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2. Consensus Paper: Cerebellum and Ageing

Author

Arleo, Angelo, Bareš, Martin, Bernard, Jessica A., Bogoian, Hannah R., Bruchhage, Muriel M. K., Bryant, Patrick, Carlson, Erik S., Chan, Chetwyn C. H., Chen, Liang-Kung, Chung, Chih-Ping, Dotson, Vonetta M., Filip, Pavel, Guell, Xavier, Habas, Christophe, Jacobs, Heidi I.L., Kakei, Shinji, Lee, Tatia M. C., Leggio, Maria, Misiura, Maria, Mitoma, Hiroshi, Olivito, Giusy, Ramanoël, Stephen, Rezaee, Zeynab, Samstag, Colby L., Schmahmann, Jeremy D., Sekiyama, Kaoru, Wong, Clive H. Y., Yamashita, Masatoshi, and Manto, Mario

Published
2024
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7. Lower Locus Coeruleus Integrity Signals Elevated Entorhinal Tau and Clinical Progression in Asymptomatic Older Individuals.

Author

Engels‐Domínguez, Nina, Riphagen, Joost M., Van Egroo, Maxime, Koops, Elouise A., Smegal, Lindsay F., Becker, J. Alex, Prokopiou, Prokopis C., Bueichekú, Elisenda, Kwong, Kenneth K., Rentz, Dorene M., Salat, David H., Sperling, Reisa A., Johnson, Keith A., and Jacobs, Heidi I.L.

Subjects
LOCUS coeruleus, PROPORTIONAL hazards models, POSITRON emission tomography, MAGNETIC resonance imaging, RECEIVER operating characteristic curves
Abstract

Objective: Elevated entorhinal cortex (EC) tau in low beta‐amyloid individuals can predict accumulation of pathology and cognitive decline. We compared the accuracy of magnetic resonance imaging (MRI)‐derived locus coeruleus integrity, neocortical beta‐amyloid burden by positron emission tomography (PET), and hippocampal volume in identifying elevated entorhinal tau signal in asymptomatic individuals who are considered beta‐amyloid PET‐negative. Methods: We included 188 asymptomatic individuals (70.78 ± 11.51 years, 58% female) who underwent 3T‐MRI of the locus coeruleus, Pittsburgh compound‐B (PiB), and Flortaucipir (FTP) PET. Associations between elevated EC tau and neocortical PiB, hippocampal volume, or locus coeruleus integrity were evaluated and compared using logistic regression and receiver operating characteristic analyses in the PiB− sample with a clinical dementia rating (CDR) of 0. Associations with clinical progression (CDR‐sum‐of‐boxes) over a time span of 6 years were evaluated with Cox proportional hazard models. Results: We identified 26 (21%) individuals with high EC FTP in the CDR = 0/PiB− sample. Locus coeruleus integrity was a significantly more sensitive and specific predictor of elevated EC FTP (area under the curve [AUC] = 85%) compared with PiB (AUC = 77%) or hippocampal volume (AUC = 76%). Based on the Youden‐index, locus coeruleus integrity obtained a sensitivity of 77% and 85% specificity. Using the resulting locus coeruleus Youden cut‐off, lower locus coeruleus integrity was associated with a two‐fold increase in clinical progression, including mild cognitive impairment. Interpretation: Locus coeruleus integrity has promise as a low‐cost, non‐invasive screening instrument to detect early cortical tau deposition and associated clinical progression in asymptomatic, low beta‐amyloid individuals. ANN NEUROL 2024;96:650–661 [ABSTRACT FROM AUTHOR]

Published
2024
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11. Defining and characterizing neocortical tau resistance in preclinical Alzheimer’s Disease

Author

Properzi, Michael J, primary, Townsend, Diana, additional, Klinger, Hannah M, additional, Boyle, Rory, additional, Coughlan, Gillian T, additional, Hanseeuw, Bernard J, additional, Amariglio, Rebecca E., additional, Rentz, Dorene M., additional, Jacobs, Heidi I.L., additional, Price, Julie C, additional, Chhatwal, Jasmeer P., additional, Schultz, Aaron P., additional, Hohman, Timothy J., additional, Donohue, Michael C., additional, Johnson, Keith A., additional, Sperling, Reisa A., additional, and Buckley, Rachel F., additional

