Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment
Caselli RJ, Chen K, Lee W, Alexander GE, Reiman EM.. Archives of neurology, 2008-09-01
Topic: Risk, prevention and care in population studies
Background Before symptomatic memory loss, healthy apolipoprotein E epsilon4 (APOE epsilon4) (OMIM 104310) carriers demonstrate accelerated longitudinal decline on memory tests, suggesting the existence of a transitional state between normal aging and mild cognitive impairment (MCI), which we have called amnestic pre-MCI. Objective To support our neuropsychological construct of pre-MCI by characterizing and comparing the relationship between measurements of baseline regional hypometabolism and subsequent rates of memory decline in a group of individuals with neuropsychologically defined asymptomatic memory decline (pre-MCI group) and in nondecliners after controlling for APOE epsilon4 gene dose. Design Longitudinal study. Setting Academic medical center. Participants Of 139 healthy individuals in the Arizona APOE Cohort aged 50 to 69 years who underwent longitudinal neuropsychological testing and fludeoxyglucose F 18-positron emission tomography (FDG-PET) since 1994, 10 met our criteria for amnestic pre-MCI, and 15 showed no decline. Main outcome measures Correlations between lower regional cerebral metabolic rates for glucose (CMRgl) and rates of verbal memory test decline that occurred at a mean of 41 months after baseline FDG-PET using an automated brain mapping algorithm (SPM5). Results The pre-MCI and nondecliner groups did not differ in mean (SD) age (56.8 [4.8] years), education (16.5 [2.3] years), sex (19 women [76%]), or APOE epsilon4 carrier status (12 epsilon4 carriers [48%)]. After controlling for APOE epsilon4 gene dose, the pre-MCI group had significant correlations between lower baseline CMRgl in the posterior cingulate, bilateral parietal, and left prefrontal regions (known to be preferentially affected by Alzheimer disease) and subsequent verbal memory decline. Nondecliners had significant correlations bilaterally in the posterior and midcingulate cortices. Correlations in the left parietal, left temporal, and bilateral frontal regions were significantly greater in the pre-MCI group than those in the nondecliner group. Conclusion Individuals with amnestic pre-MCI showed significantly greater correlations between cerebral hypometabolism and subsequent long-term memory decline than nondecliners in Alzheimer disease-affected brain regions.
Key findings
- Results The pre-MCI and nondecliner groups did not differ in mean (SD) age (56.8 [4.8] years), education (16.5 [2.3] years), sex (19 women [76%]), or APOE epsilon4 carrier status (12 epsilon4 carriers [48%)].
- After controlling for APOE epsilon4 gene dose, the pre-MCI group had significant correlations between lower baseline CMRgl in the posterior cingulate, bilateral parietal, and left prefrontal regions (known to be preferentially affected by Alzheimer disease) and subsequent verbal memory decline.
- Nondecliners had significant correlations bilaterally in the posterior and midcingulate cortices.
- Correlations in the left parietal, left temporal, and bilateral frontal regions were significantly greater in the pre-MCI group than those in the nondecliner group.
- Conclusion Individuals with amnestic pre-MCI showed significantly greater correlations between cerebral hypometabolism and subsequent long-term memory decline than nondecliners in Alzheimer disease-affected brain regions.
Why it matters
In a small group of healthy APOE ε4 carriers with subtle memory decline, lower brain metabolism in certain regions at baseline correlated with faster later memory decline. This supports the idea of a pre-mild cognitive impairment stage, but the sample is very small and it does not show that any treatment alters this decline.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 102 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.1 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 3 / 6 | Cited 6.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Eric M. Reiman: h-index 151 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Arizona: institution h-index 1,336 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18779428) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Caselli, R. J., Chen, K., Lee, W., Alexander, G. E., & Reiman, E. M. (2008). Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. Archives of neurology. https://doi.org/10.1001/archneurol.2008.1
Vancouver
Caselli RJ, Chen K, Lee W, Alexander GE, Reiman EM. Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. Archives of neurology. 2008. doi:10.1001/archneurol.2008.1. PMID: 18779428.
BibTeX
@article{caselli2008-18779428,
author = {Caselli, R. J. and Chen, K. and Lee, W. and Alexander, G. E. and Reiman, E. M.},
title = {{Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment}},
journal = {Archives of neurology},
year = {2008},
doi = {10.1001/archneurol.2008.1},
pmid = {18779428},
url = {https://doi.org/10.1001/archneurol.2008.1}
}
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