Citations 4
EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease
Paranhos, Thiago , Katsumi, Yuta , Brickhouse, Michael , Eloyan, Ani , Eckbo, Ryan, Zaitsev, Alexander, Du, Anna, Joie, Renaud La , Thangarajah, Maryanne, Taurone, Alex , Vemuri, Prashanthi , Jack, Clifford R. , Hammers, Dustin B , Aisen, Paul , Beckett, Laurel , Koeppe, Robert A. , Kukull, Walter A. , Toga, Arthur W. , Atri, Alireza , Clark, David , Day, Gregory S. , Duara, Ranjan , Graff‐Radford, Neill R. , Honig, Lawrence S. , Johnson, Erik C. B. , Jones, David T. , Masdeu, Joseph C , Mendez, Mario F. , Musiek, Erik , Onyike, Chiadi U. , Riddle, Meghan , Rogalskı, Emily , Salloway, Stephen , Sha, Sharon J. , Turner, Raymond Scott , Wingo, Thomas S , Wolk, David A. , Womack, Kyle , Carrillo, María C. , Rabinovici, Gil D. , Apostolova, Liana G. , Dickerson, Bradford Clark , Eldaief, Mark C. , Touroutoglou, Alexandra
Neurology | August 26, 2026 | Volume: 107 | Issue: 7 | Pages: No page available
Relationships of CSF biomarkers to cortical atrophy in early‐onset Alzheimer's disease
Touroutoglou, Alexandra, Katsumi, Yuta, Hensel, Jennifer, Schindler, Suzanne E., Ibanez, Laura, Brickhouse, Michael, Eloyan, Ani, Eckbo, Ryan, Zaitsev, Alexander, Joie, Renaud La, Thangarajah, Maryanne, Taurone, Alexander, Vemuri, Prashanthi, Jack, Clifford R., Hammers, Dustin B., Foroud, Tatiana, Aisen, P, Ls, Beckett, Koeppe, Robert, Kukull, Walter A., Toga, Arthur, ATRI, A, Db, Clark, Day, Gregory S., Duara, Ranjan, Graff‐Radford, Neill R., Grant, Ian M., Ls, Honig, Johnson, Erik C. B., Jones, David T., Masdeu, J C, Mf, Mendez, Musiek, Erik, Onyike, Chiadi U., Riddle, Meghan, Rogalski, Emily, Salloway, Stephen, Sha, Sharon, Turner, R. Scott, Wingo, Thomas S., D, Von Dem Wolk, Womack, Kyle, Carrillo, Maria C., Rabinovici, Gil D., Apostolova, L G, JL, Dage, Dickerson, Bradford C., Eldaief, Mark C., Joie, Renaud La , La Joie, Renaud , Touroutoglou, Alexandra , Katsumi, Yuta , Schindler, Suzanne E. , Ibanez, Laura , Brickhouse, Michael , Eloyan, Ani , Thangarajah, Maryanne, Vemuri, Prashanthi , Jack, Clifford R. , Hammers, Dustin B , Foroud, Tatiana , Aisen, Paul , Beckett, Laurel, Koeppe, Robert A. , Kukull, Walter A. , Toga, Arthur W. , Atri, Alireza, Clark, David, Day, Gregory S. , Duara, Ranjan , Graff‐Radford, Neill R. , Johnson, Erik C. B. , Jones, David T. , Musiek, Erik , Onyike, Chiadi U. , Riddle, Meghan , Salloway, Stephen , Sha, Sharon J. , Turner, R. Scott, Wingo, Thomas S , Wolk, David A. , Womack, Kyle , Carrillo, María C. , Rabinovici, Gil D. , Apostolova, Liana G. , Dickerson, Bradford Clark , Eldaief, Mark C.
Alzheimer's & Dementia | July 21, 2026 | Volume: 22 | Issue: 7 | Pages: No page available
Abstract INTRODUCTION Although cerebrospinal fluid (CSF) biomarkers reflect neurodegeneration in Alzheimer's disease (AD), it remains unclear whether these biomarkers track neurodegeneration in early‐onset Alzheimer's disease (EOAD). METHODS In 80 EOAD patients, we examined correlations between eight CSF biomarker levels and cortical thickness decreases within the EOAD cortical atrophy signature. Significant correlations were then entered into a multiple regression analysis. We also examined contributions of EOAD atrophy and CSF biomarkers to cognitive impairment. RESULTS The levels of four CSF biomarkers correlated to EOAD signature atrophy. Stepwise regression analyses revealed that CSF neurofilament light chain (NfL) levels best predicted EOAD signature atrophy. Multiple regression showed EOAD signature atrophy combined with CSF NfL levels explained more variance in cognitive impairment than either factor alone. DISCUSSION Within EOAD patients, CSF NfL levels relate to the magnitude of cortical atrophy, and a combination of EOAD signature atrophy and CSF NfL levels most robustly predict cognitive impairment.
