Cost-effectiveness of Alzheimer's disease CSF biomarkers and amyloid-PET in early-onset cognitive impairment diagnosis

This study aimed at determining the cost-effectiveness of amyloid-positron emission tomography (PET) compared to Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid-?42, total-Tau and phosphorylated-Tau) for the diagnosis of AD in patients with early-onset cognitive impairment. A decision tree model using a national health care perspective was developed to compare the costs and effectiveness associated with Amyloid-PET and AD CSF biomarkers. Available evidence from the literature and primary data from Hospital Clínic de Barcelona were used to inform the model and calculate the efficiency of these diagnostic alternatives. Medical visits and diagnostic procedures were considered and reported in €2020. We calculated the incremental cost-effectiveness ratio to measure the cost per % of correct diagnoses detected and we perform one-way deterministic and probabilistic sensitivity analyses to assess the uncertainty of these results. Compared with AD CSF biomarkers, Amyloid-PET resulted in 7.40% more correctly diagnosed cases of AD, with an incremental total mean cost of €146,854.80 per 100 cases. We found a 50% of probability that Amyloid-PET was cost-effective for a willingness to pay (WTP) of €19,840.39 per correct case detected. Using a WTP of €75,000, the probability that it is cost-effective reached a maximum of 76.9%, thus leading to a conclusion that Amyloid-PET is not a cost-effective technique compared to AD CSF biomarkers, unless the funder is willing to pay a minimum of €19,840.39 to detect one more correct case. Furthermore, obtaining CSF provides simultaneous information on amyloid ? and tau biomarkers and allows other biomarkers to be analyzed at a relatively low cost.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany

First report of Berkeleyomyces basicola (synonymous: Thielaviopsis basicola) on roots of sweet potato (Ipomoea batatas (L.) Lam) in Argentina

Symptomatic sweet potato cv Arapey INIA samples were collected from a commercial production field in Colonia Molina, Guaymallén department, Mendoza province, Argentina. They showed dark rounded lesions, sometimes coalescing with white granular mycelium. Fungus was obtained from symptomatic sweet potatoes, which represented the generalized infection that affected the crop. They were seeded in PDA with streptomycin sulfate and incubated for seven days at 21°C, alternating white/black (UV400nm) light. Observations with an optical microscope revealed the presence of hyaline, not septated, cylindrical endoconidia with rounded ends. They were 8-16 μm length and 4–6 μm width. Phialides were 43-46 μm length, rounded bases (7-9 μm width) and tapering to the neck´s tip (4-6 μm width). Brown chlamydospores (aleuriospores), 9-13 μm length and 8-12 μm width, in chains of 2-8 spores were observed. For molecular identification, total genomic DNA was extracted. ITS fragment of 565 pb was amplified using ITS5/ITS4 primers and sequenced. The sequence indicated 99% identity with Berkeleyomyces basicola (synonymous: Thielaviopsis basicola). This was deposited in GenBank as (KX580957) (CBS: C430.74, Gen Bank accession number AF275482.1). This is the first report of B. basicola in sweet potato in Argentina, a potential threat to storage root yields. Highlights: Sweet potato black root rot, new disease in Argentina. First report of Berkeleyomyces basicola  causing black root rot on sweet potato in Mendoza, Argentina.Symptomatic sweet potato cv Arapey INIA samples were collected from a commercial production field in Colonia Molina, Guaymallén department, Mendoza province, Argentina. They showed dark rounded lesions, sometimes coalescing with white granular mycelium. Fungus was obtained from symptomatic sweet potatoes, which represented the generalized infection that affected the crop. They were seeded in PDA with streptomycin sulfate and incubated for seven days at 21°C, alternating white/black (UV400nm) light. Observations with an optical microscope revealed the presence of hyaline, not septated, cylindrical endoconidia with rounded ends. They were 8-16 μm length and 4–6 μm width. Phialides were 43-46 μm length, rounded bases (7-9 μm width) and tapering to the neck´s tip (4-6 μm width). Brown chlamydospores (aleuriospores), 9-13 μm length and 8-12 μm width, in chains of 2-8 spores were observed. For molecular identification, total genomic DNA was extracted. ITS fragment of 565 pb was amplified using ITS5/ITS4 primers and sequenced. The sequence indicated 99% identity with Berkeleyomyces basicola (synonymous: Thielaviopsis basicola). This was deposited in GenBank as (KX580957) (CBS: C430.74, Gen Bank accession number AF275482.1). This is the first report of B. basicola in sweet potato in Argentina, a potential threat to storage root yields. Highlights: Sweet potato black root rot, new disease in Argentina. First report of Berkeleyomyces basicola  causing black root rot on sweet potato in Mendoza, Argentina

