Functional connectivity in autosomal dominant and late-onset Alzheimer disease

Jewell B. Thomas, Matthew R. Brier, Randall J. Bateman, Abraham Z. Snyder, Tammie L. Benzinger, Chengjie Xiong, Marcus Raichle, David M. Holtzman, Reisa A. Sperling, Richard Mayeux, Bernardino Ghetti, John M. Ringman, Stephen Salloway, Eric McDade, Martin N. Rossor, Sebastien Ourselin, Peter R. Schofield, Colin L. Masters, Ralph N. Martins, Michael W. Weiner & 18 others Paul M. Thompson, Nick C. Fox, Robert A. Koeppe, Clifford R. Jack, Chester A. Mathis, Angela Oliver, Tyler M. Blazey, Krista Moulder, Virginia Buckles, Russ Hornbeck, Jasmeer Chhatwal, Aaron P. Schultz, Alison M. Goate, Anne M. Fagan, Nigel J. Cairns, Daniel S. Marcus, John C. Morris, Beau M. Ances

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

IMPORTANCE: Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. OBJECTIVE: To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. DESIGN, SETTING, AND PARTICIPANTS: We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivitymagnetic resonance imaging at multiple international academic sites. MAIN OUTCOMES AND MEASURES: For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. RESULTS: A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. CONCLUSIONS AND RELEVANCE: Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivitymagnetic resonance imagingmay be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.

Original languageEnglish
Pages (from-to)1111-1122
Number of pages12
JournalJAMA Neurology
Volume71
Issue number9
DOIs
StatePublished - Sep 1 2014

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Alzheimer Disease
Dementia
Connectivity
Onset
Alzheimer's Disease
Mutation
Logistic Models
Age of Onset
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

Thomas, J. B., Brier, M. R., Bateman, R. J., Snyder, A. Z., Benzinger, T. L., Xiong, C., ... Ances, B. M. (2014). Functional connectivity in autosomal dominant and late-onset Alzheimer disease. JAMA Neurology, 71(9), 1111-1122. https://doi.org/10.1001/jamaneurol.2014.1654

Functional connectivity in autosomal dominant and late-onset Alzheimer disease. / Thomas, Jewell B.; Brier, Matthew R.; Bateman, Randall J.; Snyder, Abraham Z.; Benzinger, Tammie L.; Xiong, Chengjie; Raichle, Marcus; Holtzman, David M.; Sperling, Reisa A.; Mayeux, Richard; Ghetti, Bernardino; Ringman, John M.; Salloway, Stephen; McDade, Eric; Rossor, Martin N.; Ourselin, Sebastien; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Weiner, Michael W.; Thompson, Paul M.; Fox, Nick C.; Koeppe, Robert A.; Jack, Clifford R.; Mathis, Chester A.; Oliver, Angela; Blazey, Tyler M.; Moulder, Krista; Buckles, Virginia; Hornbeck, Russ; Chhatwal, Jasmeer; Schultz, Aaron P.; Goate, Alison M.; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; Morris, John C.; Ances, Beau M.

In: JAMA Neurology, Vol. 71, No. 9, 01.09.2014, p. 1111-1122.