Published
2023
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13. Covid‐19 may have a detrimental impact on sensorimotor function

Author

Goss, Monica, primary, Bernal, Rebecca, additional, Patel, Vibhuti N, additional, Li, Karl, additional, Garbarino, Valentina R., additional, Nair, Rejani R, additional, Snyder, Heather M, additional, de Erausquin, Gabriel A., additional, Ganguli, Mary, additional, Snitz, Beth E., additional, Girard, Timothy D., additional, Jacobs, Heidi I.L., additional, Hosseini, Akram A., additional, Ibrahim, Tamer, additional, Vahidy, Farhaan S, additional, Satizabal, Claudia L., additional, Himali, Jayandra Jung, additional, and Seshadri, Sudha, additional

Published
2023
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15. Investigating white matter hyperintensities in a multicenter COVID‐19 study using 7T MRI

Author

Li, Jinghang, primary, Liou, Jr‐Jiun, additional, Santini, Tales, additional, Alkateeb, Salem, additional, Adeyemi, Oluwatobi F, additional, de Erausquin, Gabriel A., additional, Garbarino, Valentina R., additional, Goss, Monica, additional, Habes, Mohamad, additional, Himali, Jayandra Jung, additional, Karmonik, Christof, additional, Li, Karl, additional, Masdeu, Joseph C., additional, Nair, Rejani R, additional, Patel, Vibhuti N, additional, Snitz, Beth E., additional, Aizenstein, Howard J, additional, Wu, Minjie, additional, Bowtell, Richard, additional, Penny, Gowland, additional, Roman, Gustavo C, additional, Ganguli, Mary, additional, Vahidy, Farhaan S, additional, Girard, Timothy D., additional, Jacobs, Heidi I.L., additional, Hosseini, Akram A., additional, Seshadri, Sudha, additional, and Ibrahim, Tamer, additional

Published
2023
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16. Preliminary neurocognitive finding from a multi‐site study investing long‐term neurological impact of COVID‐19 using ultra‐high field 7 Tesla MRI‐based neuroimaging

Author

Tannous, Jonika D, primary, Vahidy, Farhaan S, additional, Patira, Riddhi, additional, Luckey, Alison M., additional, Gonzales, Mitzi M., additional, Hosseini, Akram A., additional, Girard, Timothy D., additional, Ibrahim, Tamer, additional, Jacobs, Heidi I.L., additional, Roman, Gustavo C, additional, Masdeu, Joseph C., additional, Karmonik, Christof, additional, Li, Karl, additional, Garbarino, Valentina R., additional, Goss, Monica, additional, Nair, Rejani R, additional, Patel, Vibhuti N, additional, Snyder, Heather M, additional, de Erausquin, Gabriel A., additional, Ganguli, Mary, additional, Seshadri, Sudha, additional, and Snitz, Beth E., additional

Published
2023
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17. Spatiotemporal Assessment of Locus Coeruleus Integrity Predicting Cortical Tau and Cognition

Author

Bueichekú, Elisenda, primary, Diez, Ibai Palacio, additional, Kim, Chan‐Mi, additional, Becker, Alex, additional, Koops, Elouise A., additional, Kwong, Kenneth, additional, Papp, Kathryn V., additional, Salat, David H, additional, Bennett, David A. A, additional, Rentz, Dorene M., additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Sepulcre, Jorge, additional, and Jacobs, Heidi I.L., additional

Published
2023
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19. Hippocampal subfield volumes in COVID‐19: a preliminary multicenter study using 7T MRI

Author

Santini, Tales, primary, Alkateeb, Salem, additional, Liou, Jr‐Jiun, additional, Li, Jinghang, additional, Adeyemi, Oluwatobi F, additional, de Erausquin, Gabriel A., additional, Garbarino, Valentina R., additional, Goss, Monica, additional, Habes, Mohamad, additional, Himali, Jayandra Jung, additional, Karmonik, Christof, additional, Li, Karl, additional, Masdeu, Joseph C., additional, Nair, Rejani R, additional, Patel, Vibhuti N, additional, Snitz, Beth E., additional, Bowtell, Richard, additional, Penny, Gowland, additional, Roman, Gustavo C, additional, Ganguli, Mary, additional, Vahidy, Farhaan S, additional, Girard, Timothy D., additional, Jacobs, Heidi I.L., additional, Hosseini, Akram A., additional, Seshadri, Sudha, additional, and Ibrahim, Tamer, additional

