Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline
Open accessAbstract
OBJECTIVE: To use functional MRI (fMRI) to investigate whether hippocampal activation during a memory task can predict cognitive decline in individuals with mild cognitive impairment (MCI). METHODS: 25 older individuals with MCI performed a visual scene encoding task during fMRI scanning, and were followed clinically for at least 4 years after scanning. A hypothesis driven analysis of fMRI data was performed. First, fMRI data were analysed at the group level to identify the regions of the hippocampal formation that were engaged by this memory task. Parameter estimates of each subject's memory related hippocampal activation (% signal change) were extracted and were analysed with a linear regression model to determine whether hippocampal activation predicted the degree or rate of cognitive decline, as measured by change in Clinical Dementia Rating Sum-of-Boxes (CDR-SB). RESULTS: Over 5.9 (1.2) years of follow-up after scanning, subjects varied widely in degree and rate of cognitive decline (change in CDR-SB ranged from 0 to 6, and the rate ranged from 0 to 1 CDR-SB unit/year). Greater hippocampal activation predicted greater degree and rate of subsequent cognitive decline (p<0.05). This finding was present even after controlling for baseline degree of impairment (CDR-SB), age, education and hippocampal volume, as well as gender and apolipoprotein E status. In addition, an exploratory whole brain analysis produced convergent results, demonstrating that the hippocampal formation was the only brain region where activation predicted cognitive decline. CONCLUSIONS: In individuals with MCI, greater memory task related hippocampal activation is predictive of a greater degree and rate of cognitive decline subsequent to scanning. fMRI may provide a physiological imaging biomarker useful for identifying the subgroup of MCI individuals at highest risk of cognitive decline for potential inclusion in disease modifying clinical trials.
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Greater hippocampal activation during encoding tasks is associated with worse task performance in MCI and AD patients.
“Greater hippocampal activation during encoding tasks is associated with worse task performance [176] in MCI and AD patients [172, 177]”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [177]
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- Authors
- Miller, S. L., Fenstermacher, E., Bates, J., Blacker, D., Sperling, R. A., & Dickerson, B. C.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Dickerson, B C
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2007-10-10
- Volume
- 79
- Issue
- 6
- Pages
- 630-635
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC2683145
- OpenAlex
- W2140731175
- Cited by
- 241
- References
- 42
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 10 · 2023: 10 · 2022: 7 · 2021: 9 · 2020: 14 · 2019: 9 · 2018: 4 · 2017: 9 · 2016: 13 · 2015: 17 · 2014: 22 · 2013: 13 · 2012: 19
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institute on Aging (K23AG022509, R01AG029411, P01AG004953)
- National Institute of Neurological Disorders and Stroke (K23NS002189)
- National Center for Research Resources (P41RR014075)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
- Keywords
- mild cognitive impairment, hippocampal activation, cognitive decline prediction, hippocampal formation, memory encoding, Clinical Dementia Rating, imaging biomarkers, Alzheimer's disease, older adults, apolipoprotein E, disease-modifying trials
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Pattern Recognition, Visual, Mental Recall, Linear Models, Disease Progression
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