Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients(648 views) Ciarmiello A, Tartaglione A, Giovannini E, Riondato M, Giovacchini G, Ferrando O, De Biasi M, Passera C, Carabelli E, Mannironi A, Foppiano F, Alfano B, Mansi L
Nuclear Medicine Department, S. Andrea Hospital, 19124, La Spezia, Italy. andrea.ciarmiello@asl5.liguria.it.
Memory Laboratory CNS-ONLUS, 19124, La Spezia, Italy.
Medical Physics Department, S. Andrea Hospital, 19124, La Spezia, Italy.
Department of Neurology, S. Andrea Hospital, 19124, La Spezia, Italy.
Biostructure and Bioimaging Institute, National Research Council, 80145, Naples, Italy.
Interuniversitary Research Center for Sustainable Development (CIRPS), 00038, Rome, Italy.
References: Not available.
Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients
- PURPOSE: The extent of amyloid burden associated with cognitive impairment in amnestic mild cognitive impairment is unknown. The primary aim of the study was to determine the extent to which amyloid burden is associated to the cognitive impairment. The secondary objective was to test the relationship between amyloid accumulation and memory or cognitive impairment. MATERIALS AND METHODS: In this prospective study 66 participants with amnestic mild cognitive impairment underwent clinical, neuropsychological and PET amyloid imaging tests. Composite scores assessing memory and non-memory domains were used to identify two clinical classes of neuropsychological phenotypes expressing different degree of cognitive impairment. Detection of amyloid status and definition of optimal amyloid +/- cutoff for discrimination relied on unsupervised k-means clustering method. RESULTS: Threshold for identifying low and high amyloid retention groups was of SUVr = 1.3. Ass + participants showed poorer global cognitive and episodic memory performance than subjects with low amyloid deposition. Ass positivity significantly identified individuals with episodic memory impairment with a sensitivity and specificity of 80 and 79%, (chi2 = 21.48; P < 0.00001). Positive and negative predictive values were 82 and 76%, respectively. Amyloid deposition increased linearly as function of memory impairment with a rate of 0.13/ point of composite memory score (R = -44, P = 0.0003). CONCLUSION: The amyloid burden of SUVr = 1.3 allows early identification of subjects with episodic memory impairment which might predict progression from MCI to Alzheimer's disease. TRIAL REGISTRATION: EudraCT 2015-001184-39. - Alcohol consumption is one of the main risks to public health. Alcohol Use Disorders (AUDs) cause 80% of hepatotoxic deaths, and approximately 50% of cirrhosis is alcoholrelated. The acceptable daily intake (ADI) for ethanol is 2.6 g/day, deduced from morbidity and mortality rates due to liver fibrosis. The relative risk of cirrhosis increases significantly for doses above 60 g/day for men and 20 g/day for women over a period of around 10 years. Twenty to 40% of steatosis cases will evolve into steatohepatitis / steatofibrosis, and 8 to 20% will evolve directly into liver cirrhosis. About 20 to 40% of steatohepatitis cases will evolve into cirrhosis, and 4 to 5% into hepatocellular carcinoma. This cascade of events evolves in 5 to 40 years, with the temporal variability caused by the subjects' genetic patterns and associated risk / comorbidity factors. Steatohepatitis should be considered "the rate limiting step": usually, it can be resolved through abstinence, although for some patients, once this situation develops, it is not substantially modified by abstention and there is a risk of fibrotic evolution. Early detection of fibrosis, obtained by hepatic elastography, is a crucial step in patients with AUDs. Such strategy allows patients to be included in a detoxification program in order to achieve abstention. Drugs such as silybin, metadoxine, and adenosylmethionine can be used. Oher drugs, with promising antifibrotic effects, are currently under study. In this review, we discuss clinical and pathogenetic aspects of alcoholrelated liver fibrosis and present and future strategies to prevent cirrhosis. - Mesenchymal stem cells hold great promise for regenerative medicine as they can be easily isolated from different sources such as adipose tissue, bone marrow, and umbilical cord blood. Spontaneously arising pluripotent stem cells can be obtained in culture from murine spermatogonial stem cells (SSCs), while the pluripotency of the human counterpart remains a matter of debate. Recent gene expression profiling studies have demonstrated that embryonic stem cell- (ESC-) like cells obtained from the human testis are indeed closer to mesenchymal stem cells (MSCs) than to pluripotent stem cells. Here, we confirm that colonies derived from human testicular cultures, with