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Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline
Open accessAbstract
Objective: To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline. Methods: Amyloid-positive participants with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSpMRI], limbic predominant [LPMRI], typical AD [tADMRI]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models. Results: When participants were divided categorically, the HpSpMRI group showed significantly more AD-like hypometabolism on 18F-fluorodeoxyglucose-PET (p < 0.05) and poorer baseline executive function (p < 0.001). Other baseline clinical measures did not differ across the 3 groups. Participants with HpSpMRI also showed faster subsequent clinical decline than participants with LPMRI on the Alzheimer9s Disease Assessment Scale, 13-Item Subscale (ADAS-Cog13), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tADMRI on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog13 score (p < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy. Conclusions: AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation.
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“For instance, patients with LOAD often branch into distinct groups including (i) slow versus rapid cognitive decliners (7), (ii) amnestic versus nonamnestic AD (8), (iii) executive versus cortical visual defect versus dysphasia-predominant AD (9), (iv) psychosis and depression-associated AD (10–12), and (v) metabolic dysfunction–associated AD modulated by abnormalities in insulin resistance, Hormo”
From Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets (2021) · cites this paper as [7]
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“For instance, patients with LOAD often branch into distinct groups including (i) slow versus rapid cognitive decliners (7), (ii) amnestic versus nonamnestic AD (8), (iii) executive versus cortical visual defect versus dysphasia-predominant AD (9), (iv) psychosis and depression-associated AD (10–12), and (v) metabolic…”
Background
Metadata
- Authors
- Risacher, S. L., Anderson, W. H., Charil, A., Castelluccio, P. F., Shcherbinin, S., Saykin, A. J., Schwarz, A. J., Initiative, F. T. A. D. N., Initiative, A. D. N., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Petersen, R., Aisen, P., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Balasubramanian, A. B., Mason, J., Sim, I., Beckett, L., Harvey, D., Donohue, M., Jack, C. R., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Jagust, W., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Morris, J. C., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Shaw, L. M., Trojanowki, J. Q., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., National, N. B., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Petersen, R., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Morris, J. C., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Love, M. N., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Duara, R., Varon, D., Greig, M. T., Roberts, P., Albert, M., Onyike, C., D’Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Pogorelec, D. M., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, M. P., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Arnold, S. E., Karlawish, J. H., Wolk, D., Clark, C. M., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H. S., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Brosch, J. R., Herring, S., Hunt, C., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Robin Hsiung, G.-Y., Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M.-M., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C.-K., Johnson, N., Sadowsky, C., Villena, T., Turner, R. S., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T.-Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Kertesz, A., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Boles Ponto, L. L., Shim, H., Smith, K. E., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B. A., & Fargher, K.
- Affiliations
- Eli Lilly (United States) (US)
- ORCID
- Risacher, Shannon L.
- Charil, Arnaud
- Shcherbinin, Sergey
- Schwarz, Adam J.
- Weiner, Michael W.
- Green, Robert C.
- Paul, Steven
- Davies, Peter
- Fillit, Howard
- Hefti, Franz
- Snyder, Peter
- Schwartz, Adam
- Thomas, Ronald G.
- Walter, Sarah
- Balasubramanian, Archana B.
- Harvey, Danielle
- Fox, Nick
- Thompson, Paul
- Vemuri, Prashanthi
- Jones, David
- Kantarci, Kejal
- Koeppe, Robert A.
- Reiman, Eric M.
- Chen, Kewei
- Korecka, Magdalena
- Crawford, Karen
- Foroud, Tatiana M.
- Shen, Li
- Faber, Kelley
- Kim, Sungeun
- Nho, Kwangsik
- Hsiao, John
- Kaye, Jeffrey
- Silbert, Lisa
- Schneider, Lon S.
- Heidebrink, Judith L.
- Lord, Joanne L.
- Knopman, David
- Johnson, Kris
- Stern, Yaakov
- Honig, Lawrence S.
