scholarly journals Amyloid‐positive individuals with subjective cognitive decline present increased CSF neurofilament light levels that relate to hippocampal volume

2020 ◽  
Vol 16 (S6) ◽  
Author(s):  
Gonzalo Sánchez‐Benavides ◽  
Marc Suárez‐Calvet ◽  
Marta Milà‐Alomà ◽  
Eider M. Arenaza‐Urquijo ◽  
Oriol Grau‐Rivera ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline ◽  
Neurofilament Light ◽  
Light Levels

scholarly journals Amyloid-β positive individuals with subjective cognitive decline present increased CSF Neurofilament Light levels that relates to lower hippocampal volume

2021 ◽  
Author(s):  
Gonzalo Sánchez-Benavides ◽  
Marc Suárez-Calvet ◽  
Marta Milà-Alomà ◽  
Eider M. Arenaza-Urquijo ◽  
Oriol Grau-Rivera ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Amyloid Β ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline ◽  
Neurofilament Light ◽  
Light Levels

scholarly journals Postoperative delirium is associated with increased plasma neurofilament light

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Cameron P Casey ◽  
Heidi Lindroth ◽  
Rosaleena Mohanty ◽  
Zahra Farahbakhsh ◽  
Tyler Ballweg ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Postoperative Delirium ◽  
Neuronal Injury ◽  
Dose Dependence ◽  
Hippocampal Volume ◽  
Mean Difference ◽  
Neurofilament Light ◽  
Light Levels ◽  
Potential Marker

Abstract While delirium is associated with cognitive decline and dementia, there is limited evidence to support causality for this relationship. Clarification of how delirium may cause cognitive decline, perhaps through evidence of contemporaneous neuronal injury, would enhance plausibility for a causal relationship. Dose-dependence of neuronal injury with delirium severity would further enhance the biological plausibility for this relationship. We tested whether delirium is associated with neuronal injury in 114 surgical patients recruited to a prospective biomarker cohort study. Patients underwent perioperative testing for changes in neurofilament light, a neuronal injury biomarker, as well as a panel of 10 cytokines, with contemporaneous assessment of delirium severity and incidence. A subset of patients underwent preoperative MRI. Initially we confirmed prior reports that neurofilament light levels correlated with markers of neurodegeneration [hippocampal volume (ΔR2 = 0.129, P = 0.015)] and white matter changes including fractional anisotropy of white matter (ΔR2 = 0.417, P < 0.001) with similar effects on mean, axial and radial diffusivity) in our cohort and that surgery was associated with increasing neurofilament light from preoperative levels [mean difference (95% confidence interval, CI) = 0.240 (0.178, 0.301) log10 (pg/ml), P < 0.001], suggesting putative neuronal injury. Next, we tested the relationship with delirium. Neurofilament light rose more sharply in participants with delirium compared to non-sufferers [mean difference (95% CI) = 0.251 (0.136, 0.367) log10 (pg/ml), P < 0.001]. This relationship showed dose-dependence, such that neurofilament light rose proportionately to delirium severity (ΔR2 = 0.199, P < 0.001). Given that inflammation is considered an important driver of postoperative delirium, next we tested whether neurofilament light, as a potential marker of neurotoxicity, may contribute to the pathogenesis of delirium independent of inflammation. From a panel of 10 cytokines, the pro-inflammatory cytokine IL-8 exhibited a strong correlation with delirium severity (ΔR2 = 0.208, P < 0.001). Therefore, we tested whether the change in neurofilament light contributed to delirium severity independent of IL-8. Neurofilament light was independently associated with delirium severity after adjusting for the change in inflammation (ΔR2 = 0.040, P = 0.038). These data suggest delirium is associated with exaggerated increases in neurofilament light and that this putative neurotoxicity may contribute to the pathogenesis of delirium itself, independent of changes in inflammation.

IC-P-138: High CSF TAU is Related to Reduced Hippocampal Volume and Subjective Cognitive Decline in Healthy Elderly With Amyloid Pathology

2016 ◽  
Vol 12 ◽  
pp. P102-P103
Author(s):  
Alexa Pichet Binette ◽  
Jacob W. Vogel ◽  
Vladimir S. Fonov ◽  
Cécile Madjar ◽  
Jennifer Tremblay-Mercier ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline ◽  
Amyloid Pathology ◽  
Healthy Elderly

scholarly journals Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment

2019 ◽  
Vol 75 (7) ◽  
pp. 1382-1392 ◽  
Author(s):  
Marie Caillaud ◽  
Carol Hudon ◽  
Benjamin Boller ◽  
Simona Brambati ◽  
Simon Duchesne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Episodic Memory ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline

Abstract Objective The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer’s disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. Method We included 126 participants from the Consortium for the Early Identification of Alzheimer’s disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). Results Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. Discussion As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD’s hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.

scholarly journals The Interplay Between Gray Matter and White Matter Neurodegeneration in Subjective Cognitive Decline

