The pattern of atrophy in familial alzheimer disease: Volumetric MRI results from the DIAN study

David M. Cash, Gerard R. Ridgway, Yuying Liang, Natalie S. Ryan, Kirsi M. Kinnunen, Thomas Yeatman, Ian B. Malone, Tammie L S Benzinger, Clifford R. Jack, Paul M. Thompson, Bernardino Ghetti, Andrew Saykin, Colin L. Masters, John M. Ringman, Stephen P. Salloway, Peter R. Schofield, Reisa A. Sperling, Nigel J. Cairns, Daniel S. Marcus, Chengjie XiongRandall J. Bateman, John C. Morris, Martin N. Rossor, Sébastien Ourselin, Nick C. Fox

Research output: Contribution to journalArticle

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Abstract

Objective: To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers. Methods: A total of 192 participants with volumetric T1-weighted MRI, genotyping, and clinical diagnosis were available from the Dominantly Inherited Alzheimer Network. Of these, 69 were presymptomatic mutation carriers, 50 were symptomatic carriers (31 with Clinical Dementia Rating [CDR] = 0.5, 19 with CDR > 0.5), and 73 were noncarriers from the same families. Voxelbased morphometry was used to identify cross-sectional group differences in gray matter and white matter volume. Results: Significant differences in gray matter (p < 0.05, family-wise error-corrected) were observed between noncarriers and mildly symptomatic (CDR = 0.5) carriers in the thalamus and putamen, as well as in the temporal lobe, precuneus, and cingulate gyrus; the same pattern, but with more extensive changes, was seen in those with CDR > 0.5. Significant white matter differences between noncarriers and symptomatic carriers were observed in the cingulum and fornix; these form input and output connections to the medial temporal lobe, cingulate, and precuneus. No differences between noncarriers and presymptomatic carriers survived correction for multiple comparisons, but there was a trend for decreased gray matter in the thalamus for carriers closer to their estimated age at onset. There were no significant increases of gray or white matter in asymptomatic or symptomatic carriers compared to noncarriers. Conclusions: Atrophy in FAD is observed early, both in areas commonly associated with sporadic Alzheimer disease and also in the putamen and thalamus, 2 regions associated with early amyloid deposition in FAD mutation carriers.

Original languageEnglish
Pages (from-to)1425-1433
Number of pages9
JournalNeurology
Volume81
Issue number16
DOIs
StatePublished - Oct 15 2013

Fingerprint

Atrophy
Alzheimer Disease
Thalamus
Mutation
Dementia
Parietal Lobe
Putamen
Temporal Lobe
Age of Onset
Amyloid
Gray Matter
Familial
Alzheimer's Disease
Carrier
White Matter
Grey Matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Cash, D. M., Ridgway, G. R., Liang, Y., Ryan, N. S., Kinnunen, K. M., Yeatman, T., ... Fox, N. C. (2013). The pattern of atrophy in familial alzheimer disease: Volumetric MRI results from the DIAN study. Neurology, 81(16), 1425-1433. https://doi.org/10.1212/WNL.0b013e3182a841c6

The pattern of atrophy in familial alzheimer disease : Volumetric MRI results from the DIAN study. / Cash, David M.; Ridgway, Gerard R.; Liang, Yuying; Ryan, Natalie S.; Kinnunen, Kirsi M.; Yeatman, Thomas; Malone, Ian B.; Benzinger, Tammie L S; Jack, Clifford R.; Thompson, Paul M.; Ghetti, Bernardino; Saykin, Andrew; Masters, Colin L.; Ringman, John M.; Salloway, Stephen P.; Schofield, Peter R.; Sperling, Reisa A.; Cairns, Nigel J.; Marcus, Daniel S.; Xiong, Chengjie; Bateman, Randall J.; Morris, John C.; Rossor, Martin N.; Ourselin, Sébastien; Fox, Nick C.

In: Neurology, Vol. 81, No. 16, 15.10.2013, p. 1425-1433.