Design and validation of the 1-week memory battery for assessing episodic memory and accelerated long-term forgetting in cognitively unimpaired subjects

Subtle decline in memory is thought to arise in the preclinical phase of Alzheimer's disease (AD). However, detecting these initial cognitive difficulties cross-sectionally has been challenging, and the exact nature of the decline is still debated. Accelerated long-term forgetting (ALF) has been recently suggested as one of the earliest and most sensitive indicators of memory dysfunction in subjects at risk of developing AD. The objective of this study was to design and validate the 1-week memory battery (1WMB) for assessing episodic memory and ALF in cognitively unimpaired individuals.The 1WMB is unique in that it assesses multimodal memory and measures recall at both short delay (20 min) and at long term (1 week). Forty-five cognitively unimpaired subjects were assessed with 1WMB and standardized neuropsychological tests. Subjective cognitive decline (SCD), levels of anxiety and depression, and cognitive reserve were also measured.The tests of 1WMB showed a high internal consistency, and concurrent validity was observed with standard tests of episodic memory and executive functions. The analysis revealed a greater loss of information at 1 week compared to short-term forgetting (20 min). Performance in the 1WMB was affected by age and educational level, but was not associated with levels of anxiety and depression. Unlike standard tests, performance in the 1WMB correlated with measures of SCD.Our findings indicate that the 1WMB has good psychometric properties, and future studies are needed to explore its potential usefulness to assess cognitively unimpaired subjects at increased risk of developing AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Brillouin scattering study on the single-crystal elastic properties of natrolite and analcime zeolites

Copyright © 2005 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Journal of Applied Physics 98 (2005) and may be found at http://link.aip.org/link/?jap/98/053508The Brillouin light-scattering technique was used to investigate the single-crystal elastic properties of two aluminosilicate zeolites, natrolite (NAT) and analcime (ANA), at ambient conditions. An inversion of the acoustic velocity data results in the full set of elastic stiffness moduli (Cij's) for both materials. From the single-crystal moduli the aggregate adiabatic bulk moduli (Ks), shear moduli (G), and Poisson's ratios (v) were found to be Ks=48.5(1.0) GPa, G=31.6(1.0) GPa, and v =0.232(5) for NAT, and Ks=59.8(1.2) GPa, G=32.1(1.0) GPa, and v=0.272(5) for ANA (Voigt-Reuss-Hill averages). The bulk and shear moduli of both zeolites are relatively low compared with those of densely packed aluminosilicates, reflecting an open framework structure of (Al,SiO4) tetrahedra which is easily deformed by bending the Si–O–Al angles. As expected for a less dense crystal, NAT is softer and more compressible than ANA. An evaluation of the directional Young's moduli shows that the compressibility of NAT is nearly uniform along the [100] and [010] axes, while [001] is stiffer, in agreement with previous compression studies. We do not find experimental evidence of negative Poisson's ratios for NAT zeolites as predicted by recent theoretical calculations

Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies

The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10–15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD

Plasma levels of soluble TREM2 and neurofilament light chain in TREM2 rare variant carriers

