Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD
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OBJECTIVE: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI). METHODS: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region. RESULTS: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE epsilon4 allele than in the 16 noncarriers. CONCLUSIONS: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses.
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Individuals with MCI display increased hippocampal activity during memory tasks, which correlates with poor memory performance.
“Individuals with MCI display increased hippocampal activity during memory tasks, which correlates with poor memory performance (Dickerson et al., 2005).”
From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Dickerson et al., 2005
The Results and Discussion (page unavailable) report greater hippocampal activation during a memory task in the MCI group than in older controls. They do not support a correlation with poor memory-task performance: the MCI group performed similarly to controls, and the Results found no significant activation–performance correlation within the MCI group. Across all subjects, greater activation correlated with better performance. (LLM, conf=0.90)
Experimental — accuracy not yet measuredHealthy elderly apoE4 carriers show increased hippocampal and entorhinal activation during encoding task performance.
“Second, healthy elderly apoE4 carriers show increased hippocampal and entorhinal activation during encoding task performance [172, 173].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [172]
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 [172]
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- Authors
- Dickerson, B. C., Salat, D. H., Greve, D. N., Chua, E. F., Rand-Giovannetti, E., Rentz, D. M., Bertram, L., Mullin, K., Tanzi, R. E., Blacker, D., Albert, M. S., & Sperling, R. A.
- Affiliations
- Massachusetts General Hospital (US)
- From the Departments of Neurology (Drs. Dickerson, Bertram, Tanzi, Albert, and Sperling, and E. Rand-Giovannetti and K. Mullin), Psychiatry (Drs. Blacker and Albert), Radiology (Drs. Salat and Greve), and the Athinoula A. Martinos Center for Biomedical Imaging (Drs. Dickerson, Salat, Greve, Blacker, Albert, and Sperling, and E.F. Chua and E. Rand-Giovannetti), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Drs. Dickerson, Rentz, and Sperling, and E.F....
- ORCID
- Venue
- Neurology
- Published
- 2005-08-09
- Volume
- 65
- Issue
- 3
- Pages
- 404-411
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4335677
- OpenAlex
- W2052530454
- Cited by
- 910
- References
- 58
- Citations by year
- 2026: 40 · 2025: 51 · 2024: 40 · 2023: 53 · 2022: 34 · 2021: 43 · 2020: 58 · 2019: 37 · 2018: 47 · 2017: 36 · 2016: 39 · 2015: 36 · 2014: 46 · 2013: 42 · 2012: 53
- FWCI
- 23.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K23AG022509, P01AG04953, K23-AG22509, P50 AG05134, P50AG005134, P01AG004953)
- National Institute of Neurological Disorders and Stroke (K23 NS02189, K23NS002189)
- National Center for Research Resources (P41-RR-14075, P41RR014075)
- NIH Clinical Center
- 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 › Memory and Neural Mechanisms
- Keywords
- mild cognitive impairment, Alzheimer's disease, hippocampal activation, entorhinal cortex, medial temporal lobe, recognition memory, APOE ε4, hippocampal atrophy, normal aging, prodromal Alzheimer's disease
- MeSH terms
- Aged, Aging, Alzheimer Disease, Apolipoproteins E, Cognition Disorders, Female, Genotype, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Neuropsychological Tests, Pattern Recognition, Visual, Genetic Predisposition to Disease
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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