Blood TDP-43 Combined with Demographics Information Predicts Dementia Occurrence in Community Non-Dementia Elderly

2021 ◽  
Vol 79 (1) ◽  
pp. 301-309
Author(s):  
Lin Sun ◽  
Wei Li ◽  
Ling Yue ◽  
Shifu Xiao
Keyword(s):  
Cognitive Function ◽  
Dna Binding Protein ◽  
Blood Levels ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Dementia Patients ◽  
Relationship Of ◽  
The Relationship

Background: TAR DNA-binding protein-43 (TDP-43) and neurofilament light chain (NfL) are promising fluid biomarkers of disease progression for various dementia. Objective: We would explore whether blood levels of NfL and TDP-43 could predict the long-term progression to dementia, and the relationship of TDP-43 levels between cerebrospinal fluid (CSF) and blood. Methods: A total of 86 non-dementia elderly received 7-year follow-up, and were divided into 49 stable normal control (NC)/mild cognitive impairment (MCI) subjects, 19 subjects progressing from NC to MCI, and 18 subjects progressing from NC/MCI to dementia. Blood TDP-43 and NfL levels, and cognitive functions were measured in all subjects. Furthermore, another cohort of 23 dementia patients, including 13 AD and 10 non-AD patients received blood and CSF measurements of TDP-43. Results: In cohort 1, compared to stable NC/MCI group, there were higher levels of blood TDP-43 at baseline in subjects progressing from NC/MCI to dementia. The combination of baseline blood TDP-43 levels with demographics including age, education, and diabetes had the detection for dementia occurrence. Baseline blood levels of NfL are negatively associated with cognitive function at 7-year follow-up. In cohort 2, we found there were no relationship between CSF and blood levels of TDP-43. Moreover, the levels of TDP-43 in CSF was positively associated with the age of patients, especially in AD group. Conclusion: Single blood TDP-43 could not estimate dementia occurrence; however, TDP-43 combined with demographics has the predictive effect for dementia occurrence and NfL level is associated with a decrease of cognitive function.

Syndactyly—A Review and Long Term Results

HAND ◽  
1977 ◽  
Vol os-9 (1) ◽  
pp. 16-27 ◽  
Author(s):  
Peter M. Brown
Keyword(s):  
Surgical Treatment ◽  
Long Term Results ◽  
Anatomical Distribution ◽  
Long Term Follow Up ◽  
Relationship Of ◽  
The Relationship ◽  
Results Of Surgery

Syndactyly is classified and the principles of its surgical treatment discussed. The notes of eighty-five patients who had 222 webs between them were reviewed. A long term follow-up was carried out on thirty-two of these patients who had seventy-six clefts separated. The sexual and anatomical distribution of the syndactyly was investigated. The results of surgery were assessed including complications, and the relationship of complications to the type of graft used and the age at operation. It is suggested that complicated syndactyly is often separated at too early an age.

Focal Psychotherapy: Its Potential Impact on Psychotherapeutic Practice in Medicine

1972 ◽  
Vol 3 (4) ◽  
pp. 311-325 ◽  
Author(s):  
Paul H. Ornstein ◽  
Anna Ornstein
Keyword(s):  
Treatment Process ◽  
Practitioner Training ◽  
Therapeutic Results ◽  
Complete Treatment ◽  
Short And Long Term ◽  
Potential Impact ◽  
Relationship Of ◽  
The Relationship

A condensed illustration of a complete treatment process of “focal psychotherapy” is presented to contrast the specificity of this form of psychotherapy with nonspecific approaches. A two-year follow-up illustrates the meaning of specificity. The relationship of therapeutic results to the focal interventions is reflected in the patient's own views of his accomplishments in therapy. The theory and techniques of focal psychotherapy were originally worked out by Balint and his co-workers. The case example presented here is the basis of discussion showing how focal psychotherapy can help re-conceptualize and add precision to the theory, techniques and processes of both short- and long-term psychoanalytic psychotherapy. Such increased precision in interventions and focal aims could help leaders and general practitioner training groups to better achieve their collaborative tasks.

