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Article ; Online: Subjective Cognition is Related to Patient-Reported Symptom Distress and Work Productivity Among Liver Transplant Recipients.

Ko, Dami / Ridner, Sheila H / Gifford, Katherine A

Transplant international : official journal of the European Society for Organ Transplantation

2023 Volume 36, Page(s) 10863

Abstract: Cognitive decline may prevent liver transplant (LT) recipients from staying healthy and independent. This study examined associations of objective and subjective, rated by LT recipients and caregivers, cognitive decline with patient-reported physical and ...

Abstract	Cognitive decline may prevent liver transplant (LT) recipients from staying healthy and independent. This study examined associations of objective and subjective, rated by LT recipients and caregivers, cognitive decline with patient-reported physical and psychological symptom distress, ability to perform household tasks, and workplace productivity among LT recipients. Sixty pairs of LT recipients and caregivers participated in this cross-sectional study. Subjective cognition was measured by the Everyday Cognition. Objective cognition was assessed with four cognitive tests, including the Repeatable Battery for the Assessment of Neuropsychological Status. Patient-reported outcomes were assessed with the Rotterdam Symptom Checklist-Modified, Profile of Mood States-Short Form, Creative Therapy Consultants Homemaking Assessment, and Work Limitations Questionnaire. Linear regression analyses related objective and subjective cognition to the patient-reported outcomes. While objective cognitive decline was not associated with any patient-reported outcomes, subjective cognitive decline was significantly associated with the outcomes. Higher LT recipient self-rated cognitive decline was associated with higher physical symptom distress (
MeSH term(s)	Humans ; Cross-Sectional Studies ; Liver Transplantation ; Cognition ; Cognitive Dysfunction/psychology ; Neuropsychological Tests
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.3389/ti.2023.10863
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Article ; Online: Subjective Cognition Reported by Caregivers Is Correlated With Objective Cognition in Liver Transplant Recipients.

Ko, Dami / Dietrich, Mary S / Gifford, Katherine A / Ridner, Sheila H

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

2021 Volume 28, Issue 2, Page(s) 269–279

Abstract: Objective cognitive assessments, a gold standard diagnostic tool for cognitive impairment, may not be feasible in busy liver transplantation (LT) practice because they are often time consuming. This study determined whether subjective cognition, patients' ...

Abstract	Objective cognitive assessments, a gold standard diagnostic tool for cognitive impairment, may not be feasible in busy liver transplantation (LT) practice because they are often time consuming. This study determined whether subjective cognition, patients' self-ratings and/or caregivers' ratings of patients' cognition, reflects objective cognition in LT recipients. A convenience sample of 60 adult LT recipients and their caregivers, recruited at a single transplant center, participated in this cross-sectional descriptive study. Subjective cognition (ie, recipient self-rated and caregiver rated) was measured using the Everyday Cognition (ECog; global and 6 domain scores). Objective global and domain-specific cognition of recipients was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Trail Making Test parts A and B, Digit Span Backward, and Rey-Osterrieth Complex Figure. Agreement between LT recipients' ECog scores and those of their caregivers was fair to moderate (intraclass correlation coefficient = 0.48 for global score, 0.35-0.56 for domain scores). Significant, albeit rather weak, correlations were found between subjective and objective scores. Recipients' ECog visuospatial abilities scores were correlated with Rey-Osterrieth Complex Figure scores (r
MeSH term(s)	Adult ; Caregivers/psychology ; Cognition ; Cross-Sectional Studies ; Humans ; Liver Transplantation/adverse effects ; Liver Transplantation/psychology ; Neuropsychological Tests
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2006866-9
ISSN	1527-6473 ; 1527-6465
ISSN (online)	1527-6473
ISSN	1527-6465
DOI	10.1002/lt.26213
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Article ; Online: Perivascular space burden interacts with APOE-ε4 status on cognition in older adults.

Gogniat, Marissa A / Khan, Omair A / Bown, Corey W / Liu, Dandan / Pechman, Kimberly R / Taylor Davis, L / Gifford, Katherine A / Landman, Bennett A / Hohman, Timothy J / Jefferson, Angela L

Neurobiology of aging

2024 Volume 136, Page(s) 1–8

Abstract: Enlarged perivascular spaces (ePVS) may adversely affect cognition. Little is known about how basal ganglia ePVS interact with apolipoprotein (APOE)-ε4 status. Vanderbilt Memory and Aging Project participants (n = 326, 73 ± 7, 59% male) underwent 3 T ... ...