2020 ◽  
Author(s):  
Nira Cedres ◽  
Patricia Diaz-Galvan ◽  
Lucio Diaz-Flores ◽  
J-Sebastian Muehlboeck ◽  
Yaiza Molina ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Gray Matter ◽  
Mean Diffusivity ◽  
Occipital Lobe ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline ◽  
Community Based ◽  
Cortical Thinning ◽  
Behavioral Marker

Abstract AIMS: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM. METHODS: We included 225 cognitively unimpaired individuals from a community-based cohort, of whom 123 endorsed one or more subjective cognitive complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration.RESULTS: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to the complaints, but the contribution of cortical thinning to SCD was stronger.CONCLUSIONS: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer’s disease (AD). Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.

scholarly journals The implications of different approaches to define AT(N) in Alzheimer disease

Neurology ◽  
2020 ◽  
Vol 94 (21) ◽  
pp. e2233-e2244 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Antoine Leuzy ◽  
Shorena Janelidze ◽  
Sebastian Palmqvist ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Clinical Stage ◽  
Hippocampal Volume ◽  
Cognitively Impaired ◽  
Amyloid Pet ◽  
Prognostic Information ◽  
Neurofilament Light ◽  
Amyloid Aβ ◽  
Tau Pet

ObjectiveTo compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies.MethodsA total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 participants from BioFINDER-2 (245 CU and 144 CI [138 MCI and 6 AD dementia]). Biomarkers for A were CSF Aβ42 and amyloid-PET ([18F]flutemetamol); for T, CSF phosphorylated tau (p-tau) and tau PET ([18F]flortaucipir); and for (N), hippocampal volume, temporal cortical thickness, and CSF neurofilament light (NfL). Binarization of biomarkers was achieved using cutoffs defined in other cohorts. The relationship between different AT(N) combinations and cognitive trajectories (longitudinal Mini-Mental State Examination scores) was examined using linear mixed modeling and coefficient of variation.ResultsAmong CU participants, A−T−(N)− or A+T−(N)− variants were most common. However, more T+ cases were seen using p-tau than tau PET. Among CI participants, A+T+(N)+ was more common; however, more (N)+ cases were seen for MRI measures relative to CSF NfL. Tau PET best predicted longitudinal cognitive decline in CI and p-tau in CU participants. Among CI participants, continuous T (especially tau PET) and (N) measures improved the prediction of cognitive decline compared to binary measures.ConclusionsOur findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage. In some cases, dichotomizing biomarkers may result in loss of important prognostic information.

scholarly journals Basal Forebrain Atrophy Is Associated With Allocentric Navigation Deficits in Subjective Cognitive Decline

2021 ◽  
Vol 13 ◽  
Author(s):  
Qian Chen ◽  
Sichu Wu ◽  
Xin Li ◽  
Yi Sun ◽  
Wenqian Chen ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Basal Forebrain ◽  
Hippocampal Volume ◽  
Structural Basis ◽  
Subjective Cognitive Decline ◽  
Intracranial Volume ◽  
Spatial Disorientation ◽  
Mri Volumetry ◽  
Magnetic Resonance Imaging Mri ◽  
And Control

Individuals with subjective cognitive decline (SCD) are at higher risk of incipient Alzheimer's disease (AD). Spatial navigation (SN) impairments in AD dementia and mild cognitive impairment patients have been well-documented; however, studies investigating SN deficits in SCD subjects are still lacking. This study aimed to explore whether basal forebrain (BF) and entorhinal cortex (EC) atrophy contribute to spatial disorientation in the SCD stage. In total, 31 SCD subjects and 24 normal controls were enrolled and administered cognitive scales, a 2-dimensional computerized SN test, and structural magnetic resonance imaging (MRI) scanning. We computed the differences in navigation distance errors and volumes of BF subfields, EC, and hippocampus between the SCD and control groups. The correlations between MRI volumetry and navigation distance errors were also calculated. Compared with the controls, the SCD subjects performed worse in both egocentric and allocentric navigation. The SCD group showed volume reductions in the whole BF (p < 0.05, uncorrected) and the Ch4p subfield (p < 0.05, Bonferroni corrected), but comparable EC and hippocampal volumes with the controls. In the SCD cohort, the allocentric errors were negatively correlated with total BF (r = −0.625, p < 0.001), Ch4p (r = −0.625, p < 0.001), total EC (r = −0.423, p = 0.031), and left EC volumes (r = −0.442, p = 0.024), adjusting for age, gender, years of education, total intracranial volume, and hippocampal volume. This study demonstrates that SN deficits and BF atrophy may be promising indicators for the early detection of incipient AD patients. The reduced BF volume, especially in the Ch4p subfield, may serve as a structural basis for allocentric disorientation in SCD subjects independent of hippocampal atrophy. Our findings may have further implications for the preclinical diagnosis and intervention for potential AD patients.