scholarly journals 1118 Examining the Role of Serum and Exosomal Biomarkers in Symptoms of Fatigue and Daytime Sleepiness Following Traumatic Brain Injury

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A426-A426
Author(s):  
J J Leete ◽  
C L Pattinson ◽  
V A Guedes ◽  
C Lai ◽  
C Devoto ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Single Molecule ◽  
Daytime Sleepiness ◽  
Blood Levels ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Ultrasensitive Assay ◽  
Fatigue Severity ◽  
The Relationship

Abstract Introduction Fatigue and daytime sleepiness are two of the most common chronic symptoms reported after traumatic brain injury (TBI). However, there is limited understanding of the pathophysiological mechanisms following TBI that result in these symptoms. Previous research has observed elevations in peripheral blood levels of proteins in TBI patients versus controls, including neurofilament light chain (NFL)—predominantly expressed in long myelinated subcortical axons—and glial fibrillary acidic protein (GFAP)—predominantly expressed in reactive astrocytes responding to central nervous system injuries. This study examines the relationship between serum and exosomal NFL and GFAP, and symptoms of fatigue and daytime sleepiness in TBI patients 1-year after injury. Methods Sixty-seven patients with TBIs ranging from mild to severe were included in this study. Blood samples were collected from all participants 1-year post TBI, with concentrations of GFAP and NFL measured in serum and exosomes using Single Molecule Array technology (Simoa), an ultrasensitive assay. Participants reported fatigue using the Fatigue Severity Scale (FSS), and daytime sleepiness using the Epworth Sleepiness Scale (ESS). Results A linear regression model of fatigue symptoms and exosomal NFL controlling for age revealed that fatigue was negatively associated with exosomal NFL concentrations (β = -.317, p = .041, ηp2 = -.343) and accounted for 20.2% of the change in NFL. Serum NFL concentrations were not associated with fatigue, nor were GFAP serum or exosomes. No significant associations were found between NFL, GFAP, and daytime sleepiness. Conclusion Our findings suggest that exosomal NFL may be related to mechanisms underlying TBI-related fatigue and the potential of NFL as a biomarker of fatigue. To our knowledge, this study is the first to examine the relationship between post-TBI NFL levels and fatigue symptoms. Further investigation into serum and exosome biomarkers of TBI-related fatigue and daytime sleepiness is warranted. Support National Institutes of Health and Center for Neuroscience and Regenerative Medicine

scholarly journals Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

2021 ◽  
Vol 14 ◽  
pp. 175628642110576
Author(s):  
Kimberley Allen-Philbey ◽  
Stefania De Trane ◽  
Zhifeng Mao ◽  
Cesar Álvarez-González ◽  
Joela Mathews ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Stage ◽  
Neurofilament Light Chain ◽  
Skin Reactions ◽  
Neurofilament Light ◽  
Disability Status ◽  
Walking Tests ◽  
Grade 3

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data ( n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data ( n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

scholarly journals The Relationship of Soluble TREM2 to Other Biomarkers of Sporadic Alzheimer’s Disease

2021 ◽  
Author(s):  
So-Hee Park ◽  
Eun-Hye Lee ◽  
Hyung-Ji Kim ◽  
Sungyang Jo ◽  
Sunju Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
Medical Center ◽  
Clinical Status ◽  
Inverse Correlation ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Relationship Of ◽  
The Relationship

Abstract Microglial activation is a central player in the pathophysiology of Alzheimer’s disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD.Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF.In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age.Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.

scholarly journals Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias

Neurology ◽  
2017 ◽  
Vol 88 (10) ◽  
pp. 961-969 ◽  
Author(s):  
Petra Steinacker ◽  
Elisa Semler ◽  
Sarah Anderl-Straub ◽  
Janine Diehl-Schmid ◽  
Matthias L. Schroeter ◽  
...  
Keyword(s):  
Functional Decline ◽  
Disease Status ◽  
Longitudinal Change ◽  
Blood Levels ◽  
Phosphorylated Tau ◽  
Left Frontal Lobe ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Primary Progressive

Objective:To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants.Methods:We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), β-amyloid (Aβ1-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy.Results:Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Aβ1-42achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA.Conclusions:Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative.Classification of evidence:This study provides Class I evidence that in patients with PPA, blood levels of NF-L can distinguish the logopenic variant from the nonfluent/agrammatic and semantic variants.

scholarly journals The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
So-Hee Park ◽  
Eun-Hye Lee ◽  
Hyung-Ji Kim ◽  
Sungyang Jo ◽  
Sunju Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
Medical Center ◽  
Clinical Status ◽  
Inverse Correlation ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Relationship Of ◽  
The Relationship

AbstractMicroglial activation is a central player in the pathophysiology of Alzheimer’s disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.

