Subregional neuroanatomical change as a biomarker for Alzheimer's disease
Open accessAbstract
Regions of the temporal and parietal lobes are particularly damaged in Alzheimer's disease (AD), and this leads to a predictable pattern of brain atrophy. In vivo quantification of subregional atrophy, such as changes in cortical thickness or structure volume, could lead to improved diagnosis and better assessment of the neuroprotective effects of a therapy. Toward this end, we have developed a fast and robust method for accurately quantifying cerebral structural changes in several cortical and subcortical regions using serial MRI scans. In 169 healthy controls, 299 subjects with mild cognitive impairment (MCI), and 129 subjects with AD, we measured rates of subregional cerebral volume change for each cohort and performed power calculations to identify regions that would provide the most sensitive outcome measures in clinical trials of disease-modifying agents. Consistent with regional specificity of AD, temporal-lobe cortical regions showed the greatest disease-related changes and significantly outperformed any of the clinical or cognitive measures examined for both AD and MCI. Global measures of change in brain structure, including whole-brain and ventricular volumes, were also elevated in AD and MCI, but were less salient when compared to changes in normal subjects. Therefore, these biomarkers are less powerful for quantifying disease-modifying effects of compounds that target AD pathology. The findings indicate that regional temporal lobe cortical changes would have great utility as outcome measures in clinical trials and may also have utility in clinical practice for aiding early diagnosis of neurodegenerative disease.
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Structural MRI studies have shown that NFT deposition is associated with grey matter atrophy resulting from neurodegeneration, and that different tauopathies display distinctive regional patterns of grey matter atrophy.
“Structural MRI studies have shown that NFT deposition is associated with grey matter atrophy that results from neurodegeneration and that different tauopathies display distinctive regional patterns of grey matter atrophy [5][6][7][8].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [7]
The Abstract (page unavailable) says that MRI-detected cortical atrophy parallels the spread of Alzheimer’s disease pathology and that atrophy arises from neuron and synapse loss. It does not specifically link atrophy to NFT deposition or establish distinct atrophy patterns across different tauopathies. (LLM, conf=0.87)
Experimental — accuracy not yet measuredWhen clearly distinguished from potential confounders originating from haem iron, changes in hippocampal T2*-weighted MRI might be a valuable accompaniment to morphological changes in the development of a biomarker for the early stages of Alzheimer's disease.
“When clearly distinguished from potential confounders originating from haem iron, changes in hippocampal T2*-weighted MRI might be a valuable accompaniment to morphological changes in the development of a biomarker for the early stages of Alzheimer’s disease.91”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [91]
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- Authors
- Holland, D., Brewer, J. B., Hagler, D. J., Fennema-Notestine, C., Dale, A. M., Initiative, T. A. D. N., Weiner, M., Thal, L., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J., Toga, A. W., Beckett, L., Green, R. C., Gamst, A., Potter, W. Z., Montine, T., Anders, D., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Shaw, L., Lee, V. M.-Y., Korecka, M., Crawford, K., Neu, S., Harvey, D., Kornak, J., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Vorobik, R., Quinn, J., Schneider, L., Pawluczyk, S., Spann, B., Fleisher, A. S., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Y., Honig, L. S., Bell, K. L., Morris, J. C., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Badger, B., Grossman, H., Tang, C., Stern, J., deToledo-Morrell, L., Shah, R. C., Bach, J., Duara, R., Isaacson, R., Strauman, S., Albert, M. S., Pedroso, J., Toroney, J., Rusinek, H., de Leon, M. J., De Santi, S. M., Doraiswamy, P. M., Petrella, J. R., Aiello, M., Clark, C. M., Pham, C., Nunez, J., Smith, C. D., Given, C. A., Hardy, P., DeKosky, S. T., Oakley, M., Simpson, D. M., Ismail, M. S., Porsteinsson, A., McCallum, C., Cramer, S. C., Mulnard, R. A., McAdams-Ortiz, C., Diaz-Arrastia, R., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Laubinger, M. M., Bartzokis, G., Silverman, D. H. S., Lu, P. H., Fletcher, R., Parfitt, F., Johnson, H., Farlow, M., Herring, S., Hake, A. M., van Dyck, C. H., MacAvoy, M. G., Bifano, L. A., Chertkow, H., Bergman, H., Hosein, C., Black, S., Graham, S., Caldwell, C., Feldman, H., Assaly, M., Hsiung, G.-Y. R., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Gitelman, D., Johnson, N., Mesulam, M., Sadowsky, C., Villena, T., Mesner, S., Aisen, P. S., Johnson, K. B., Behan, K. E., Sperling, R. A., Rentz, D. M., Johnson, K. A., Rosen, A., Tinklenberg, J., Ashford, W., Sabbagh, M., Connor, D., Obradov, S., Killiany, R., Norbash, A., Obisesan, T. O., Jayam-Trouth, A., Wang, P., Auchus, A. P., Huang, J., Friedland, R. P., DeCarli, C., Fletcher, E., Carmichael, O., Kittur, S., Mirje, S., Johnson, S. C., Borrie, M., Lee, T.-Y., Asthana, S., Carlsson, C. M., Potkin, S. G., Highum, D., Preda, A., Nguyen, D., Tariot, P. N., Hendin, B. A., Scharre, D. W., Kataki, M., Beversdorf, D. Q., Zimmerman, E. A., Celmins, D., Brown, A. D., Gandy, S., Marenberg, M. E., Rovner, B. W., Pearlson, G., Blank, K., Anderson, K., Saykin, A. J., Santulli, R. B., Pare, N., Williamson, J. D., Sink, K. M., Potter, H., Ashok Raj, B., Giordano, A., Ott, B. R., Wu, C.-K., Cohen, R., Wilks, K. L., & Safirstein, B. E.