Background: Results from recent clinical studies suggest that cerebrospinal fluid (CSF) biomarkers that are indicative of Alzheimer’s disease (AD) can be replicated in blood, e.g. amyloid-beta peptides (Aβ42 and Aβ40) and neurofilament light chain (NFL). Such data proposes that blood is a rich source of potential biomarkers reflecting central nervous system pathophysiology and should be fully explored for biomarkers that show promise in CSF. Recently, soluble fragments of the triggering receptor expressed on myeloid cells 2 (sTREM2) protein in CSF have been reported to be increased in prodromal AD and also in individuals with TREM2 rare genetic variants that increase the likelihood of developing dementia. / Methods: In this study, we measured the levels of plasma sTREM2 and plasma NFL using the MesoScale Discovery and single molecule array platforms, respectively, in 48 confirmed TREM2 rare variant carriers and 49 non-carriers. / Results: Our results indicate that there are no changes in plasma sTREM2 and NFL concentrations between TREM2 rare variant carriers and non-carriers. Furthermore, plasma sTREM2 is not different between healthy controls, mild cognitive impairment (MCI) or AD. / Conclusion: Concentrations of plasma sTREM2 do not mimic the recent changes found in CSF sTREM2

Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [3H]Glutamate Binding to Rat Synaptic Membranes

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [3H]Glutamate. Aqueous valerian extract increased [3H]Glutamate binding from 1 × 10−7 to 1 × 10−3 mg/mL. In the presence of (2S,1′S,2′S)-2-(Carboxycyclopropyl)glycine (LCCG-I) and (2S,2′R,3′R)-2-(2′,3′-Dicarboxycyclopropyl)glycine (DCG-IV), Group II mGluR agents, valerian extract markedly decreased [3H]Glutamate binding, while (2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [3H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [3H]Glutamate binding after 1.6 × 10−2 mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant

Misfolded α-Synuclein in Autosomal Dominant Alzheimer's Disease.

We analyzed Lewy body (LB) pathology in 18 autosomal dominant Alzheimer's disease (ADAD) brains via immunohistochemistry. Real-time quaking induced conversion was used to detect misfolded α-synuclein (α-syn) in 18 living ADAD cerebrospinal fluid (CSF) samples. Concomitant LB pathology was present in 44% ADAD brains. Only 6% CSF samples were positive for misfolded α-syn. In an additional AD sample, all patients with confirmed LB presented misfolded α-syn in postmortem CSF regardless of the LB staging. In conclusion, misfolded α-syn in CSF was scarce in symptomatic living ADAD individuals, in contrast to postmortem brain tissue. These results suggest late appearance of LB pathology in ADAD

Cortical thickness modeling and variability in Alzheimer's disease and frontotemporal dementia

Alzheimer's disease (AD) and frontotemporal dementia (FTD) show different patterns of cortical thickness (CTh) loss compared with healthy controls (HC), even though there is relevant heterogeneity between individuals suffering from each of these diseases. Thus, we developed CTh models to study individual variability in AD, FTD, and HC.We used the baseline CTh measures of 379 participants obtained from the structural MRI processed with FreeSurfer. A total of 169 AD patients (63 ± 9 years, 65 men), 88 FTD patients (64 ± 9 years, 43 men), and 122 HC (62 ± 10 years, 47 men) were studied. We fitted region-wise temporal models of CTh using Support Vector Regression. Then, we studied associations of individual deviations from the model with cerebrospinal fluid levels of neurofilament light chain (NfL) and 14-3-3 protein and Mini-Mental State Examination (MMSE). Furthermore, we used real longitudinal data from 144 participants to test model predictivity.We defined CTh spatiotemporal models for each group with a reliable fit. Individual deviation correlated with MMSE for AD and with NfL for FTD. AD patients with higher deviations from the trend presented higher MMSE values. In FTD, lower NfL levels were associated with higher deviations from the CTh prediction. For AD and HC, we could predict longitudinal visits with the presented model trained with baseline data. For FTD, the longitudinal visits had more variability.We highlight the value of CTh models for studying AD and FTD longitudinal changes and variability and their relationships with cognitive features and biomarkers.© 2023. The Author(s)