Research output: Contribution to journalArticle

Thomas, JB, Brier, MR, Bateman, RJ, Snyder, AZ, Benzinger, TL, Xiong, C, Raichle, M, Holtzman, DM, Sperling, RA, Mayeux, R, Ghetti, B, Ringman, JM, Salloway, S, McDade, E, Rossor, MN, Ourselin, S, Schofield, PR, Masters, CL, Martins, RN, Weiner, MW, Thompson, PM, Fox, NC, Koeppe, RA, Jack, CR, Mathis, CA, Oliver, A, Blazey, TM, Moulder, K, Buckles, V, Hornbeck, R, Chhatwal, J, Schultz, AP, Goate, AM, Fagan, AM, Cairns, NJ, Marcus, DS, Morris, JC & Ances, BM 2014, 'Functional connectivity in autosomal dominant and late-onset Alzheimer disease', JAMA Neurology, vol. 71, no. 9, pp. 1111-1122. https://doi.org/10.1001/jamaneurol.2014.1654
Thomas JB, Brier MR, Bateman RJ, Snyder AZ, Benzinger TL, Xiong C et al. Functional connectivity in autosomal dominant and late-onset Alzheimer disease. JAMA Neurology. 2014 Sep 1;71(9):1111-1122. https://doi.org/10.1001/jamaneurol.2014.1654
Thomas, Jewell B. ; Brier, Matthew R. ; Bateman, Randall J. ; Snyder, Abraham Z. ; Benzinger, Tammie L. ; Xiong, Chengjie ; Raichle, Marcus ; Holtzman, David M. ; Sperling, Reisa A. ; Mayeux, Richard ; Ghetti, Bernardino ; Ringman, John M. ; Salloway, Stephen ; McDade, Eric ; Rossor, Martin N. ; Ourselin, Sebastien ; Schofield, Peter R. ; Masters, Colin L. ; Martins, Ralph N. ; Weiner, Michael W. ; Thompson, Paul M. ; Fox, Nick C. ; Koeppe, Robert A. ; Jack, Clifford R. ; Mathis, Chester A. ; Oliver, Angela ; Blazey, Tyler M. ; Moulder, Krista ; Buckles, Virginia ; Hornbeck, Russ ; Chhatwal, Jasmeer ; Schultz, Aaron P. ; Goate, Alison M. ; Fagan, Anne M. ; Cairns, Nigel J. ; Marcus, Daniel S. ; Morris, John C. ; Ances, Beau M. / Functional connectivity in autosomal dominant and late-onset Alzheimer disease. In: JAMA Neurology. 2014 ; Vol. 71, No. 9. pp. 1111-1122.
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abstract = "IMPORTANCE: Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. OBJECTIVE: To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. DESIGN, SETTING, AND PARTICIPANTS: We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivitymagnetic resonance imaging at multiple international academic sites. MAIN OUTCOMES AND MEASURES: For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. RESULTS: A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. CONCLUSIONS AND RELEVANCE: Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivitymagnetic resonance imagingmay be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.",
author = "Thomas, {Jewell B.} and Brier, {Matthew R.} and Bateman, {Randall J.} and Snyder, {Abraham Z.} and Benzinger, {Tammie L.} and Chengjie Xiong and Marcus Raichle and Holtzman, {David M.} and Sperling, {Reisa A.} and Richard Mayeux and Bernardino Ghetti and Ringman, {John M.} and Stephen Salloway and Eric McDade and Rossor, {Martin N.} and Sebastien Ourselin and Schofield, {Peter R.} and Masters, {Colin L.} and Martins, {Ralph N.} and Weiner, {Michael W.} and Thompson, {Paul M.} and Fox, {Nick C.} and Koeppe, {Robert A.} and Jack, {Clifford R.} and Mathis, {Chester A.} and Angela Oliver and Blazey, {Tyler M.} and Krista Moulder and Virginia Buckles and Russ Hornbeck and Jasmeer Chhatwal and Schultz, {Aaron P.} and Goate, {Alison M.} and Fagan, {Anne M.} and Cairns, {Nigel J.} and Marcus, {Daniel S.} and Morris, {John C.} and Ances, {Beau M.}",
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T1 - Functional connectivity in autosomal dominant and late-onset Alzheimer disease

AU - Thomas, Jewell B.

AU - Brier, Matthew R.

AU - Bateman, Randall J.

AU - Snyder, Abraham Z.

AU - Benzinger, Tammie L.

AU - Xiong, Chengjie

AU - Raichle, Marcus

AU - Holtzman, David M.

AU - Sperling, Reisa A.

AU - Mayeux, Richard

AU - Ghetti, Bernardino

AU - Ringman, John M.

AU - Salloway, Stephen

AU - McDade, Eric

AU - Rossor, Martin N.

AU - Ourselin, Sebastien

AU - Schofield, Peter R.

AU - Masters, Colin L.

AU - Martins, Ralph N.

AU - Weiner, Michael W.

AU - Thompson, Paul M.

AU - Fox, Nick C.

AU - Koeppe, Robert A.

AU - Jack, Clifford R.

AU - Mathis, Chester A.

AU - Oliver, Angela

AU - Blazey, Tyler M.

AU - Moulder, Krista

AU - Buckles, Virginia

AU - Hornbeck, Russ

AU - Chhatwal, Jasmeer

AU - Schultz, Aaron P.

AU - Goate, Alison M.

AU - Fagan, Anne M.

AU - Cairns, Nigel J.

AU - Marcus, Daniel S.

AU - Morris, John C.

AU - Ances, Beau M.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - IMPORTANCE: Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. OBJECTIVE: To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. DESIGN, SETTING, AND PARTICIPANTS: We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivitymagnetic resonance imaging at multiple international academic sites. MAIN OUTCOMES AND MEASURES: For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. RESULTS: A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. CONCLUSIONS AND RELEVANCE: Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivitymagnetic resonance imagingmay be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.

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