scholarly journals Diagnostic value of plasma neurofilament light: A multicentre validation study

2020 ◽  
Author(s):  
Nicholas Ashton ◽  
Shorena Janelidze ◽  
Ahmad Al Khleifat ◽  
Antoine Leuzy ◽  
Emma van der Ende ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Age Of Onset ◽  
Severe Depression ◽  
Diagnostic Value ◽  
Neurofilament Light ◽  
King's College ◽  
Age Related ◽  
Younger Age ◽  
Parkinsonian Disorders ◽  
Atypical Parkinsonian Disorders

Abstract Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in fifteen neurodegenerative diseases from two multicenter cohorts: King’s College London (n = 847) and the Swedish BioFINDER study (n = 1464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We further demonstrate that plasma NfL is clinically useful in identifying, i) atypical parkinsonian disorders in patients with parkinsonism, ii) dementia in individuals with Down Syndrome, iii) detect cases of frontotemporal dementia among psychiatric disorders such as moderate and severe depression, iv) identify frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related plasma NfL cut-offs for disorders with a younger age of onset. Finally, our findings suggest that plasma NfL performs best when a concentration cut-off is applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

scholarly journals A multicentre validation study of the diagnostic value of plasma neurofilament light

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas J. Ashton ◽  
Shorena Janelidze ◽  
Ahmad Al Khleifat ◽  
Antoine Leuzy ◽  
Emma L. van der Ende ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Neurodegenerative Disorders ◽  
Age Of Onset ◽  
Diagnostic Value ◽  
Neurofilament Light ◽  
King's College ◽  
Age Related ◽  
Younger Age ◽  
Parkinsonian Disorders ◽  
Atypical Parkinsonian Disorders

AbstractIncreased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King’s College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

scholarly journals Five reasons COVID-19 is less severe in younger age groups

2020 ◽  
Author(s):  
Paul W Turke
Keyword(s):  
Life History ◽  
Life History Theory ◽  
Age Of Onset ◽  
Age Groups ◽  
Medical Community ◽  
System Function ◽  
The Third ◽  
Immune System Function ◽  
Age Related ◽  
Younger Age

Abstract The severity of COVID-19 is age-related, with the advantage going to younger age groups. Five reasons are presented. The first two are well-known, are being actively researched by the broader medical community, and therefore are discussed only briefly here. The third, fourth, and fifth reasons derive from evolutionary life history theory, and potentially fill gaps in current understanding of why and how young and old age groups respond differently to infection with SARS-CoV-2. Age of onset of generalized somatic aging, and the timing of its progression, are identified as important causes of these disparities, as are specific antagonistic pleiotropic tradeoffs in immune system function.

Commentary on: psychotic symptoms in frontotemporal dementia: a diagnostic dilemma?

2015 ◽  
Vol 27 (4) ◽  
pp. 529-530 ◽  
Author(s):  
John T. O’brien
Keyword(s):  
Frontotemporal Dementia ◽  
Age Of Onset ◽  
Lewy Body Dementia ◽  
Psychotic Symptoms ◽  
Diagnostic Dilemma ◽  
Fused In Sarcoma ◽  
Symptom Profile ◽  
Younger Age ◽  
Neuropathological Diagnosis ◽  
Common Causes

Frontotemporal dementia is clearly a very important condition, not only because alongside Alzheimer's disease, vascular dementia, and Lewy body dementia it is one of the four most common causes of dementia, but because its broad symptom profile and younger age of onset makes it a particularly challenging condition to diagnose and manage. In recent years, great progress has been made in understanding genetic and pathological underpinnings of frontotemporal dementias, and in characterizing specific pathological causes. In particular, three major subtypes can be delineated: those associated pathologically with tau; transactive responsive DNA binding protein (TDP-43); or fused in sarcoma (FUS). Of these, tau and TDP-43 are by far the two most common subtypes of frontotemporal dementia. In addition, there have been important genetic advances and several autosomal dominant mutations have been described, for example associated with MAPT, progranulin, and C9ORF72. However, despite these important advances regarding pathophysiological heterogeneity, relatively little is known about the frequency, nature, and correlates of psychotic symptoms in the disorder. It is therefore very timely that in this month's Paper of the Month, Waldo and colleagues (Waldo et al., 2015) describe a very detailed description of a cohort of 97 consecutive subjects seen in Lund who received a neuropathological diagnosis of frontotemporal lobar degeneration.

scholarly journals Clinico-genetic findings in 509 frontotemporal dementia patients

2021 ◽  
Author(s):  
Matias Wagner ◽  
Georg Lorenz ◽  
Alexander E. Volk ◽  
Theresa Brunet ◽  
Dieter Edbauer ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Clinical Manifestation ◽  
Large Scale ◽  
Age Of Onset ◽  
Diagnostic Yield ◽  
Missense Variant ◽  
Disease Manifestation ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Biomarker Analysis

AbstractFrontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.