our isolation protocol, are of mesenchymal origin and do not arise from spermatogonial stem cells (SSCs). The testis, thus, provides an important and accessible source of MSCs (tMSCs) that can be potentially used for nephrotoxicity testing in vitro. We further demonstrate, for the first time, that tMSCs are able to secrete microvesicles that could possibly be applied to the treatment of various chronic diseases, such as those affecting the kidney. - AIMS: Diabetes and cancer frequently coexist in the same subject, often having relevant effects on the management and prognosis of the oncologic patient. However, existing guidelines do not deal with many clinical issues in this setting appropriately. In evaluating the opinions of Diabetologists and Oncologists dealing with diabetes care in people with cancer, the Italian Association of Diabetologists (AMD) promoted a dedicated exploratory survey. METHODS: The survey was carried out through the web or handily delivered printed copies between October 2014 and April 2015, in Italy. It was composed of 27 questions intended to gather information on the characteristics of participants and to examine their clinical habits in this context, and participation was totally free and anonymous. RESULTS: A total of 252 physicians participated in the survey. Diabetologists accounted for 51.1% of respondents. According to survey results, in spite of the presence of diabetes (or diabetic complications) worsening the outcome of cancer treatments, the counseling or intervention of a Diabetologist was only required for less than two-thirds of hospitalized patients. For subjects with a life expectancy of months, 80% of specialists considered a glycemic target of 120-250mg/dL optimal whereas Oncologists were more likely to consider a range of 180-360mg/dL for patients with a shorter life expectancy. Furthermore, 1 participant out of 3 indicated 1-4 measurements/day as the most appropriate frequency for blood glucose monitoring including in the palliative setting. Insulin was the therapy of choice for the majority of respondents albeit with different routes of administration. CONCLUSIONS: This survey provides interesting preliminary data that could help facilitate and optimize the management of patients with cancer and diabetes, promoting the delivery of an organic answer to fragmented assistance, to potentially inappropriate behaviors, and to a tailored therapy in a context of particular clinical fragility. - PURPOSE: Cerebral palsy (CP) is a disorder characterized by an increased muscle stiffness that can be contingent on both neurological and biomechanical factors. The neurological aspects are related to hyper-excitability of the stretch reflex, while the biomechanical factors are related to modifications in muscle structure. We used smart-shear wave elastography (S-SWE) to analyze muscle properties and to compare shear wave speed in soleus muscles of patients affected by CP and typically developing children. METHODS: We enrolled 21 children (15 males and 6 females; age range 3-16) with spastic hemiplegia CP and 21 healthy children (11 males and 10 females; age range 3-14). Measurements of soleus S-SWE were performed using a Samsung RS80A ultrasound scanner with Prestige equipment (Samsung Medison Co. Ltd., Seoul, Korea), with a convex array transducer (CA1-7; Samsung Medison Co. Ltd., Seoul, Korea). For each CP child clinical assessment included Modified Ashworth Scale (MAS) score. RESULTS: Children with CP showed greater S-SWE values than the healthy ones (p < 0.001). Our data suggest a significant correlation between the S-SWE values and the MAS scores (Spearman correlation coefficient 0.74; p < 0.001 at Kruskal-Wallis test) in children with CP. CONCLUSIONS: Measuring muscle properties with SWE, a non-invasive and real-time technique, may integrate the physical exam. SWE may be a reliable clinical tool for diagnosis and longitudinal monitoring of muscle stiffness, as well as particularly suitable for grading and for assessing the response to treatments. - Persistent urogenital sinus (PUGS) is a congenital pathological condition characterized by an abnormal communication between the urethra and vagina, which has an estimated incidence of 0.6/10,000 female births. It could be the only known malformation or part of a syndrome. PUGS is commonly shown by a pelvic mass, related to a distended bladder, hydrometrocolpos which is due to an obstruction leading to the dilation of the vagina and uterus (i.e., imperforate hymen, transverse vaginal septum or atresia, and PUGS) or both. We present a case of female patient with classical congenital adrenal hyperplasia, diagnosed on the 7th day of life, with ambiguous genitalia, untreated surgically only with hormone therapy by parental