Published
2023
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20. Lower LC activity during high arousal conditions is related to greater plasma P‐Tau217 concentration in older individuals

Author

Prokopiou, Prokopis C., primary, Van Egroo, Maxime, additional, Riphagen, Joost M., additional, Ashton, Nicholas J., additional, Janelidze, Shorena, additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Blennow, Kaj, additional, Hansson, Oskar, additional, Zetterberg, Henrik, additional, and Jacobs, Heidi I.L., additional

Published
2023
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24. Using 7T MRI to study hippocampal structures in Alzheimer’s disease and post‐SARS‐CoV2 infection

Author

Hosseini, Akram A., primary, Adeyemi, Oluwatobi F, additional, Bowtell, Richard, additional, Penny, Gowland, additional, Ibrahim, Tamer, additional, Liou, Jr‐Jiun, additional, Santini, Tales, additional, Li, Jinghang, additional, Alkateeb, Salem, additional, Habes, Mohamad, additional, Goss, Monica, additional, Vahidy, Farhaan S, additional, Jacobs, Heidi I.L., additional, Girard, Timothy D., additional, de Erausquin, Gabriel A., additional, Snyder, Heather M, additional, and Seshadri, Sudha, additional

Published
2023
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25. Disparities in Research Participation within a Multi‐Racial SARS‐CoV‐2 Cohort for Evaluation of Ultrahigh Field (7T) MRI and Clinical Precursors of Alzheimer’s Disease and Related Dementias

Author

Vahidy, Farhaan S, primary, Hosseini, Akram A., additional, Girard, Timothy D., additional, Ibrahim, Tamer, additional, Jacobs, Heidi I.L., additional, Roman, Gustavo C, additional, Masdeu, Joseph C., additional, Li, Karl, additional, Garbarino, Valentina R., additional, Goss, Monica, additional, Nair, Rejani R, additional, Patel, Vibhuti N, additional, Snyder, Heather M, additional, Tannous, Jonika D, additional, Snitz, Beth E., additional, Ganguli, Mary, additional, and Seshadri, Sudha, additional

Published
2023
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28. Examining the influence of changes in amyloid burden on both contemporaneous and subsequent cognitive decline: using a latent change score approach

Author

Klinger, Hannah M, primary, Healy, Brian, additional, Hanseeuw, Bernard J, additional, Jones, Rich, additional, Townsend, Diana, additional, Properzi, Michael J, additional, Farrell, Michelle E., additional, Papp, Kathryn V., additional, Chhatwal, Jasmeer P., additional, Yang, Hyun‐Sik, additional, Schultz, Aaron P., additional, Amariglio, Rebecca E., additional, Jacobs, Heidi I.L., additional, Price, Julie C, additional, Johnson, Keith A., additional, Rentz, Dorene M., additional, Sperling, Reisa A., additional, and Buckley, Rachel F., additional

Published
2023
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29. Sex hormone binding globulin and total testosterone levels are associated with in vivo tau burden differentially between the sexes: findings from the Framingham Study

Author

Buckley, Rachel F., primary, McGrath, Emer R, additional, Scott, Matthew R, additional, Coughlan, Gillian T, additional, Boyle, Rory, additional, Seto, Mabel, additional, Ghosh, Saptaparni, additional, Jacobs, Heidi I.L., additional, Satizabal, Claudia L., additional, Thibault, Emma G., additional, Vasan, Ramachandran S, additional, Murabito, Joanne M, additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Seshadri, Sudha, additional, Jasuja, Ravi, additional, Bhasin, Shalender, additional, and Beiser, Alexa S., additional

Published
2023
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30. Lower locus coeruleus integrity in older COVID‐19 survivors: initial findings from an international 7T MRI consortium

