Regional rates of neocortical atrophy from normal aging to early Alzheimer disease
Open accessAbstract
OBJECTIVE: To evaluate the spatial pattern and regional rates of neocortical atrophy from normal aging to early Alzheimer disease (AD). METHODS: Longitudinal MRI data were analyzed using high-throughput image analysis procedures for 472 individuals diagnosed as normal, mild cognitive impairment (MCI), or AD. Participants were divided into 4 groups based on Clinical Dementia Rating Sum of Boxes score (CDR-SB). Annual atrophy rates were derived by calculating percent cortical volume loss between baseline and 12-month scans. Repeated-measures analyses of covariance were used to evaluate group differences in atrophy rates across regions as a function of impairment. Planned comparisons were used to evaluate the change in atrophy rates across levels of disease severity. RESULTS: In patients with MCI-CDR-SB 0.5-1, annual atrophy rates were greatest in medial temporal, middle and inferior lateral temporal, inferior parietal, and posterior cingulate. With increased impairment (MCI-CDR-SB 1.5-2.5), atrophy spread to parietal, frontal, and lateral occipital cortex, followed by anterior cingulate cortex. Analysis of regional trajectories revealed increasing rates of atrophy across all neocortical regions with clinical impairment. However, increases in atrophy rates were greater in early disease within medial temporal cortex, whereas increases in atrophy rates were greater at later stages in prefrontal, parietal, posterior temporal, parietal, and cingulate cortex. CONCLUSIONS: Atrophy is not uniform across regions, nor does it follow a linear trajectory. Knowledge of the spatial pattern and rate of decline across the spectrum from normal aging to Alzheimer disease can provide valuable information for detecting early disease and monitoring treatment effects at different stages of disease progression.
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The pattern of brain atrophy is closely related to regional NFT accumulation found in Alzheimer's disease patients and is quite different from the pattern of amyloid plaques.
“The pattern of brain atrophy is closely related to regional NFT accumulation found in AD patients (and quite different to the pattern of amyloid plaques) (Braak and Braak, 1991, McDonald et al., 2009), and thus atrophy remains a valuable biomarker in the evaluation of tau based therapeutics.”
From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as McDonald et al., 2009
The Abstract and Discussion describe regional patterns of atrophy in MCI and early AD, but do not compare those patterns with neurofibrillary tangles or amyloid plaques. Searches for NFT accumulation and amyloid plaques found no passage in our copy addressing the claimed relationship. (LLM, conf=0.74)
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- Authors
- McDonald, C. R., McEvoy, L. K., Gharapetian, L., Fennema-Notestine, C., Hagler, D. J., Holland, D., Koyama, A., Brewer, J. B., & Dale, A. M.
- Affiliations
- University of California San Diego (US)
- From the Department of Psychiatry (C.R.M., C.F.-N.), Multimodal Imaging Laboratory (C.R.M., L.K.M., L.G., C.F.-N., D.J.H., D.H., A.K., J.B.B., A.M.D.), Department of Radiology (L.K.M., D.J.H., D.H., J.B.B., A.M.D.), and Department of Neurosciences (J.B.B., A.M.D.), University of California, San Diego, CA.
- Venue
- Neurology
- Published
- 2009-08-11
- Volume
- 73
- Issue
- 6
- Pages
- 457-465
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2727145
- OpenAlex
- W1974681848
- Cited by
- 299
- References
- 4
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 14 · 2023: 8 · 2022: 14 · 2021: 21 · 2020: 17 · 2019: 20 · 2018: 20 · 2017: 16 · 2016: 17 · 2015: 24 · 2014: 21 · 2013: 21 · 2012: 19
- FWCI
- 15.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health (U01AG024904, AG024904)
- Alzheimer's Association (U01 AG024904)
- Bristol-Myers Squibb (U01 AG024904, AG024904)
- Eli Lilly and Company (U01 AG024904, AG024904)
- Pfizer (AG024904, U01 AG024904)
- AstraZeneca
- GlaxoSmithKline
- Alzheimer's Disease Neuroimaging Initiative (U01AG024904, AG024904)
- Novartis Pharmaceuticals Corporation (U01 AG024904, AG024904)
- Northern California Institute for Research and Education (U01 AG024904)
- Elan (U01 AG024904)
- Eisai (U01 AG024904, AG024904)
- National Institutes of Health (n01mh22005-16-0-1, 5r01ag024506-03, 5u01ag024904-10, 5r43ns061023-02, U01-AG024904, AG024904)
- University of California, Los Angeles
- University of California, San Diego
- National Institute on Aging (U01-AG-024904, R01AG031224, R01-AG024506, AG 024904, R01AG022381, K01AG029218, U19AG010483, 1U01AG024904-02)
- National Institute of Mental Health (N01 MH-22005, MH079146-01A2, K01MH079146, R01MH079752, P50MH081755, P30MH062512)
- National Institute of Neurological Disorders and Stroke (U54NS056883, K23NS056091, 2 R01 NS18741-23A1, NS056091, 5R43NS061023, 1R43NS061023, K23NS050305, P50NS022343, R01NS018741)
- National Institute of Biomedical Imaging and Bioengineering (U01 AG024904, AG024904)
- National Center for Research Resources (U24RR021992, U24RR021382, U24 RR21382, U01 AG024904, U24RR019701)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- Alzheimer's disease, mild cognitive impairment, normal aging, medial temporal lobe, posterior cingulate cortex, inferior parietal cortex, anterior cingulate cortex, disease progression, Clinical Dementia Rating
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Atrophy, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Disease Progression, Neocortex, Early Diagnosis
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