A-4 Cerebrospinal Fluid and Plasma Neurofilament Light in Relation to Longitudinal Objective and Subjective Cognitive Decline in Older Adults

2021 ◽  
Vol 36 (6) ◽  
pp. 1043-1043
Author(s):  
Natalie A Thwaites ◽  
Omair A Khan ◽  
Dandan Liu ◽  
Marilyn Steinbach ◽  
Camdyn Gilbert ◽  
...  
Keyword(s):  
Older Adults ◽  
Cerebrospinal Fluid ◽  
Executive Functioning ◽  
Cognitive Decline ◽  
Cognitive Aging ◽  
Interactive Effects ◽  
Subjective Cognitive Decline ◽  
Blood Draw ◽  
Neurofilament Light ◽  
P Values

Abstract Objective Cerebrospinal fluid (CSF) and plasma neurofilament light (NFL) concentrations were assessed in relation to longitudinal objective and subjective cognitive outcomes in older adults ranging from normal cognition to mild cognitive impairment. Interactive effects were assessed for apolipoprotein E ϵ4 (APOE4) carriership, a strong genetic risk factor for Alzheimer’s disease and molecular moderator of vascular disease. Method Vanderbilt Memory & Aging Project participants (CSF n = 149, 72 ± 6 years; plasma n = 333, 73 ± 7 years) underwent fasting blood draw and lumbar puncture at baseline for NFL quantification. Serial neuropsychological assessments and subjective cognitive decline (SCD) questionnaires were completed at 18-month increments. Linear mixed effects regression models adjusted for age, sex, race/ethnicity, education, APOE4 carriership (for main effect models), and depressed mood. NFL x APOE4 interaction terms were used as predictors in follow-up models. Results CSF NFL predicted steeper declines in an executive functioning composite score (β = −0.0001, p = 0.001) and WAIS-IV Coding (β = −0.001, p = 0.001). An APOE4 interaction was present for executive functioning (β = −0.0002, p = 0.005) such that CSF NFL associations with longitudinal decline were stronger among APOE4+ participants. Plasma NFL predicted worsening SCD (β = 0.27, p = 0.002) and objective cognitive decline across all domains (p-values <0.05), with multiple APOE4 interactions (p-values <0.05) suggesting stronger associations with objective cognitive decline among APOE4+ participants. Conclusions Both CSF and plasma NFL detect neuropathology associated with cognitive decline among non-demented older adults, especially among APOE4 carriers. Findings further support the value of SCD as reflecting neurodegenerative changes associated with accelerated cognitive aging.

P3-274: High CSF TAU is Related to Reduced Hippocampal Volume and Subjective Cognitive Decline in Healthy Elderly with Amyloid Pathology

2016 ◽  
Vol 12 ◽  
pp. P939-P940
Author(s):  
Alexa Pichet Binette ◽  
Jacob W. Vogel ◽  
Vladimir S. Fonov ◽  
Jennifer Tremblay-Mercier ◽  
Cécile Madjar ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline ◽  
Amyloid Pathology ◽  
Healthy Elderly

scholarly journals Blood NCAPH2 Methylation Is Associated With Hippocampal Volume in Subjective Cognitive Decline With Apolipoprotein E ε4 Non-carriers

2021 ◽  
Vol 13 ◽  
Author(s):  
Ying Chen ◽  
Tao-Ran Li ◽  
Shu-Wen Hao ◽  
Xiao-Ni Wang ◽  
Yan-Ning Cai ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Apolipoprotein E ◽  
Early Stage ◽  
Structural Mri ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline ◽  
Cognitively Normal ◽  
Apoe Ε4 ◽  
Neuropsychological Assessments ◽  
Normal Controls

Objective: This study assessed the methylation of peripheral NCAPH2 in individuals with subjective cognitive decline (SCD), identified its correlation with the hippocampal volume, and explored whether the correlation is influenced by apolipoprotein E ε4 (APOE ε4) status.Methods: Cognitively normal controls (NCs, n = 56), individuals with SCD (n = 81), and patients with objective cognitive impairment (OCI, n = 51) were included from the Sino Longitudinal Study on Cognitive Decline (NCT03370744). All participants completed neuropsychological assessments, blood tests, and structural MRI. NCAPH2 methylation was compared according to the diagnostic and APOE ε4 status. Partial correlation analysis was conducted to assess the correlations between the hippocampal volume, cognitive tests, and the NCAPH2 methylation levels.Results: Individuals with SCD and patients with OCI showed significantly lower levels of NCAPH2 methylation than NCs, which were independent of the APOE ε4 status. The NCAPH2 methylation levels and the hippocampal volumes were positively correlated in the SCD APOE ε4 non-carriers but not in the OCI group. No association was found between the NCAPH2 methylation levels and the cognitive function.Conclusion: Abnormal changes in blood NCAPH2 methylation were found to occur in SCD, indicating its potential to be used as a useful peripheral biomarker in the early stage of Alzheimer's disease screening.

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