Smoking and treatment outcomes of neovascular age-related macular degeneration over 12 months

2019 ◽  
Vol 104 (7) ◽  
pp. 893-898
Author(s):  
Harshil Dharamdasani Detaram ◽  
Nichole Joachim ◽  
Gerald Liew ◽  
Kim Van Vu ◽  
George Burlutsky ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Treatment Outcomes ◽  
Age Of Onset ◽  
Smoking Status ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Younger Age ◽  
Never Smokers ◽  
Endothelial Growth Factor

BackgroundTo assess the association of smoking with age of onset of neovascular age-related macular degeneration (nAMD), visual acuity (VA), central macular thickness (CMT) and the presence of fluid in patients with nAMD.Methods547 patients with nAMD were recruited from a tertiary eye clinic during 2012–2015; of these, 490 patients were followed up 12 months later. Clinical diagnosis of nAMD was confirmed by a retinal specialist. Smoking was determined from self-reported history as never, past or current. Age of onset was defined as date of first recorded diagnosis of nAMD in either eye or date of first anti-vascular endothelial growth factor injection. CMT and presence of fluid were recorded from spectral-domain optical coherence tomography images. VA was recorded as number of letters read at 3 m.ResultsAfter multivariable adjustment, current smokers developed nAMD at an average 5.5 years younger age than never smokers and 4.4 years younger age than past smokers (p<0.0001 and p=0.0008, respectively). At baseline, adjusted mean CMT was significantly higher in current compared with past smokers (259.2 µm vs 231.9 µm, respectively, p=0.04). Current smokers versus never smokers had greater odds of presence of subretinal fluid at 12-month follow-up: multivariable-adjusted OR 1.99 (95% CI 1.09 to 3.67). Smoking status was not significantly associated with VA over 12 months.ConclusionsCurrent smoking was associated with a younger age of nAMD onset and key treatment outcomes such as higher mean CMT and greater odds of subretinal fluid presence. These findings suggest that smoking cessation may benefit patients being treated for nAMD.

Bladder dysfunction in IPD and atypical Parkinsonian disorders – pathophysiology and treatment

2005 ◽  
Vol 32 (06) ◽  
Author(s):  
K Winge ◽  
H Stimpel ◽  
KK Nielsen ◽  
L Friberg ◽  
L Werdelin
Keyword(s):  
Bladder Dysfunction ◽  
Parkinsonian Disorders ◽  
Atypical Parkinsonian Disorders

scholarly journals Depression, anxiety and stress among patients with inflammatory bowel disease during the COVID-19 pandemic: Australian national survey

2021 ◽  
Vol 8 (1) ◽  
pp. e000581
Author(s):  
Madiha Cheema ◽  
Nikola Mitrev ◽  
Leanne Hall ◽  
Maria Tiongson ◽  
Golo Ahlenstiel ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Severe Depression ◽  
Chronic Illnesses ◽  
Electronic Survey ◽  
Validated Questionnaire ◽  
Younger Age ◽  
Modifiable Factors ◽  
High Prevalence ◽  
Inflammatory Bowel

BackgroundThe global COVID-19 pandemic has impacted on the mental health of individuals, particularly those with chronic illnesses. We aimed to quantify stress, anxiety and depression among individuals with Inflammatory bowel disease (IBD) in Australia during the pandemic.MethodsAn electronic survey was made available to IBD patients Australia-wide from 17 June to 12 July 2020. Respondents with an underlying diagnosis of IBD and over 18 years of age were included. A validated questionnaire (Depression, Anxiety, Stress Score-21, DASS21) was used to assess depression, anxiety and stress. Data on potential predictors of depression, anxiety and stress were collected.Results352 participated in the survey across Australia. 60.5% of respondents fulfilled DASS criteria for at least moderate depression, anxiety or stress. 45% reported a pre-existing diagnosis of depression and/or anxiety. Over 2/3 of these respondents reported worsening of their pre-existing depression/anxiety due to the current pandemic. Of those without a pre-existing diagnosis of anxiety or depression, high rates of at least moderate to severe depression (34.9%), anxiety (32.0%) and stress (29.7%) were noted. Younger age (OR 0.96, 95% CI 0.94 to 0.98, p<0.001), lack of access to an IBD nurse (OR 1.81, 95% CI 1.03 to 3.19, p=0.04) and lack of education on reducing infection risk (OR 1.99, 95% CI 1.13 to 3.50, p=0.017) were associated with significant stress, anxiety and/or depression.ConclusionHigh prevalence of undiagnosed depression, anxiety and stress was identified among respondents. Improved access to IBD nurse support and greater attention to education are modifiable factors that may reduce depression, anxiety and/or stress among patients with IBD during the pandemic.

scholarly journals The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Madison E. Hoes ◽  
Anastazja M. Gorecki ◽  
Frances Theunissen ◽  
Abigail L. Pfaff ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Symptom Onset ◽  
Disease Risk ◽  
Age Of Onset ◽  
Sequencing Analysis ◽  
Age Related ◽  
Australian Cohort ◽  
Progression Markers ◽  
Age Related Cognitive Decline

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.

Caribbean parkinsonism and other atypical Parkinsonian disorders

2004 ◽  
Vol 10 ◽  
pp. S19-S26 ◽  
Author(s):  
Eduardo Tolosa ◽  
Daniela Calandrella ◽  
Marisol Gallardo
Keyword(s):  
Parkinsonian Disorders ◽  
Atypical Parkinsonian Disorders
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