Author

Jacobs, Heidi I.L., primary, Ibrahim, Tamer, additional, Vahidy, Farhaan S, additional, Girard, Timothy D., additional, Hosseini, Akram A., additional, Alkateeb, Salem, additional, Bowtell, Richard, additional, Penny, Gowland, additional, Habes, Mohamad, additional, Karmonik, Christof, additional, Mougin, Olivier, additional, Roman, Gustavo C, additional, Masdeu, Joseph C., additional, Li, Karl, additional, Garbarino, Valentina R., additional, Goss, Monica, additional, Nair, Rejani R, additional, Patel, Vibhuti N, additional, Snyder, Heather M, additional, Tannous, Jonika D, additional, de Erausquin, Gabriel A., additional, Snitz, Beth E., additional, and Seshadri, Sudha, additional

Published
2023
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31. Estimating a clinically normal individual’s position along a preclinical Alzheimer’s disease continuum using cognitive and amyloid trajectories

Author

Townsend, Diana, primary, Properzi, Michael J, additional, Betthauser, Tobey J, additional, Klinger, Hannah M, additional, Boyle, Rory, additional, Coughlan, Gillian T, additional, Hanseeuw, Bernard J, additional, Yang, Hyun‐Sik, additional, Amariglio, Rebecca E., additional, Farrell, Michelle E., additional, Jacobs, Heidi I.L., additional, Shirzadi, Zahra, additional, Yau, Wai‐Ying Wendy, additional, Price, Julie C, additional, Chhatwal, Jasmeer P., additional, Rentz, Dorene M., additional, Johnson, Keith A., additional, Sperling, Reisa A., additional, Schultz, Aaron P., additional, and Buckley, Rachel F., additional

Published
2023
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33. Associations of 24‐Hour Rest‐Activity Rhythm Fragmentation, Cognitive Decline, and Postmortem Locus Coeruleus Hypopigmentation in Alzheimer's Disease.

Author

Van Egroo, Maxime, van Someren, Eus J.W., Grinberg, Lea T., Bennett, David A., and Jacobs, Heidi I.L.

Subjects
LOCUS coeruleus, ALZHEIMER'S disease, AUTOPSY, COGNITION disorders, HYPOPIGMENTATION, CEREBRAL amyloid angiopathy
Abstract

Objective: While studies suggested that locus coeruleus (LC) neurodegeneration contributes to sleep–wake dysregulation in Alzheimer's disease (AD), the association between LC integrity and circadian rest‐activity patterns remains unknown. Here, we investigated the relationships between 24‐hour rest‐activity rhythms, cognitive trajectories, and autopsy‐derived LC integrity in older adults with and without cortical AD neuropathology. Methods: This retrospective study leveraged multi‐modal data from participants of the longitudinal clinical‐pathological Rush Memory and Aging Project. Indices of 24‐hour rest‐activity rhythm fragmentation (intradaily variability) and stability (interdaily stability) were extracted from annual actigraphic recordings, and cognitive trajectories were computed from annual cognitive evaluations. At autopsy, LC neurodegeneration was determined by the presence of hypopigmentation, and cortical AD neuropathology was assessed. Contributions of comorbid pathologies (Lewy bodies, cerebrovascular pathology) were evaluated. Results: Among the 388 cases included in the study sample (age at death = 92.1 ± 5.9 years; 273 women), 98 (25.3%) displayed LC hypopigmentation, and 251 (64.7%) exhibited cortical AD neuropathology. Logistic regression models showed that higher rest‐activity rhythm fragmentation, measured up to ~7.1 years before death, was associated with increased risk to display LC neurodegeneration at autopsy (odds ratio [OR] = 1.46, 95% confidence interval [CI95%]: 1.16–1.84, pBONF = 0.004), particularly in individuals with cortical AD neuropathology (OR = 1.56, CI95%: 1.15–2.15, pBONF = 0.03) and independently of comorbid pathologies. In addition, longitudinal increases in rest‐activity rhythm fragmentation partially mediated the association between LC neurodegeneration and cognitive decline (estimate = ‐0.011, CI95%: ‐0.023–‐0.002, pBONF = 0.03). Interpretation: These findings highlight the LC as a neurobiological correlate of sleep–wake dysregulation in AD, and further underscore the clinical relevance of monitoring rest‐activity patterns for improved detection of at‐risk individuals. ANN NEUROL 2024;95:653–664 [ABSTRACT FROM AUTHOR]

Published
2024
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34. Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease

