The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort

Alexandra Touroutoglou; Yuta Katsumi; Michael Brickhouse; Alexander Zaitsev; Ryan Eckbo; Paul Aisen; Laurel Beckett; Jeffrey L. Dage; Ani Eloyan; Tatiana Foroud; Bernardino Ghetti; Percy Griffin; Dustin Hammers; Clifford R. Jack; Joel H. Kramer; Leonardo Iaccarino; Renaud La Joie; Nidhi S. Mundada; Robert Koeppe; Walter A. Kukull; Melissa E. Murray; Kelly Nudelman; Angelina J. Polsinelli; Malia Rumbaugh; David N. Soleimani-Meigooni; Arthur Toga; Prashanthi Vemuri; Alireza Atri; Gregory S. Day; Ranjan Duara; Neill R. Graff-Radford; Lawrence S. Honig; David T. Jones; Joseph C. Masdeu; Mario F. Mendez; Erik Musiek; Chiadi U. Onyike; Meghan Riddle; Emily Rogalski; Stephen Salloway; Sharon Sha; R. Scott Turner; Thomas S. Wingo; David A. Wolk; Kyle Womack; Maria C. Carrillo; Gil D. Rabinovici; Liana G. Apostolova; Bradford C. Dickerson

doi:10.1002/alz.13466

The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort

Alexandra Touroutoglou, Yuta Katsumi, Michael Brickhouse, Alexander Zaitsev, Ryan Eckbo, Paul Aisen, Laurel Beckett, Jeffrey L. Dage, Ani Eloyan, Tatiana Foroud, Bernardino Ghetti, Percy Griffin, Dustin Hammers, Clifford R. Jack, Joel H. Kramer, Leonardo Iaccarino, Renaud La Joie, Nidhi S. Mundada, Robert Koeppe, Walter A. KukullMelissa E. Murray, Kelly Nudelman, Angelina J. Polsinelli, Malia Rumbaugh, David N. Soleimani-Meigooni, Arthur Toga, Prashanthi Vemuri, Alireza Atri, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Lawrence S. Honig, David T. Jones, Joseph C. Masdeu, Mario F. Mendez, Erik Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, Stephen Salloway, Sharon Sha, R. Scott Turner, Thomas S. Wingo, David A. Wolk, Kyle Womack, Maria C. Carrillo, Gil D. Rabinovici, Liana G. Apostolova, Bradford C. Dickerson

Research output: Contribution to journal › Review article › peer-review

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.

Original language	English (US)
Pages (from-to)	S74-S88
Journal	Alzheimer's and Dementia
Volume	19
Issue number	S9
DOIs	https://doi.org/10.1002/alz.13466
State	Published - Nov 2023

Keywords

disease signature
early-onset Alzheimer's disease
magnetic resonance imaging (MRI)

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.13466

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Touroutoglou, A., Katsumi, Y., Brickhouse, M., Zaitsev, A., Eckbo, R., Aisen, P., Beckett, L., Dage, J. L., Eloyan, A., Foroud, T., Ghetti, B., Griffin, P., Hammers, D., Jack, C. R., Kramer, J. H., Iaccarino, L., Joie, R. L., Mundada, N. S., Koeppe, R., ... Dickerson, B. C. (2023). The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort. Alzheimer's and Dementia, 19(S9), S74-S88. https://doi.org/10.1002/alz.13466

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 et al.
In: Alzheimer's and Dementia, Vol. 19, No. S9, 11.2023, p. S74-S88.

Research output: Contribution to journal › Review article › peer-review

Touroutoglou, A, Katsumi, Y, Brickhouse, M, Zaitsev, A, Eckbo, R, Aisen, P, Beckett, L, Dage, JL, Eloyan, A, Foroud, T, Ghetti, B, Griffin, P, Hammers, D, Jack, CR, Kramer, JH, Iaccarino, L, Joie, RL, Mundada, NS, Koeppe, R, Kukull, WA, Murray, ME, Nudelman, K, Polsinelli, AJ, Rumbaugh, M, Soleimani-Meigooni, DN, Toga, A, Vemuri, P, Atri, A, Day, GS, Duara, R, Graff-Radford, NR, Honig, LS, Jones, DT, Masdeu, JC, Mendez, MF, Musiek, E, Onyike, CU, Riddle, M, Rogalski, E, Salloway, S, Sha, S, Turner, RS, Wingo, TS, Wolk, DA, Womack, K, Carrillo, MC, Rabinovici, GD, Apostolova, LG & Dickerson, BC 2023, 'The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort', Alzheimer's and Dementia, vol. 19, no. S9, pp. S74-S88. https://doi.org/10.1002/alz.13466