Research output: Contribution to journalArticle

Cash, DM, Ridgway, GR, Liang, Y, Ryan, NS, Kinnunen, KM, Yeatman, T, Malone, IB, Benzinger, TLS, Jack, CR, Thompson, PM, Ghetti, B, Saykin, A, Masters, CL, Ringman, JM, Salloway, SP, Schofield, PR, Sperling, RA, Cairns, NJ, Marcus, DS, Xiong, C, Bateman, RJ, Morris, JC, Rossor, MN, Ourselin, S & Fox, NC 2013, 'The pattern of atrophy in familial alzheimer disease: Volumetric MRI results from the DIAN study', Neurology, vol. 81, no. 16, pp. 1425-1433. https://doi.org/10.1212/WNL.0b013e3182a841c6
Cash DM, Ridgway GR, Liang Y, Ryan NS, Kinnunen KM, Yeatman T et al. The pattern of atrophy in familial alzheimer disease: Volumetric MRI results from the DIAN study. Neurology. 2013 Oct 15;81(16):1425-1433. https://doi.org/10.1212/WNL.0b013e3182a841c6
Cash, David M. ; Ridgway, Gerard R. ; Liang, Yuying ; Ryan, Natalie S. ; Kinnunen, Kirsi M. ; Yeatman, Thomas ; Malone, Ian B. ; Benzinger, Tammie L S ; Jack, Clifford R. ; Thompson, Paul M. ; Ghetti, Bernardino ; Saykin, Andrew ; Masters, Colin L. ; Ringman, John M. ; Salloway, Stephen P. ; Schofield, Peter R. ; Sperling, Reisa A. ; Cairns, Nigel J. ; Marcus, Daniel S. ; Xiong, Chengjie ; Bateman, Randall J. ; Morris, John C. ; Rossor, Martin N. ; Ourselin, Sébastien ; Fox, Nick C. / The pattern of atrophy in familial alzheimer disease : Volumetric MRI results from the DIAN study. In: Neurology. 2013 ; Vol. 81, No. 16. pp. 1425-1433.
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abstract = "Objective: To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers. Methods: A total of 192 participants with volumetric T1-weighted MRI, genotyping, and clinical diagnosis were available from the Dominantly Inherited Alzheimer Network. Of these, 69 were presymptomatic mutation carriers, 50 were symptomatic carriers (31 with Clinical Dementia Rating [CDR] = 0.5, 19 with CDR > 0.5), and 73 were noncarriers from the same families. Voxelbased morphometry was used to identify cross-sectional group differences in gray matter and white matter volume. Results: Significant differences in gray matter (p < 0.05, family-wise error-corrected) were observed between noncarriers and mildly symptomatic (CDR = 0.5) carriers in the thalamus and putamen, as well as in the temporal lobe, precuneus, and cingulate gyrus; the same pattern, but with more extensive changes, was seen in those with CDR > 0.5. Significant white matter differences between noncarriers and symptomatic carriers were observed in the cingulum and fornix; these form input and output connections to the medial temporal lobe, cingulate, and precuneus. No differences between noncarriers and presymptomatic carriers survived correction for multiple comparisons, but there was a trend for decreased gray matter in the thalamus for carriers closer to their estimated age at onset. There were no significant increases of gray or white matter in asymptomatic or symptomatic carriers compared to noncarriers. Conclusions: Atrophy in FAD is observed early, both in areas commonly associated with sporadic Alzheimer disease and also in the putamen and thalamus, 2 regions associated with early amyloid deposition in FAD mutation carriers.",
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T1 - The pattern of atrophy in familial alzheimer disease

T2 - Volumetric MRI results from the DIAN study

AU - Cash, David M.

AU - Ridgway, Gerard R.

AU - Liang, Yuying

AU - Ryan, Natalie S.

AU - Kinnunen, Kirsi M.

AU - Yeatman, Thomas

AU - Malone, Ian B.

AU - Benzinger, Tammie L S

AU - Jack, Clifford R.

AU - Thompson, Paul M.

AU - Ghetti, Bernardino

AU - Saykin, Andrew

AU - Masters, Colin L.

AU - Ringman, John M.

AU - Salloway, Stephen P.

AU - Schofield, Peter R.

AU - Sperling, Reisa A.

AU - Cairns, Nigel J.

AU - Marcus, Daniel S.

AU - Xiong, Chengjie

AU - Bateman, Randall J.

AU - Morris, John C.

AU - Rossor, Martin N.

AU - Ourselin, Sébastien

AU - Fox, Nick C.

PY - 2013/10/15

Y1 - 2013/10/15

N2 - Objective: To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers. Methods: A total of 192 participants with volumetric T1-weighted MRI, genotyping, and clinical diagnosis were available from the Dominantly Inherited Alzheimer Network. Of these, 69 were presymptomatic mutation carriers, 50 were symptomatic carriers (31 with Clinical Dementia Rating [CDR] = 0.5, 19 with CDR > 0.5), and 73 were noncarriers from the same families. Voxelbased morphometry was used to identify cross-sectional group differences in gray matter and white matter volume. Results: Significant differences in gray matter (p < 0.05, family-wise error-corrected) were observed between noncarriers and mildly symptomatic (CDR = 0.5) carriers in the thalamus and putamen, as well as in the temporal lobe, precuneus, and cingulate gyrus; the same pattern, but with more extensive changes, was seen in those with CDR > 0.5. Significant white matter differences between noncarriers and symptomatic carriers were observed in the cingulum and fornix; these form input and output connections to the medial temporal lobe, cingulate, and precuneus. No differences between noncarriers and presymptomatic carriers survived correction for multiple comparisons, but there was a trend for decreased gray matter in the thalamus for carriers closer to their estimated age at onset. There were no significant increases of gray or white matter in asymptomatic or symptomatic carriers compared to noncarriers. Conclusions: Atrophy in FAD is observed early, both in areas commonly associated with sporadic Alzheimer disease and also in the putamen and thalamus, 2 regions associated with early amyloid deposition in FAD mutation carriers.

AB - Objective: To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers. Methods: A total of 192 participants with volumetric T1-weighted MRI, genotyping, and clinical diagnosis were available from the Dominantly Inherited Alzheimer Network. Of these, 69 were presymptomatic mutation carriers, 50 were symptomatic carriers (31 with Clinical Dementia Rating [CDR] = 0.5, 19 with CDR > 0.5), and 73 were noncarriers from the same families. Voxelbased morphometry was used to identify cross-sectional group differences in gray matter and white matter volume. Results: Significant differences in gray matter (p < 0.05, family-wise error-corrected) were observed between noncarriers and mildly symptomatic (CDR = 0.5) carriers in the thalamus and putamen, as well as in the temporal lobe, precuneus, and cingulate gyrus; the same pattern, but with more extensive changes, was seen in those with CDR > 0.5. Significant white matter differences between noncarriers and symptomatic carriers were observed in the cingulum and fornix; these form input and output connections to the medial temporal lobe, cingulate, and precuneus. No differences between noncarriers and presymptomatic carriers survived correction for multiple comparisons, but there was a trend for decreased gray matter in the thalamus for carriers closer to their estimated age at onset. There were no significant increases of gray or white matter in asymptomatic or symptomatic carriers compared to noncarriers. Conclusions: Atrophy in FAD is observed early, both in areas commonly associated with sporadic Alzheimer disease and also in the putamen and thalamus, 2 regions associated with early amyloid deposition in FAD mutation carriers.

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