Abstract	Enlarged perivascular spaces (ePVS) may adversely affect cognition. Little is known about how basal ganglia ePVS interact with apolipoprotein (APOE)-ε4 status. Vanderbilt Memory and Aging Project participants (n = 326, 73 ± 7, 59% male) underwent 3 T brain MRI at baseline to assess ePVS and longitudinal neuropsychological assessments. The interaction between ePVS volume and APOE-ε4 carrier status was related to baseline outcomes using ordinary least squares regressions and longitudinal cognition using linear mixed-effects regressions. ePVS volume interacted with APOE-ε4 status on cross-sectional naming performance (β = -0.002, p = 0.002), and executive function excluding outliers (β = 0.001, p = 0.009). There were no significant longitudinal interactions (p-values>0.10) except for Coding excluding outliers (β = 0.002, p = 0.05). While cross-sectional models stratified by APOE-ε4 status indicated greater ePVS related to worse cognition mostly in APOE-ε4 carriers, longitudinal models stratified by APOE-ε4 status showed greater ePVS volume related to worse cognition among APOE-ε4 non-carriers only. Results indicated that greater ePVS volume interacts with APOE-ε4 status on cognition cross-sectionally. Longitudinally, the association of greater ePVS volume and worse cognition appears stronger in APOE-ε4 non-carriers, possibly due to the deleterious effects of APOE-ε4 on cognition across the lifespan.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Apolipoprotein E4/genetics ; Cognition ; Cross-Sectional Studies ; Genotype ; Neuropsychological Tests ; Aged, 80 and over
Chemical Substances	Apolipoprotein E4
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2024.01.002
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Article ; Online: Biological correlates of elevated soluble TREM2 in cerebrospinal fluid.

Winfree, Rebecca L / Dumitrescu, Logan / Blennow, Kaj / Zetterberg, Henrik / Gifford, Katherine A / Pechman, Kimberly R / Jefferson, Angela L / Hohman, Timothy J

Neurobiology of aging

2022 Volume 118, Page(s) 88–98

Abstract: Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells-2 (sTREM2) is an emerging biomarker of neuroinflammation in Alzheimer's disease (AD). Yet, sTREM2 expression has not been systematically evaluated in relation to concomitant ...

Abstract	Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells-2 (sTREM2) is an emerging biomarker of neuroinflammation in Alzheimer's disease (AD). Yet, sTREM2 expression has not been systematically evaluated in relation to concomitant drivers of neuroinflammation. While associations between sTREM2 and tau in CSF are established, we sought to determine additional biological correlates of CSF sTREM2 during the prodromal stages of AD by evaluating CSF Aβ species (Aβ
MeSH term(s)	Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Humans ; Membrane Glycoproteins ; Receptors, Immunologic ; Serum Albumin ; tau Proteins/cerebrospinal fluid
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Membrane Glycoproteins ; Receptors, Immunologic ; Serum Albumin ; TREM2 protein, human ; tau Proteins
Language	English
Publishing date	2022-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2022.06.013
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Article: A deep neural network estimation of brain age is sensitive to cognitive impairment and decline.

Yang, Yisu / Sathe, Aditi / Schilling, Kurt / Shashikumar, Niranjana / Moore, Elizabeth / Dumitrescu, Logan / Pechman, Kimberly R / Landman, Bennett A / Gifford, Katherine A / Hohman, Timothy J / Jefferson, Angela L / Archer, Derek B

bioRxiv : the preprint server for biology

2023

Abstract: The greatest known risk factor for Alzheimer's disease (AD) is age. While both normal aging and AD pathology involve structural changes in the brain, their trajectories of atrophy are not the same. Recent developments in artificial intelligence have ... ...

Abstract	The greatest known risk factor for Alzheimer's disease (AD) is age. While both normal aging and AD pathology involve structural changes in the brain, their trajectories of atrophy are not the same. Recent developments in artificial intelligence have encouraged studies to leverage neuroimaging-derived measures and deep learning approaches to predict brain age, which has shown promise as a sensitive biomarker in diagnosing and monitoring AD. However, prior efforts primarily involved structural magnetic resonance imaging and conventional diffusion MRI (dMRI) metrics without accounting for partial volume effects. To address this issue, we post-processed our dMRI scans with an advanced free-water (FW) correction technique to compute distinct FW-corrected fractional anisotropy (FA
Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.10.552494
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Article ; Online: Baseline grey matter volumes and white matter hyperintensities predict decline in functional activities in older adults over a 5-year follow-up period.

Bolton, Corey J / Khan, Omair A / Moore, Elizabeth E / Pechman, Kimberly R / Taylor Davis, L / Liu, Dandan / Landman, Bennett A / Gifford, Katherine A / Hohman, Timothy J / Jefferson, Angela L

NeuroImage. Clinical

2023 Volume 38, Page(s) 103393

Abstract: Introduction: Functional independence is an essential predictor of quality of life in aging, yet few accessible predictors of functional decline have been identified. This study examined associations between baseline structural neuroimaging markers and ... ...