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title = "The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort",

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.",

keywords = "disease signature, early-onset Alzheimer's disease, magnetic resonance imaging (MRI)",

author = "Alexandra Touroutoglou and Yuta Katsumi and Michael Brickhouse and Alexander Zaitsev and Ryan Eckbo and Paul Aisen and Laurel Beckett and Dage, {Jeffrey L.} and Ani Eloyan and Tatiana Foroud and Bernardino Ghetti and Percy Griffin and Dustin Hammers and Jack, {Clifford R.} and Kramer, {Joel H.} and Leonardo Iaccarino and Joie, {Renaud La} and Mundada, {Nidhi S.} and Robert Koeppe and Kukull, {Walter A.} and Murray, {Melissa E.} and Kelly Nudelman and Polsinelli, {Angelina J.} and Malia Rumbaugh and Soleimani-Meigooni, {David N.} and Arthur Toga and Prashanthi Vemuri and Alireza Atri and Day, {Gregory S.} and Ranjan Duara and Graff-Radford, {Neill R.} and Honig, {Lawrence S.} and Jones, {David T.} and Masdeu, {Joseph C.} and Mendez, {Mario F.} and Erik Musiek and Onyike, {Chiadi U.} and Meghan Riddle and Emily Rogalski and Stephen Salloway and Sharon Sha and Turner, {R. Scott} and Wingo, {Thomas S.} and Wolk, {David A.} and Kyle Womack and Carrillo, {Maria C.} and Rabinovici, {Gil D.} and Apostolova, {Liana G.} and Dickerson, {Bradford C.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = nov,

doi = "10.1002/alz.13466",

language = "English (US)",

volume = "19",

pages = "S74--S88",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "S9",

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TY - JOUR

T1 - The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy

T2 - Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort

AU - Touroutoglou, Alexandra

AU - Katsumi, Yuta

AU - Brickhouse, Michael

AU - Zaitsev, Alexander

AU - Eckbo, Ryan

AU - Aisen, Paul

AU - Beckett, Laurel

AU - Dage, Jeffrey L.

AU - Eloyan, Ani

AU - Foroud, Tatiana

AU - Ghetti, Bernardino

AU - Griffin, Percy

AU - Hammers, Dustin

AU - Jack, Clifford R.

AU - Kramer, Joel H.

AU - Iaccarino, Leonardo

AU - Joie, Renaud La

AU - Mundada, Nidhi S.

AU - Koeppe, Robert

AU - Kukull, Walter A.

AU - Murray, Melissa E.

AU - Nudelman, Kelly

AU - Polsinelli, Angelina J.

AU - Rumbaugh, Malia

AU - Soleimani-Meigooni, David N.

AU - Toga, Arthur

AU - Vemuri, Prashanthi

AU - Atri, Alireza

AU - Day, Gregory S.

AU - Duara, Ranjan

AU - Graff-Radford, Neill R.

AU - Honig, Lawrence S.

AU - Jones, David T.

AU - Masdeu, Joseph C.

AU - Mendez, Mario F.

AU - Musiek, Erik

AU - Onyike, Chiadi U.

AU - Riddle, Meghan

AU - Rogalski, Emily

AU - Salloway, Stephen

AU - Sha, Sharon

AU - Turner, R. Scott

AU - Wingo, Thomas S.

AU - Wolk, David A.

AU - Womack, Kyle

AU - Carrillo, Maria C.

AU - Rabinovici, Gil D.

AU - Apostolova, Liana G.

AU - Dickerson, Bradford C.

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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.

KW - disease signature

KW - early-onset Alzheimer's disease

KW - magnetic resonance imaging (MRI)

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UR - http://www.scopus.com/inward/citedby.url?scp=85174256317&partnerID=8YFLogxK

U2 - 10.1002/alz.13466

DO - 10.1002/alz.13466

M3 - Review article

C2 - 37850549

AN - SCOPUS:85174256317

SN - 1552-5260

VL - 19

SP - S74-S88

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - S9

ER -

The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort

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