Abstract 248: Baseline Cognitive Impairment a Predictor of Mortality in Cardiovascular Disease

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Antonio D Lassaletta ◽  
Frank W Sellke ◽  
Ronald A Cohen
Keyword(s):  
Cardiovascular Disease ◽  
Executive Function ◽  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Independent Living ◽  
Cognitive Domains ◽  
The Relationship

Objective: Few longitudinal studies have examined outcomes of patients with cardiovascular disease (CVD) in relation to earlier, baseline cognitive function, or examined the relationship between specific cognitive domains and mortality. This study attempted to clarify the relationship between cognitive function and long-term outcomes, particularly mortality, in patients with cardiovascular disease. Methods: One hundred seventy seven participants between 55 and 85 years of age with an established history CVD were recruited from healthcare institutions. A comprehensive neurophysiological test battery was administered to all patients at baseline assessing 4 cognitive domains: language, visual-spatial, memory, and attention-executive function. Composite scores were calculated by averaging z-scores of all component measures. At 6-year the follow-up, of the 136 patients who were still enrolled, the 116 who were still alive were contacted by phone for assessment of level of independent living, and subjective assessment of cognitive function, and quality of life.Results were corrected for age. Results: At follow-up, participants who were deceased had significantly lower baseline attention-executive function (M=-0.51, SD=0.78 vs. M=0.06, SD=0.54 in survivors, p < 0.01). Poorer memory performance at baseline was associated with a greater degree of cognitive dysfunction at follow-up (p = 0.085). No significant relationships were found between baseline cognitive performance and independent living status or quality of life. Conclusion: Impaired executive function was predictive of poorer outcomes, specifically, 6-year mortality. This finding reinforces the frontal nature of vascular cognitive impairments, especially in regard to the long term sequelae of cognitive dysfunction in patients with CVD. The higher mortality observed in patients with baseline executive domain impairment may be due to behaviors such as impaired self-care, treatment adherence and rehab participation or functional impairments that exacerbate health problems, resulting in death. Patients with cardiovascular disease and executive function impairment should be identified and measures taken to address these potential problems.

scholarly journals Is Persistent Visual Neglect Associated with Poor Survival?

2010 ◽  
Vol 2 ◽  
pp. JCNSD.S5539
Author(s):  
M. Jehkonen ◽  
M. Laihosalo ◽  
T. Saunamäki ◽  
A-M. Koivisto ◽  
P. Dastidar ◽  
...  
Keyword(s):  
Right Hemisphere ◽  
Limited Attention ◽  
Visual Neglect ◽  
Poor Survival ◽  
Additional Information ◽  
Poor Recovery ◽  
Relationship Of ◽  
The Relationship

Background The association of visual neglect with survival after right hemisphere (RH) stroke has received only limited attention. Objective This study explores the relationship of visual neglect and its spontaneous recovery to survival in a homogenous patient group with first-ever RH stroke. Methods Fifty-one RH stroke patients who suffered an infarct between 1994 and 1997 were retrospectively followed for survival until August 31, 2009. Acute-phase neurological, neuropsychological and neuroradiological data were studied to identify predictors of survival. Results Twenty-eight patients died during the follow-up. Age, education, and poor recovery of visual neglect emerged as significant single predictors of death. The best set of predictors for poor survival in the multivariate model was poor recovery of visual neglect and low education. Conclusions Poor recovery of visual neglect is associated with long-term mortality in RH infarct patients. The follow-up of RH patients’ neuropsychological performance gives additional information about the prognosis.

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