judgement on clinical grounds. In the first step, the best single biomarker to classify ācasesā vs ācontrolsā was NfL (AUC 0.94, p < 0.001), whilst in the second step, the best single biomarker to classify AD vs FTLD was SAI (AUC 0.96, p < 0.001). The combination of multiple biomarkers significantly increased diagnostic accuracy. The best model for classifying ācasesā vs ācontrolsā included the predictors p-Tau181, GFAP, NfL, SICI, ICF, and SAI, resulting in an AUC of 0.99 (p < 0.001). For the second step, classifying AD from FTD, the best model included the combination of AĪ²1ā42/AĪ²1ā40 ratio, p-Tau181, SICI, ICF, and SAI, resulting in an AUC of 0.98 (p < 0.001). Conclusions: The combined assessment of plasma and neurophysiological measures may greatly improve the differential diagnosis of AD and FTLD
Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias
Heterozygous mutations in the granulin (GRN) gene may result in haploinsufficiency of progranulin (PGRN), which might lead to frontotemporal dementia (FTD). In this study, we aimed to perform analytical and clinical validation of a commercial progranulin kit for clinical use. Analytical validation parameters including assay precision, selectivity, measurement range, dilution linearity, interferences and sample stability were tested according to previously described procedures. For clinical validation, PGRN levels were measured in plasma from 32 cognitively healthy individuals, 52 confirmed GRN mutation carriers, 25 C9orf72 mutation carriers and 216 patients with different neurodegenerative diseases of which 70 were confirmed as non-mutation carriers. Among the analytical validation parameters, assay precision and repeatability were very stable (coefficients of variation <7 %). Spike recovery was 96 %, the measurement range was 6.25-400 Ī¼g/L and dilution linearity ranged from 1:50-1:200. Hemolysis did not interfere with progranulin levels, and these were resistant to freeze/thaw cycles and storage at different temperatures. For the clinical validation, the assay was capable of distinguishing GRN mutation carriers from controls and non-GRN mutation carriers with very good sensitivity and specificity at a cut-off of 57 Ī¼g/L (97 %, 100 %, respectively). In this study, we demonstrate robust analytical and diagnostic performance of this commercial progranulin kit for implementation in clinical laboratory practice. This easy-to-use test allows identification of potential GRN mutation carriers, which may guide further evaluation of the patient. This assay might also be used to evaluate the effect of novel PGRN-targeting drugs and therapies
Prodromal frontotemporal dementia: clinical features and predictors of progression
Background: The prodromal phase of frontotemporal dementia (FTD) is still not well characterized, and conversion rates to dementia and predictors of progression at 1-year follow-up are currently unknown. // Methods: In this retrospective study, disease severity was assessed using the global CDR plus NACC FTLD. Prodromal FTD was defined to reflect mild cognitive or behavioural impairment with relatively preserved functional independence (global CDR plus NACC = 0.5) as well as mild, moderate and severe dementia (classified as global CDR plus NACC = 1, 2, 3, respectively). Disease progression at 1-year follow-up and serum NfL measurements were acquired in a subgroup of patients. // Results: Of 563 participants, 138 were classified as prodromal FTD, 130 as mild, 175 as moderate and 120 as severe FTD. In the prodromal and mild phases, we observed an early increase in serum NfL levels followed by behavioural disturbances and deficits in executive functions. Negative symptoms, such as apathy, inflexibility and loss of insight, predominated in the prodromal phase. Serum NfL levels were significantly increased in the prodromal phase compared with healthy controls (average difference 14.5, 95% CI 2.9 to 26.1 pg/mL), but lower than in patients with mild FTD (average difference -15.5, 95% CI -28.4 to -2.7 pg/mL). At 1-year follow-up, 51.2% of patients in the prodromal phase had converted to dementia. Serum NfL measurements at baseline were the strongest predictors of disease progression at 1-year follow-up (OR 1.07, 95% CI 1.03 to 1.11, p < 0.001). // Conclusions: Prodromal FTD is a mutable stage with high rate of progression to fully symptomatic disease at 1-year follow-up. High serum NfL levels may support prodromal FTD diagnosis and represent a helpful marker to assess disease progression
Transcranial direct current stimulation enhances theory of mind in Parkinson's disease patients with mild cognitive impairment: A randomized, double-blind, sham-controlled study
Mutation within TARDBP leads to Frontotemporal Dementia without motor neuron disease.
2009 AUG 4. [EPUB AHEAD OF PRINT
Comprehensive Evaluation of Plasma 7-Ketocholesterol and Cholestan-3Ī²,5Ī±,6Ī²-Triol in an Italian Cohort of Patients Affected by Niemann-Pick Disease due to NPC1 and SMPD1 Mutations
: Niemann-Pick C disease (NPCD) is a rare autosomal recessive neurovisceral disorder with a heterogeneous clinical presentation. Cholestan-3Ī²,5Ī±,6Ī²-triol and 7-ketocholesterol have been proposed as biomarkers for the screening of NPCD. In this work, we assessed oxysterols levels in a cohort of Italian patients affected by NPCD and analyzed the obtained results in the context of the clinical, biochemical and molecular data. In addition, a group of patients affected by Niemann-Pick B disease (NPBD) were also analyzed. NPC patients presented levels of both oxysterols way above the cut off value, except for 5 siblings presenting the variant biochemical phenotype who displayed levels of 3Ī²,5Ī±,6Ī²-triol below or just above the cut-off value; 2 of them presented also normal levels of 7-KC. Both oxysterols were extremely high in a patient presenting the neonatal systemic lethal phenotype. All NPB patients showed increased oxysterols levels. In conclusion, the reported LC-MS/MS assay provides a robust non-invasive screening tool for NPCD. However, false negative results can be obtained in patients expressing the variant biochemical phenotype. These data strengthen the concept that the results should always be interpreted in the context of the patients' clinical picture and filipin staining and/or genetic studies might still be undertaken in patients with normal levels of oxysterols if symptoms are highly suggestive of NPCD. Both oxysterols are significantly elevated in NPB patients; thus a differential diagnosis should always be performed in patients presenting isolated hepatosplenomegaly, a common clinical sign of both NPCD and NPBD
A Genome-Wide Screening and SNPs-to-Genes Approach to Identify Novel Genetic Risk Factors Associated with Frontotemporal Dementia
Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimerās disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel SNPs-to-genes approach and functional annotation analysis. We identified two novel potential loci for FTD. Suggestive SNPs reached p-values ~10-7 and OR > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation, and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-GWAS. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis
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