Abstract	Introduction: Functional independence is an essential predictor of quality of life in aging, yet few accessible predictors of functional decline have been identified. This study examined associations between baseline structural neuroimaging markers and longitudinal functional status. Methods: Linear mixed effects models with follow-up time interaction terms related baseline grey matter volume and white matter hyperintensities (WMHs) to functional trajectory, adjusting for demographic and medical covariates. Subsequent models assessed interactions with cognitive status and apolipoprotein E (APOE) ε4 status. Results: Smaller baseline grey matter volumes, particularly in regions commonly affected by Alzheimer's disease (AD), and greater baseline WMHs were associated with faster functional decline over a mean 5-year follow-up. Effects were stronger in APOE-ε4 carriers on grey matter variables. Cognitive status interacted with most MRI variables. Discussion: Greater atrophy in AD-related regions and higher WMH burden at study entry were associated with faster functional decline, particularly among participants at increased risk of AD.
MeSH term(s)	Humans ; Aged ; White Matter/diagnostic imaging ; Gray Matter/diagnostic imaging ; Follow-Up Studies ; Quality of Life ; Magnetic Resonance Imaging ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/psychology ; Apolipoprotein E4/genetics ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/psychology
Chemical Substances	Apolipoprotein E4
Language	English
Publishing date	2023-03-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2023.103393
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Article: Sex and Education Modify the Association Between Subjective Cognitive Decline and Amyloid Pathology.

Bolton, Corey J / Khan, Omair A / Liu, Dandan / Wilhoite, Sydney / Dumitrescu, Logan / Peterson, Amalia / Blennow, Kaj / Zetterberg, Henrik / Hohman, Timothy J / Jefferson, Angela L / Gifford, Katherine A

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Subjective cognitive decline (SCD) may be an early risk factor for dementia, particularly in highly educated individuals and women. This study examined the effect of education and sex on the association between SCD and Alzheimer's disease ( ... ...

Abstract	Background: Subjective cognitive decline (SCD) may be an early risk factor for dementia, particularly in highly educated individuals and women. This study examined the effect of education and sex on the association between SCD and Alzheimer's disease (AD) biomarkers in non-demented older adults. Method: Vanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=156, 72±6 years, 37% mild cognitive impairment, 33% female) completed fasting lumbar puncture, SCD assessment, and Wide Range Achievement Test-III Reading subtest to assess reading level at baseline as a a proxy for educational quality. Cerebrospinal fluid (CSF) biomarkers for AD (β-amyloid Result: In main effect models, higher SCD was associated with lower Aβ42 and Aβ42/40 ratio (p-values<0.004). SCD was not associated with tau, p-tau, or NfL levels ( Conclusion: Among community-dwelling older adults free of clinical dementia, higher SCD was associated with greater cerebral amyloid accumulation, one of the earliest pathological AD changes. SCD appears most useful in detecting early AD-related brain changes in men and individuals with higher quantity and quality of education. SCD was not associated with CSF markers of tau pathology or neurodegeneration. These findings suggest that considering sex and education is important when assessing SCD in older adults.
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.03.23297795
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Article: Clinical and demographic factors modify the association between plasma phosphorylated tau-181 and cognition.

Bolton, Corey J / Steinbach, Marilyn / Khan, Omair A / Liu, Dandan / O'Malley, Julia / Dumitrescu, Logan / Peterson, Amalia / Jefferson, Angela L / Hohman, Timothy J / Zetterberg, Henrik / Gifford, Katherine A

medRxiv : the preprint server for health sciences

2023

Abstract: Introduction: Plasma phosphorylated tau181 (p-tau181) associations with global cognition and memory are clear, but the link between p-tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimer's ... ...

Abstract	Introduction: Plasma phosphorylated tau181 (p-tau181) associations with global cognition and memory are clear, but the link between p-tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimer's disease (AD) and how this association changes based on genetic and demographic factors is poorly understood. Methods: Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and included 1185 adults aged >55 years with plasma p-tau181 and neuropsychological test data. Linear regression models related plasma p-tau181 to neuropsychological composite and SCD scores with follow-up models examining plasma p-tau181 interactions with cognitive diagnosis, Results: Higher plasma p-tau181 was associated with worse memory, executive functioning, and language abilities, and greater informant-reported SCD. Visuospatial abilities and self-report SCD were not associated with plasma p-tau181. Associations were generally stronger in MCI or dementia, Discussion: Higher levels of plasma p-tau181 are associated with worse neuropsychological test performance across multiple cognitive domains; however, these associations vary based on disease stage, genetic risk status, age, and sex.
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.03.23298051
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Article ; Online: A deep neural network estimation of brain age is sensitive to cognitive impairment and decline.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing

2023 Volume 29, Page(s) 148–162

Abstract	The greatest known risk factor for Alzheimer's disease (AD) is age. While both normal aging and AD pathology involve structural changes in the brain, their trajectories of atrophy are not the same. Recent developments in artificial intelligence have encouraged studies to leverage neuroimaging-derived measures and deep learning approaches to predict brain age, which has shown promise as a sensitive biomarker in diagnosing and monitoring AD. However, prior efforts primarily involved structural magnetic resonance imaging and conventional diffusion MRI (dMRI) metrics without accounting for partial volume effects. To address this issue, we post-processed our dMRI scans with an advanced free-water (FW) correction technique to compute distinct FW-corrected fractional anisotropy (FAFWcorr) and FW maps that allow for the separation of tissue from fluid in a scan. We built 3 densely connected neural networks from FW-corrected dMRI, T1-weighted MRI, and combined FW+T1 features, respectively, to predict brain age. We then investigated the relationship of actual age and predicted brain ages with cognition. We found that all models accurately predicted actual age in cognitively unimpaired (CU) controls (FW: r=0.66, p=1.62x10-32; T1: r=0.61, p=1.45x10-26, FW+T1: r=0.77, p=6.48x10-50) and distinguished between CU and mild cognitive impairment participants (FW: p=0.006; T1: p=0.048; FW+T1: p=0.003), with FW+T1-derived age showing best performance. Additionally, all predicted brain age models were significantly associated with cross-sectional cognition (memory, FW: β=-1.094, p=6.32x10-7; T1: β=-1.331, p=6.52x10-7; FW+T1: β=-1.476, p=2.53x10-10; executive function, FW: β=-1.276, p=1.46x10-9; T1: β=-1.337, p=2.52x10-7; FW+T1: β=-1.850, p=3.85x10-17) and longitudinal cognition (memory, FW: β=-0.091, p=4.62x10-11; T1: β=-0.097, p=1.40x10-8; FW+T1: β=-0.101, p=1.35x10-11; executive function, FW: β=-0.125, p=1.20x10-10; T1: β=-0.163, p=4.25x10-12; FW+T1: β=-0.158, p=1.65x10-14). Our findings provide evidence that both T1-weighted MRI and dMRI measures improve brain age prediction and support predicted brain age as a sensitive biomarker of cognition and cognitive decline.
MeSH term(s)	Humans ; Artificial Intelligence ; Cross-Sectional Studies ; Computational Biology ; Brain/diagnostic imaging ; Alzheimer Disease/diagnostic imaging ; Cognitive Dysfunction/diagnostic imaging ; Magnetic Resonance Imaging ; Neural Networks, Computer ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-12-29
Publishing country	United States
Document type	Journal Article
ISSN	2335-6936
ISSN (online)	2335-6936
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Article ; Online: Establishing Quality Control Procedures for Large-Scale Plasma Proteomics Analyses.

Patterson, Khiry L / Arul, Albert B / Choi, Min Ji / Oliver, Nekesa C / Whitaker, Marsalas D / Bodrick, Angel C / Libby, Julia B / Hansen, Shania / Dumitrescu, Logan / Gifford, Katherine A / Jefferson, Angela L / Hohman, Timothy J / Robinson, Renã A S

Journal of the American Society for Mass Spectrometry

2023 Volume 34, Issue 6, Page(s) 1105–1116

Abstract: Proteomics research has been transformed due to high-throughput liquid chromatography (LC-MS/MS) tandem mass spectrometry instruments combined with highly sophisticated automated sample preparation and multiplexing workflows. However, scaling proteomics ... ...

Abstract	Proteomics research has been transformed due to high-throughput liquid chromatography (LC-MS/MS) tandem mass spectrometry instruments combined with highly sophisticated automated sample preparation and multiplexing workflows. However, scaling proteomics experiments to large sample cohorts (hundreds to thousands) requires thoughtful quality control (QC) protocols. Robust QC protocols can help with reproducibility, quantitative accuracy, and provide opportunities for more decisive troubleshooting. Our laboratory conducted a plasma proteomics study of a cohort of
MeSH term(s)	Humans ; Tandem Mass Spectrometry/methods ; Proteomics/methods ; Chromatography, Liquid/methods ; Reproducibility of Results ; Peptides/chemistry ; Quality Control
Chemical Substances	Peptides
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1021/jasms.3c00050
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