decision. The patient, at the age of 5 years and 5 months, came to our observation for a pelvic ultrasound, which revealed retrovesical neoformation with anechoic content and regular walls. We performed the ultrasound examination that showed the dilation of the cervix and the vaginal canal with anechoic finely corpuscolated content in the declining portion, compatible with hydrometrocolpos from probable persistence of the urogenital sinus. The voiding cystourethrography (VCUG) confirmed the ultrasound diagnosis, with evidence of urogenital sinus. In conclusion, ultrasound is the first diagnostic tool, but need to be completed by other technical procedures, which VCUG or magnetic resonance imaging to observe the site of fusion of the urinary and genital tract. - OBJECTIVE: To correlate clinical and pathological characteristics at diagnosis with patient long-term outcomes and to evaluate ongoing risk stratifications in a large series of paediatric differentiated thyroid cancers (DTC). STUDY DESIGN: Retrospective analysis of clinical and pathological prognostic factors of 124 paediatric patients with DTC (age at diagnosis <19 years) followed up for 10.4 +/- 8.4 years. Patients with a follow-up >3 years (n = 104) were re-classified 18 months after surgery on the basis of their response to therapy (ongoing risk stratification). RESULTS: Most patients had a papillary histotype (96.0%), were older than 15 years (75.0%) and were diagnosed because of clinical local symptoms (63.7%). Persistent/recurrent disease was present in 31.5% of cases during follow-up, but at the last evaluation, only 12.9% had biochemical or structural disease. The presence of metastases in the lymph nodes of the lateral compartment (OR 3.2, 95% CI, 1.28-7.16, P = 0.01) was the only independent factor associated with recurrent/persistent disease during follow-up. At the last evaluation, biochemical/structural disease was associated with node metastases (N1a, N1b) by univariate but not multivariate analysis. Ongoing risk stratification compared to the initial risk classification method better identified patients with a lower probability of persistent/recurrent disease (NPV = 100%). CONCLUSIONS: In spite of the aggressive presentations at diagnosis, paediatric patients with DTC show an excellent response to treatment and often a favourable outcome. N1b status should be considered a strong predictor of persistent/recurrent disease which, as in adults, is better predicted by ongoing risk stratification. - Introduction: There are several reported cases of patients developing motor and cognitive neurological impairment under treatment with valproic acid (VPA). We describe a woman who developed a subacute encephalopathy after VPA intake, harboring a mitochondrial DNA variant, previously described as causing VPA sensitivity in one pediatric patient. Material and Methods: A 65-year old woman developed a progressive, severe neurological deterioration after a 3 month treatment with valproate sodium, 800 mg daily. Magnetic resonance spectroscopy (MRS), muscle histochemical analysis and assay of mitochondrial enzymatic activities, and mitochondrial DNA sequencing were performed. Results: Neurological examination showed drowsiness, vertical gaze palsy, inability to either stand or walk, diffuse weakness, increased tendon reflexes. Blood lactate was increased, EEG showed diffuse theta and delta activity, MRI subcortical atrophy and leukoencephalopathy, MRS marked reduction of the NAA spectrum, with a small signal compatible with presence of lactate. Muscle biopsy evidenced presence of ragged red fibers (20%) and reduced COX reactivity. Assay of the muscle enzymatic activities showed multiple deficiencies of the electron transport chain and reduced ATP production. The mt.8393C>T variant in the MT-ATP8 gene was found in homoplasmy. The patient considerably improved after valproate withdrawal. Conclusion: The variant we found has been reported both as a polymorphism and, in a single patient, as related to the valproate-induced encephalopathy. The present case is the first bearing this mutation in homoplasmy. In case of neurological symptoms after starting VPA therapy, once hyperammonemia and liver failure have been ruled out, mtDNA abnormalities should be considered.
Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients
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Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients
Giuffrida M-, Tomasello F, Caraci F, Pandini G, Chiechio S, Battaglia G, De Bona P, Pappalardo G, Vigneri R, Nicoletti F, Rizzarelli E, Copani AG * A new function for beta-amyloid monomers(517 views) Society For Neuroscience Abstract Viewer And Itinerary Planner, 2011; 41: N/D-N/D. Impact Factor:0 ViewExport to BibTeXExport to EndNote