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Brain structural alterations before mild cognitive impairment
Abstract
OBJECTIVE: To determine whether alterations of brain structure in normal aged individuals precede the development of mild cognitive impairment (MCI) or Alzheimer disease (AD). BACKGROUND: Persons with MCI and AD demonstrate cortical volume losses vs asymptomatic aged individuals, particularly in the hippocampus, amygdala, and entorhinal cortex. It is unknown whether these losses or other volumetric changes are present, and to what degree, in cognitively normal individuals before the clinical diagnosis of MCI. METHODS: Structural MRI was performed on a cross-section of 136 longitudinally examined normal aged subjects. All subjects were cognitively normal at the time of their scan, but 23 later developed MCI, and 9 of these 23 went on to an AD diagnosis. Extracted volumes from voxel-based morphometric analysis were combined with clinical data to compare the 23 subjects who eventually developed MCI to 113 subjects who remained cognitively normal over an average follow-up of 5.4 years. RESULTS: Initially normal subjects who eventually developed MCI demonstrated decreased gray matter volumes in the anteromedial temporal lobes bilaterally and left angular gyrus while still cognitively normal. CONCLUSION: Structural brain changes in anatomic areas involved in higher cognitive processes precede clinical signs and symptoms in longitudinally followed normal subjects destined to develop mild cognitive impairment.
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“The interval between initial ADD clinical diagnosis and death is approximately 8 years (129), but AβPs and NFTs are present well over a decade before death (130-138).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [132]
In the citing paper
“Using MRI, this atrophy is detectable prior to the diagnosis of AD, at the stage of amnestic Mild Cognitive Impairment (aMCI) (Convit et al., 1997; Shi et al., 2009) or even earlier, in asymptomatic elderly up to 10 years before the diagnosis of dementia (Smith et al., 2007; Tondelli et al., 2012).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Smith et al., 2007
Citations
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980
Voxel-Based Morphometry—The Methods
Ashburner, J., & Friston, K. J. (2000) · NeuroImage · doi:10.1006/nimg.2000.0582 · Cited by 8,676
Winblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L. ‐., Nordberg, A., Bäckman, L., Albert, M., Almkvist, O., et al. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01380.x · Cited by 4,946
Thresholding of statistical maps in functional neuroimaging using the false discovery rate
Genovese, C. R., Lazar, N. A., & Nichols, T. (2002) · NeuroImage · doi:10.1006/nimg.2001.1037 · Cited by 4,923
A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains
Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N. A., Friston, K. J., & Frackowiak, R. S. J. (2001) · NeuroImage · doi:10.1006/nimg.2001.0786 · Cited by 4,561
Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00056-0 · Cited by 1,656
Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment
Jack, C. R., Petersen, R. C., Xu, Y. C., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Waring, S. C., Tangalos, E. G., & Kokmen, E. (1999) · Neurology · doi:10.1212/wnl.52.7.1397 · Cited by 1,404
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366
Voxel-Based Morphometry of the Human Brain: Methods and Applications
Mechelli, A., Price, C. J., Friston, K. J., & Ashburner, J. (2005) · Current Medical Imaging Formerly Current Medical Imaging Reviews · doi:10.2174/1573405054038726 · Cited by 894
Research works printed but not linked: 4
- Petersen RC. Clinical subtypes of Alzheimer's disease. Dement Geriatr Cogn Disord 1998;9 Suppl 3:16–24.
- Morris JC. Mild cognitive impairment and preclinical Alzheimer's disease. Geriatrics 2005;Suppl:9–14.
- Menzel HJ, Kladetzky RG, Assmann G. Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis 1983;3:310–315.
- Braak H, Braak E. Alzheimer's disease starts in early adulthood. Neurobiol Aging 1998;19:S78.
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Huang, L., Smith, A., Cummings, P. T., Kendall, E. J., & Obenaus, A. (2009) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21661 · Cited by 9
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Aine, C. J., Adair, J. C., Knoefel, J. E., Sanfratello, L., & Stephen, J. M. (2019) · Springer eBooks · doi:10.1007/978-3-319-62657-4_31-1 · Cited by 1
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Cholerton, B., Skinner, J. S., & Baker, L. D. (2014) · Wiley eBooks · doi:10.1002/9781118730676.ch28
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Sun, Y., Liu, Y., & Liu, B. (2022) · International Conference on Bioinformatics and Computational Biology (ICBCB) · doi:10.1109/icbcb55259.2022.9802479
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Metadata
- Authors
- Smith, C. D., Chebrolu, H., Wekstein, D. R., Schmitt, F. A., Jicha, G. A., Cooper, G., & Markesbery, W. R.
- Affiliations
- From the Departments of Neurology (C.D.S., H.C., F.A.S., G.A.J., W.R.M.), Anatomy and Neurobiology (C.D.S., W.R.M.), Pathology (W.R.M.), Behavioral Science (F.A.S.), Psychiatry (F.A.S.), and Psychology (F.A.S.), Magnetic Resonance Imaging and Spectroscopy Center (C.D.S., H.C.), and Alzheimer's Disease Center and Sanders-Brown Center on Aging (C.D.S., D.R.W., F.A.S., G.A.J., G.C., W.R.M.), University of Kentucky College of Medicine, Lexington.
- Venue
- Neurology
- Published
- 2007-04-17
- Volume
- 68
- Issue
- 16
- Pages
- 1268-1273
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2020623898
- Cited by
- 161
- References
- 49
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 2 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 13 · 2012: 14
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Kentucky
- National Institute on Aging (P30AG028383)
- National Institute of Neurological Disorders and Stroke (5R01 NS-36660, R01NS036660)
- National Center for Research Resources (5M01RR02602, M01RR002602)
- 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
- mild cognitive impairment, Alzheimer's disease, brain structural changes, gray matter loss, angular gyrus, hippocampus, amygdala, entorhinal cortex, normal aging, prodromal Alzheimer's disease, voxel-based morphometry
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cognition, Cognition Disorders, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neural Pathways, Parietal Lobe, Predictive Value of Tests, Temporal Lobe, Disease Progression
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