Sleep and Tau Pathology in Vietnam War Veterans with Preclinical and Prodromal Alzheimer’s Disease

Background: The increasing prevalence of Alzheimer’s disease (AD) and lack of effective medications has led to a need to identify modifiable risk factors as targets for interventions. Objective: In this cross-sectional study, we sought to determine whether worse sleep quality is associated with increased pathological tau, and whether this relationship is affected by amyloid pathology. Methods: 66 male participants underwent Florbetapir (AV45) positron emission tomography (PET) and Flortaucipir (FTP) PET and completed the Pittsburgh Sleep Quality Index questionnaire (PSQI) as part of the Department of Defense Alzheimer’s Disease Neuroimaging Initiative, a multicenter study collecting data from Vietnam War veterans, some of whom have a history of post-traumatic stress disorder, or non-penetrating traumatic brain injury. AV45 PET was used to determine the presence of significant amyloid pathology. We used regression models to determine the effects of amyloid pathology and PSQI on tau deposition in brain regions associated with Braak stages. Results: Among the 66 participants, 14 individuals were amyloid positive (21%) and 52 were amyloid negative (79%). In regions associated with Braak stages III-IV, there was a significant interaction of amyloid status on PSQI (β= 0.04, p = 0.003) with higher PSQI correlating with higher FTP SUVr in amyloid-positive individuals only (β= 0.031, p = 0.005). Conclusion: Our study found that an AD profile of tau deposition was associated with an interaction between self-reported sleep quality and amyloid pathology such that worse self-reported sleep was related to higher tau in regions usually associated with AD progression, but only in individuals with high cerebral amyloid deposition.

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Sleep and Tau Pathology in Vietnam War Veterans with Preclinical and Prodromal Alzheimer’s Disease

10.21203/rs.3.rs-32083/v1 ◽

2020 ◽

Author(s):

Murray John Andrews ◽

Ryan Ross ◽

Atul Malhotra ◽

Sonia Ancoli-Israel ◽

James Brewer ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sleep Quality ◽

Vietnam War ◽

Standardized Uptake Value ◽

Post Traumatic Stress ◽

War Veterans ◽

Cross Sectional ◽

Amyloid Pathology ◽

Vietnam War Veterans

Abstract Background The increasing prevalence of Alzheimer’s Disease (AD) and lack of effective medications has led to a need to identify modifiable risk factors as targets for interventions. In this cross-sectional study, we sought to determine whether worse sleep quality is associated with increased pathological tau, and whether this relationship is affected by amyloid pathology. Methods 66 male participants underwent Florbetapir (AV45) Positron Emission Tomography (PET), Flortaucipir (FTP) PET and completed the Pittsburgh Sleep Quality Index questionnaire (PSQI) as part of the Department of Defense Alzheimer’s Disease Neuroimaging Initiative, a multicenter study collecting data from Vietnam War veterans, some of whom have a history of Post-Traumatic Stress Disorder (PTSD), or non-penetrating Traumatic Brain Injury (TBI). AV45 PET was used to determine the presence of significant amyloid pathology, and t-tests were used to assess differences in tau deposition in Braak regions associated with AD progression between amyloid positive and amyloid negative individuals. We used regression models to determine the effects of amyloid pathology and PSQI on tau deposition in Braak regions. Results Among the 66 participants, the average (SD) age was 71.04 (0.99) years. 14 individuals were amyloid positive (21%), and 52 were amyloid negative (79%). The amyloid positive and amyloid negative groups did not differ in tau in the regions investigated. There were no significant main effects of amyloid status or PSQI on FTP Standardized Uptake Value ratio (SUVr) in any of the regions investigated. However, in Braak stages III-IV, there was a significant interaction of amyloid status on PSQI (β = 0.039, p = 0.035) with higher PSQI correlating with higher FTP SUVr in amyloid-positive individuals only (β = 0.031, p = 0.017). Conclusions Our study found that an AD profile of tau deposition was associated with an interaction between self-reported sleep quality and amyloid pathology such that worse self-reported sleep was related to higher tau in regions associated with AD progression, but only in individuals with high cerebral amyloid deposition. Our study suggests that sleep quality may be a modifiable risk factor in preclinical and prodromal populations of AD.