Author

Prokopiou, Prokopis C., primary, Engels-Domínguez, Nina, additional, Schultz, Aaron P, additional, Sepulcre, Jorge, additional, Koops, Elouise A., additional, Papp, Kathryn V, additional, Marshall, Gad A., additional, Normandin, Marc D., additional, El Fakhri, Georges, additional, Rentz, Dorene, additional, Sperling, Reisa A., additional, Johnson, Keith A, additional, and Jacobs, Heidi I.L., additional

Published
2023
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35. Cognitive‐behavioral associations of amygdala subregional tau pathology in cognitively unimpaired Presenilin‐1 E280A mutation carriers

Author

Langella, Stephanie, primary, Sanchez, Justin S, additional, Martinez, Jairo E., additional, Rubinstein, Zoe B., additional, Baena, Ana Y., additional, Vila‐Castelar, Clara, additional, Ramirez‐Gomez, Liliana A., additional, Aduen, Paula, additional, Jacobs, Heidi I.L., additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Lopera, Francisco, additional, Gatchel, Jennifer R, additional, and Quiroz, Yakeel T., additional

Published
2022
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36. Plasma ptau231 predicts locus coeruleus integrity earlier in life than other Alzheimer’s disease plasma markers: a 7T MRI study across the adult lifespan

Author

Jacobs, Heidi I.L., primary, Riphagen, Joost M., additional, Ashton, Nicholas J., additional, Janelidze, Shorena, additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Yang, Hyun‐Sik, additional, Blennow, Kaj, additional, Hansson, Oskar, additional, Zetterberg, Henrik, additional, and Van Egroo, Maxime, additional

Published
2022
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37. Longitudinal hippocampal atrophy is associated with cognitive decline independently of amyloid and tau in neocortex

Author

Hanseeuw, Bernard, primary, Jacobs, Heidi I.L., additional, Schultz, Aaron P, additional, Buckley, Rachel F., additional, Properzi, Michael J, additional, Becker, Alex, additional, Farrell, Michelle E., additional, Sanchez, Justin S, additional, Papp, Kathryn V., additional, Yang, Hyun‐Sik, additional, Chhatwal, Jasmeer P., additional, Price, Julie C, additional, Fakhri, Georges El, additional, Rentz, Dorene M., additional, Sperling, Reisa A., additional, and Johnson, Keith A., additional

Published
2022
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38. Lower novelty‐related locus coeruleus function is associated with entorhinal tau‐mediated memory decline in older individuals.

Author

Prokopiou, Prokopis C., primary, Engels, Nina, additional, Schneider, Christoph, additional, Schultz, Aaron P., additional, Sepulcre, Jorge, additional, Riphagen, Joost M., additional, Koops, Elouise A., additional, Papp, Kathryn V., additional, Fakhri, Georges El, additional, Rentz, Dorene M., additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, and Jacobs, Heidi I.L., additional

Published
2022
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39. Developing early vulnerable area aggregates for PET detection of beta‐amyloid based on young and middle‐aged adults from the Framingham Heart Study

Author

Thibault, Emma G., primary, Farrell, Michelle E., additional, Beiser, Alexa S, additional, Becker, Alex, additional, Satizabal, Claudia L, additional, Jacobs, Heidi I.L., additional, DeCarli, Charles S., additional, Hanseeuw, Bernard, additional, Killiany, Ronald J, additional, Sperling, Reisa A., additional, Seshadri, Sudha, additional, and Johnson, Keith A., additional

Published
2022
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40. Associations Between Mild Behavioral Impairment (MBI‐C) Affective Domains and Alzheimer’s Disease Neuroimaging Biomarkers in Older Adults

Author

Mayblyum, Danielle V., primary, Quiroz, Yakeel T., additional, Langella, Stephanie, additional, Udeogu, Onyinye J., additional, Jacobs, Heidi I.L., additional, Rubinstein, Zoe B., additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Blacker, Deborah, additional, Marshall, Gad A, additional, and Gatchel, Jennifer R, additional

Published
2022
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42. Using 7T MRI to Evaluate COVID‐19 and Brain

Author

Hosseini, Akram A., primary, Bowtell, Richard, additional, Mougin, Olivier, additional, Penny, Gowland, additional, Katshu, Mohammad Zia, additional, Mukaetova‐Ladinska, Elizabeta, additional, Ibrahim, Tamer, additional, Girard, Timothy D., additional, Vahidy, Farhaan S., additional, Jacobs, Heidi I.L., additional, Snyder, Heather M., additional, de Erausquin, Gabriel A., additional, and Seshadri, Sudha, additional