Dissociable spatial topography of cortical atrophy in early‐onset and late‐onset Alzheimer's disease: A head‐to‐head comparison of the LEADS and ADNI cohorts
Katsumi, Yuta , Touroutoglou, Alexandra , Brickhouse, Michael , Eloyan, Ani , Eckbo, Ryan, Zaitsev, Alexander, Joie, Renaud La , Thangarajah, Maryanne, Taurone, Alexander, Jack, Clifford R. , Dage, Jeffrey L. , Hammers, Dustin B. , Newell, Kathy L. , Polsinelli, Angelina J. , Aisen, Paul, Reman, Rema, Kramer, Joel H. , Day, Gregory S. , Duara, Ranjan , Graff‐Radford, Neill R. , Grant, Ian , Masdeu, Joseph C. , Mendez, Mario F. , Onyike, Chiadi U. , Riddle, Meghan , Rogalskı, Emily , Salloway, Stephen , Sha, Sharon, Turner, Raymond Scott , Wingo, Thomas S. , Carrillo, María C. , Rabinovici, Gil D. , Apostolova, Liana G. , Jack, Clifford R , Day, Gregory S , La Joie, Renaud , Rabinovici, Gil D , Wingo, Thomas S , Dage, Jeffrey L , Lagarde, Julien , Schonhaut, Daniel R. , Vemuri, Prashanthi , Nudelman, Kelly , Foroud, Tatiana , Hammers, Dustin B , Ghetti, Bernardino , Murray, Melissa E. , Beckett, Laurel , Atri, Alireza , Duara, Ranjan , Honig, Lawrence S. , Johnson, Erik C. B. , Jones, David T. , Masdeu, Joseph C , Musiek, Erik , Sha, Sharon J. , Wolk, David A. , Womack, Kyle , Dickerson, Bradford Clark
Alzheimer's & Dementia | February 19, 2025 | Volume: 21 | Issue: 2 | Pages: No page available
Abstract INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized cohorts (LEADS and ADNI). METHODS We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early‐stage AD), along with cognitively unimpaired participants. RESULTS After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD. DISCUSSION Our findings point to the clinical utility of MRI‐based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.
The Sporadic Early‐onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) Cohort
Touroutoglou, Alexandra , Katsumi, Yuta , Brickhouse, Michael , Zaitsev, Alexander, Eckbo, Ryan, Aisen, Paul, Dage, Jeffrey L. , Eloyan, Ani , Ghetti, Bernardino , Griffin, Percy , Hammers, Dustin B. , Jack, Clifford R. , Kramer, Joel H. , Joie, Renaud La , Mundada, Nidhi S. , Kukull, Walter A. , Polsinelli, Angelina J. , Rumbaugh, Malia, Soleimani‐Meigooni, David N. , Toga, Arthur W. , Vemuri, Prashanthi , Day, Gregory S. , Duara, Ranjan , Graff‐Radford, Neill R. , Masdeu, Joseph C. , Mendez, Mario F. , Onyike, Chiadi U. , Riddle, Meghan , Rogalskı, Emily , Salloway, Stephen , Sha, Sharon, Turner, Raymond Scott , Wingo, Thomas S. , Carrillo, María C. , Rabinovici, Gil D. , Apostolova, Liana G. , Jack, Clifford R , Vemuri, Prashanthi , Day, Gregory S , La Joie, Renaud , Rabinovici, Gil D , Ghetti, Bernardino F , Wingo, Thomas S , Dage, Jeffrey L , Beckett, Laurel , Foroud, Tatiana , Hammers, Dustin B , Iaccarino, Leonardo , Koeppe, Robert A. , Murray, Melissa E. , Nudelman, Kelly , Atri, Alireza , Duara, Ranjan , Honig, Lawrence S. , Jones, David T. , Masdeu, Joseph C , Musiek, Erik , Sha, Sharon J. , Wolk, David A. , Womack, Kyle , Dickerson, Bradford Clark
Alzheimer's & Dementia | October 18, 2023 | Volume: 19 | Issue: S9 | Pages: No page available
Abstract INTRODUCTION Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early‐onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. METHODS We analyzed MRI scans to define the sporadic EOAD‐signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early‐onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. RESULTS The EOAD‐signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD‐signature atrophy was associated with the severity of cognitive impairment. DISCUSSION The EOAD‐signature atrophy is a reliable and clinically valid biomarker of AD‐related neurodegeneration that could be used in clinical trials for EOAD. Highlights We developed an early‐onset Alzheimer's disease (EOAD)–signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD‐signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.