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Plasma neurofilament light and cerebrospinal fluid biomarkers are associated with white matter damage in Alzheimer's disease

10.21203/rs.3.rs-115308/v1 ◽

2020 ◽

Author(s):

Fardin Nabizadeh ◽

Mohammad Balabandian ◽

Mohammad Reza Rostami ◽

Samuel Berchi Kankam

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Diffusion Tensor ◽

Brain Regions ◽

Csf Biomarkers ◽

Cross Sectional ◽

Neurofilament Light ◽

Microstructural Changes ◽

Cerebrospinal Fluid Biomarkers

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration largely, and synaptic damage in AD. However, there is no investigation of the association between plasma NFL and white matter microstructure integrity. we have investigated the cross-sectional associations of plasma NFL, CSF tau, p tau, and Aβ with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, CSF total tau, CSF p tau, and as well as CSF Aβ, separately using a partial correlation model controlled for the effect of age, sex and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL has a negative correlation with FA and positive correlation with RD, AD, and MD values in different regions. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and for MCI progression to AD.

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Testimonial: Impact of Alzheimer's Disease on One Artist's Body of Work

CNS Spectrums ◽

10.1017/s1092852900002868 ◽

2008 ◽

Vol 13 (S2) ◽

pp. 19-20 ◽

Cited By ~ 1

Author(s):

Patricia Utermohlen

Keyword(s):

Alzheimer’S Disease ◽

Vietnam War ◽

Family Life ◽

Fine Arts ◽

Bachelor's Degree ◽

War Veterans ◽

University Of Oxford ◽

Vietnam War Veterans ◽

The University ◽

Pennsylvania Academy

William Utermohlen was born in 1933. Upon completing his Bachelor's degree at the Pennsylvania Academy of Fine Arts, he joined the Army and then moved to England to study at the University of Oxford. This is where he met his wife, Patricia. Bill painted scenes from his childhood in Philadelphia, images of Vietnam War veterans, and pictures inspired by Dante's Inferno. Later, many of his paintings depicted family life, conversations with friends, and his home—they were happy pictures.

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O4-09-06: Extensive amyloid pathology in remote brain regions may predict hypometabolism in functionally connected brain regions with minor amyloid pathology: An Alzheimer's disease study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1688 ◽

2012 ◽

Vol 8 (4S_Part_17) ◽

pp. P633-P633

Author(s):

Elisabeth Klupp ◽

Stefan Förster ◽

Timo Grimmer ◽

Masoud Tahmasian ◽

Behrooz Yousefi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Regions ◽

Amyloid Pathology ◽

Disease Study

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KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease

Nature Communications ◽

10.1038/s41467-021-23755-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Julia Neitzel ◽

Nicolai Franzmeier ◽

Anna Rubinski ◽

Martin Dichgans ◽

Matthias Brendel ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Regions ◽

Protective Role ◽

Amyloid Pet ◽

Tau Pathology ◽

Cross Sectional ◽

Memory Impairments ◽

Amyloid A ◽

Tau Pet

AbstractKlotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShet is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShet and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VShet showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VShet on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VShet was related to better memory functions in amyloid-positive participants and this association was mediated by lower tau-PET. Amyloid-PET levels did not differ between KL-VShet carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VShet against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.

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Challenging the Conclusion That Lower Preinduction Cognitive Ability Increases Risk for Combat-Related Post-Traumatic Stress Disorder in 2,375 Combat-Exposed, Vietnam War Veterans

Military Medicine ◽

10.7205/milmed.173.6.576 ◽

2008 ◽

Vol 173 (6) ◽

pp. 576-582 ◽

Cited By ~ 15

Author(s):

William W. Thompson ◽

Irving I. Gottesman

Keyword(s):

Cognitive Ability ◽

Vietnam War ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Post Traumatic Stress ◽

War Veterans ◽

Post Traumatic ◽

Vietnam War Veterans

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Plasma neurofilament light is associated with white matter damage in Alzheimer's disease

10.21203/rs.3.rs-115308/v2 ◽

2020 ◽

Author(s):

Fardin Nabizadeh ◽

Mohammad Balabandian ◽

Mohammad Reza Rostami ◽

Samuel Berchi Kankam ◽

Fetemeh Ranjbaran ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Diffusion Tensor ◽

Amyloid Β ◽

Brain Regions ◽

Csf Biomarkers ◽

Cross Sectional ◽

Neurofilament Light ◽

Microstructural Changes

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration, and synaptic damage in AD. However, few investigations have been carried out on the association between plasma NFL and white matter microstructure integrity. We have investigated the cross-sectional associations of plasma NFL, CSF total tau, phosphorylated tau, and Amyloid β with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, separately using a partial correlation model controlled for the effect of age, sex, and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL negatively correlates with FA and the positive correlation with RD, DA, and MD values in different regions. Our findings showed that plasma NFL is associated with white matter changes and AD-related features, including atrophy and hypometabolism. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and MCI progression to AD.

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