Published
2022
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44. Vascular health is associated with locus coeruleus‐related entorhinal tau deposition

Author

Riphagen, Joost M., primary, Chhatwal, Jasmeer P., additional, Becker, Alex, additional, Kwong, Kenneth, additional, Engels, Nina, additional, Yau, Wai‐Ying Wendy, additional, Prokopiou, Prokopis C., additional, Schneider, Christoph, additional, Koops, Elouise A., additional, Rentz, Dorene M., additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, and Jacobs, Heidi I.L., additional

Published
2022
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46. Lower in‐vivo locus coeruleus integrity is associated with lower cortical thickness in older individuals with elevated Alzheimer’s pathology

Author

Engels, Nina, primary, Hsieh, Stephanie, additional, Schneider, Christoph, additional, Prokopiou, Prokopis C., additional, Schultz, Aaron P., additional, Riphagen, Joost M., additional, Koops, Elouise A., additional, Hanseeuw, Bernard, additional, Rentz, Dorene M., additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, and Jacobs, Heidi I.L., additional

Published
2022
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49. Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study

Author

Buckley, Rachel F., primary, O'Donnell, Adrienne, additional, McGrath, Emer R., additional, Jacobs, Heidi I.L., additional, Lois, Cristina, additional, Satizabal, Claudia L., additional, Ghosh, Saptaparni, additional, Rubinstein, Zoe B., additional, Murabito, Joanne M., additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Seshadri, Sudha, additional, and Beiser, Alexandra S., additional

Published
2022
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50. Locus coeruleus microstructural integrity is linked to plasma GFAP concentration and Aβ42/40 ratio in cognitively unimpaired individuals: a 7T MRI study.

Author

Patsyuk, Yuliya, Van Egroo, Maxime, van Hooren, Roy W.E., Ashton, Nicholas J., Blennow, Kaj, Zetterberg, Henrik, Poser, Benedikt A, and Jacobs, Heidi I.L.

Abstract

Background: Recent autopsy and in vivo MRI studies supported structural integrity of the brainstem locus coeruleus (LC) as a potential indicator of initial AD‐related pathological processes. Importantly, in the earliest stages of the disease, these changes to the neuronal density of the LC are associated with changes to the somatic morphology and dendritic atrophy. Here, we aimed to examine whether LC microstructural integrity, assessed in vivo with advanced diffusion‐weighted magnetic resonance imaging (dMRI), is related to plasma AD biomarkers in a sample of cognitively unimpaired individuals. Method: Fifty‐seven cognitively unimpaired participants (mean age = 59.3±14.7y; 28 females) (Table 1) underwent a dMRI scanning session using a multi‐shell, high angular resolution acquisition protocol in a 7T scanner. LC microstructure was evaluated by applying the Neurite Orientation Dispersion and Density Imaging (NODDI) biophysical model on the dMRI data, yielding two metrics of microstructural integrity: Neurite Density Index (NDI) and Orientation Dispersion Index (ODI). Additionally, blood samples were analyzed to assess AD plasma biomarkers, including Aβ42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau phosphorylated at threonine 181 (pTau181) or threonine 231 (pTau231). Result: Higher age was associated with lower LC ODI (t = ‐2.77, p = 0.008) but not LC NDI values (t = 0.44, p = 0.658). Multiple linear regressions adjusted for age, sex, and estimated Total Intracranial Volume (eTIV) showed that lower NDI in the LC was associated with higher plasma GFAP levels (t = ‐2.08, p =.04, Figure 1). In addition, we found a negative association between ODI within the LC and Aβ42/40 (t = ‐2.79, p =.007, Figure 2). No significant relationships were found between LC NDI/ODI values and plasma NfL or pTau biomarkers. Conclusion: Consistent with animal studies, these findings suggest that microstructural changes in the LC are associated with astroglial activation in the earliest stages of the disease. Associations with Aβ42/40 were unexpected but might reflect loss of white matter compartments or changes in lipid density. In future analyses, we will further examine the biological interpretation of the NODDI metrics in subcortical regions, in particular in the context of AD‐related processes. [ABSTRACT FROM AUTHOR]

Published
2023
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