Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease
Open accessAbstract
Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimer's disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T1-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimer's disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%, sensitivity 90%, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of Alzheimer's disease, these three measures demonstrated an area under the curve of 1.0. The three magnetic resonance imaging measures demonstrated significant correlations with clinical and neuropsychological assessments as well as with cerebrospinal fluid levels of tau, hyperphosphorylated tau and abeta 42 proteins. These results demonstrate that automated magnetic resonance imaging measures can serve as an in vivo surrogate for disease severity, underlying neuropathology and as a non-invasive diagnostic method for mild cognitive impairment and Alzheimer's disease.
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Aβ pathology distribution showed an expected fronto-temporal predominant pattern.
“In contrast, Aβ pathology distribution showed an expected [6, 32] fronto-temporal predominant pattern (Fig. 2A–C, Supp. Figure 2, online resource).”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [6]
The Discussion (page unavailable) describes Aβ-associated amyloid changes in the entorhinal cortex and neocortical regions, which supports a temporal component. It does not describe frontal involvement as predominant or establish a fronto-temporal distribution; the study's Results report MRI measures rather than a map of Aβ pathology. (LLM, conf=0.83)
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References 51 · Cited by 405
Research works printed but not linked: 2
- Kemper TL Albert M Knoefel J Neuroanatomical and neuropathological changes in normal aging and in dementia Clinical neurology of aging 1994 New York Oxford University Press 3 78
- Lezak MD Neuropsychological Assessment 1995 Oxford Oxford University Press
- Authors
- Desikan, R. S., Cabral, H. J., Hess, C. P., Dillon, W. P., Glastonbury, C. M., Weiner, M. W., Schmansky, N. J., Greve, D. N., Salat, D. H., Buckner, R. L., Fischl, B., & Initiative, A. D. N.
- Affiliations
- Boston University (US)
- University of California, San Francisco (US)
- San Francisco VA Medical Center (US)
- Massachusetts General Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fischl, B.
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-05-21
- Volume
- 132
- Issue
- 8
- Pages
- 2048-2057
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2714061
- OpenAlex
- W1529992670
- Cited by
- 405
- References
- 51
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 18 · 2023: 20 · 2022: 18 · 2021: 23 · 2020: 18 · 2019: 16 · 2018: 35 · 2017: 33 · 2016: 21 · 2015: 27 · 2014: 34 · 2013: 38 · 2012: 33
- FWCI
- 18.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Brain (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion)
- OpenBU (Boston University) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- Alzheimer's Association (AG05681, 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)
- Eisai (U01 AG024904, AG024904)
- National Institutes of Health (5u01ag024904-10, BIRN002, U01-AG024904, AG05681, RR14075, AG024904, AG 03991)
- National Institute on Aging (U01-AG-024904, AG021910, R01AG021910, P50AG005681, P01AG003991, R01AG034556)
- National Institute of Biomedical Imaging and Bioengineering (R01EB001550, U01 AG024904, EB001550, AG024904)
- National Center for Research Resources (RR16594, RR 14075, U24RR021382, R01 RR1659401A1, RR021382, P41RR014075, BIRN002, R01RR016594, U01 AG024904)
- 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
- mild cognitive impairment, Alzheimer's disease, automated MRI segmentation, entorhinal cortex thickness, hippocampal volume, early diagnosis, tau protein, hyperphosphorylated tau, amyloid-beta 42, cerebrospinal fluid biomarkers, non-invasive diagnosis
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain Mapping, Cerebral Cortex, Cognition Disorders, Epidemiologic Methods, Female, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Prognosis, Biomarkers, Disease Progression, Early Diagnosis, Young Adult
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