- Bell, Karen L.
- Ances, Beau
- Carroll, Maria
- Franklin, Erin
- Oliver, Angela
- Marson, Daniel
- Clark, David
- Geldmacher, David
- Roberson, Erik
- Love, Marissa Natelson
- Shah, Raj C.
- Duara, Ranjan
- Albert, Marilyn
- D’Agostino, Daniel
- Kielb, Stephanie
- Galvin, James E.
- Cerbone, Brittany
- Rusinek, Henry
- Glodzik, Lidia
- Petrella, Jeffrey R.
- Wong, Terence Z.
- Arnold, Steven E.
- Karlawish, Jason H.
- Wolk, David
- Clark, Christopher M.
- Smith, Charles D.
- Hardy, Peter
- Sinha, Partha
- Porsteinsson, Anton P.
- Ismail, M. Saleem
- Thai, Gaby
- Womack, Kyle
- Quiceno, Mary
- Levey, Allan I.
- Lah, James J.
- Burns, Jeffrey M.
- Swerdlow, Russell H.
- Brooks, William M.
- Apostolova, Liana
- Silverman, Daniel H.S.
- Lu, Po H.
- Johnson, Heather
- Farlow, Martin R.
- Hake, Ann Marie
- Brosch, Jared R.
- Carson, Richard E.
- Chertkow, Howard
- Bergman, Howard
- Stefanovic, Bojana
- Feldman, Howard
- Bernick, Charles
- Bonakdarpour, Borna
- Kerwin, Diana
- Turner, Raymond Scott
- Sperling, Reisa A.
- Johnson, Keith A.
- Marshall, Gad
- Yesavage, Jerome
- Taylor, Joy L.
- Lane, Barton
- Rosen, Allyson
- Sabbagh, Marwan N.
- Belden, Christine M.
- Jacobson, Sandra A.
- Kowall, Neil
- Killiany, Ronald
- Budson, Andrew E.
- Norbash, Alexander
- Obisesan, Thomas O.
- Lerner, Alan
- Tatsuoka, Curtis
- Maillard, Pauline
- Olichney, John
- Carmichael, Owen
- Johnson, Sterling
- Asthana, Sanjay
- Carlsson, Cynthia M.
- Preda, Adrian
- Nguyen, Dana
- Tariot, Pierre
- Burke, Anna
- Scharre, Douglas W.
- Kataki, Maria
- Pearlson, Godfrey D.
- Flashman, Laura A.
- Hynes, Mary L.
- Santulli, Robert B.
- Sink, Kaycee M.
- Williamson, Jeff D.
- Ott, Brian R.
- Tremont, Geoffrey
- Salloway, Stephen
- Correia, Stephen
- Miller, Bruce L.
- Perry, David
- Mintzer, Jacobo
- Bachman, David
- Pasternak, Stephen
- Pomara, Nunzio
- Schultz, Susan K.
- Shim, Hyungsub
- Relkin, Norman
- Ravdin, Lisa
- Smith, Amanda
- Venue
- Neurology
- Published
- 2017-11-21
- Volume
- 89
- Issue
- 21
- Pages
- 2176-2186
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC5696639
- OpenAlex
- W2766047614
- Cited by
- 163
- References
- 33
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 20 · 2023: 15 · 2022: 29 · 2021: 21 · 2020: 24 · 2019: 18 · 2018: 7
- FWCI
- 11.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, P30AG010129, P30AG010133, K01AG049050, R01AG054076, U01AG032984, R01AG019771, R44AG049540)
- National Cancer Institute (R01CA129769)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015922)
- U.S. National Library of Medicine (R01LM011360)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- hippocampal sparing, cortical atrophy, hippocampal volume, executive function, FDG-PET hypometabolism, volumetric MRI, cognitive decline
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Cognition Disorders, Cross-Sectional Studies, Female, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Peptide Fragments, Regression Analysis, Amyloid beta-Peptides
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