- Affiliations
- University of California San Diego (US)
- Departments of aNeurosciences,
- Radiology, and
- ORCID
- Holland, Dominic
- Hagler, Donald J.
- Weiner, Michael
- Petersen, Ronald
- Jack, Clifford R.
- Jagust, William
- Toga, Arthur W.
- Beckett, Laurel
- Green, Robert C.
- Potter, William Z.
- Felmlee, Joel
- Fox, Nick
- Thompson, Paul
- Alexander, Gene
- Koeppe, Robert A.
- Reiman, Eric M.
- Chen, Kewei
- Lee, Virginia M.-Y.
- Korecka, Magdalena
- Crawford, Karen
- Harvey, Danielle
- Kornak, John
- Frank, Richard
- Snyder, Peter J.
- Kaye, Jeffrey
- Quinn, Joseph
- Schneider, Lon
- Spann, Bryan
- Fleisher, Adam S.
- Heidebrink, Judith L.
- Lord, Joanne L.
- Johnson, Kris
- Stern, Yaakov
- Honig, Lawrence S.
- Bell, Karen L.
- Morris, John C.
- Marson, Daniel
- Tang, Cheuk
- Shah, Raj C.
- Bach, Julie
- Duara, Ranjan
- Isaacson, Richard
- Albert, Marilyn S.
- Rusinek, Henry
- Doraiswamy, P. Murali
- Petrella, Jeffrey R.
- Clark, Christopher M.
- Smith, Charles D.
- Hardy, Peter
- DeKosky, Steven T.
- Ismail, M. Saleem
- Porsteinsson, Anton
- Cramer, Steven C.
- Diaz-Arrastia, Ramon
- DeVous, Michael
- Levey, Allan I.
- Lah, James J.
- Burns, Jeffrey M.
- Silverman, Daniel H. S.
- Lu, Po H.
- Johnson, Heather
- Farlow, Martin
- Hake, Ann M.
- Chertkow, Howard
- Bergman, Howard
- Black, Sandra
- Graham, Simon
- Feldman, Howard
- Hsiung, Ging-Yuek R.
- Kertesz, Andrew
- Bernick, Charles
- Gitelman, Darren
- Mesulam, Marsel
- Sperling, Reisa A.
- Rentz, Dorene M.
- Johnson, Keith A.
- Rosen, Allyson
- Sabbagh, Marwan
- Obisesan, Thomas O.
- Wang, Paul
- Auchus, Alexander P.
- Huang, Juebin
- Friedland, Robert P.
- DeCarli, Charles
- Fletcher, Evan
- Carmichael, Owen
- Johnson, Sterling C.
- Asthana, Sanjay
- Carlsson, Cynthia M.
- Potkin, Steven G.
- Preda, Adrian
- Nguyen, Dana
- Tariot, Pierre N.
- Hendin, Barry A.
- Scharre, Douglas W.
- Kataki, Maria
- Beversdorf, David Q.
- Gandy, Sam
- Rovner, Barry W.
- Pearlson, Godfrey
- Saykin, Andrew J.
- Santulli, Robert B.
- Williamson, Jeff D.
- Sink, Kaycee M.
- Potter, Huntington
- Ott, Brian R.
- Cohen, Ronald
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-12-08
- Volume
- 106
- Issue
- 49
- Pages
- 20954-20959
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2791580
- OpenAlex
- W1583631062
- Cited by
- 210
- References
- 59
- Citations by year
- 2026: 5 · 2024: 7 · 2023: 4 · 2022: 10 · 2021: 12 · 2020: 7 · 2019: 10 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 13 · 2014: 12 · 2013: 21 · 2012: 21
- FWCI
- 16.65
- Type
- journal article
- Language
- en
- Update notices
- correction (2010-03-18)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- GlaxoSmithKline
- National Institute for Health and Care Research (NF-SI-0508-10123)
- National Institutes of Health (n01ns22343-0-0-0, 5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, R01AG22381, R01AG031224, R01AG027342, K01AG030514, R01AG022381, P30AG019610, U19AG010483)
- National Institute of Mental Health (P50MH081755)
- National Institute of Neurological Disorders and Stroke (U54NS056883, P50 NS 22343, N01 NS022343, P50NS022343)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, mild cognitive impairment, structural MRI, temporal lobe, parietal lobe, cortical thickness, brain volume changes, biomarkers, disease-modifying therapy, clinical trial outcome measures, power analysis, early diagnosis, ventriculomegaly
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Demography, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Specificity, Biomarkers, Linear Models, Sample Size
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