Association of Cognitive Impairment With Free Water in the Nucleus Basalis of Meynert and Locus Coeruleus to Transentorhinal Cortex Tract.

Chu, Winston Thomas; Wang, Wei-En; Zaborszky, Laszlo; Golde, Todd Eliot; DeKosky, Steven; Duara, Ranjan; Loewenstein, David A; Adjouadi, Malek; Coombes, Stephen A; Vaillancourt, David E

Chu, Winston Thomas; Wang, Wei-En; Zaborszky, Laszlo; Golde, Todd Eliot; DeKosky, Steven; Duara, Ranjan; Loewenstein, David A; Adjouadi, Malek; Coombes, Stephen A; Vaillancourt, David E.

Affiliation

Chu WT; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Wang WE; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Zaborszky L; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Golde TE; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
DeKosky S; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Duara R; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Loewenstein DA; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Adjouadi M; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Coombes SA; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne
Vaillancourt DE; From the J. Crayton Pruitt Family Department of Biomedical Engineering (W.T.C., D.E.V.), Department of Applied Physiology and Kinesiology (W.T.C., W.-e.W., S.A.C., D.E.V.), Department of Neuroscience (T.E.G.); Center for Translational Research in Neurodegenerative Diseases (T.E.G.), Department of Ne

Neurology ; 98(7): e700-e710, 2022 02 15.

Article in En | MEDLINE | ID: mdl-34906980

ABSTRACT

ABSTRACT

BACKGROUND AND

OBJECTIVES:

The goal of this work was to determine the relationship between diffusion microstructure and early changes in Alzheimer disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain.

METHODS:

Diffusion MRI scans were collected on cognitively normal participants (CN) and patients with early mild cognitive impairment (EMCI), late mild cognitive impairment, and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, 4 magnocellular regions of the basal forebrain (e.g., nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples.

RESULTS:

FW was significantly higher in patients with EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen d = 0.54; p fdr < 0.05). FW was significantly higher in those with AD compared to CN in all the examined regions (mean Cohen d = 1.41; p fdr < 0.01). In addition, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all 5 cognitive impairment metrics and neurofilament light chain levels (mean r 2 = 0.10; p fdr < 0.05).

DISCUSSION:

These results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and noninvasive early marker of structural changes related to cognitive impairment.

Subject(s)

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease / Cognitive Dysfunction / Basal Forebrain Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Neurology Year: 2022 Document type: Article

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