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Neuropathologic substrate of mild cognitive impairment
Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR.. Archives of neurology, 2006-01-01
Topic: Risk, prevention and care in population studies
Objective To define the neuropathologic findings in amnestic mild cognitive impairment (MCI) and early Alzheimer disease (EAD). Methods The mean numbers of diffuse plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs) in 4 neocortical regions and 4 ventromedial temporal lobe regions were counted in 10 patients with amnestic MCI and compared with the mean numbers in 23 normal control subjects and 10 patients with EAD, and then were compared with memory performance. All of the controls and patients were followed longitudinally. Results Patients with MCI showed no significant difference (P>.05) in the number of diffuse plaques from that in normal controls or patients with EAD. In patients with MCI, the number of NPs was significantly elevated in all 4 neocortical regions and amygdala compared with controls (P .05) in the number of NPs between MCI and EAD cerebral cortex, but significant increases were present for NPs in EAD amygdala and subiculum compared with MCI (P Conclusions In patients with amnestic MCI who were followed longitudinally, the early changes of Alzheimer disease were present. The NFTs were slightly more prominent than beta-amyloid peptide deposition in the progression from normal to MCI to EAD. Ventromedial temporal lobe NFTs probably represent the substrate for memory decline in MCI. From a neuropathologic perspective, it appears that amnestic MCI is, in reality, EAD.
Key findings
- Methods The mean numbers of diffuse plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs) in 4 neocortical regions and 4 ventromedial temporal lobe regions were counted in 10 patients with amnestic MCI and compared with the mean numbers in 23 normal control subjects and 10 patients with EAD, and then were compared with memory performance.
- Results Patients with MCI showed no significant difference (P>.05) in the number of diffuse plaques from that in normal controls or patients with EAD.
- In patients with MCI, the number of NPs was significantly elevated in all 4 neocortical regions and amygdala compared with controls (P<.01 to <.001).
Why it matters
In 10 patients with amnestic mild cognitive impairment followed over time, the early brain changes of Alzheimer's disease were already present, with neurofibrillary tangles slightly more prominent than amyloid deposits. This supports the idea that tangles in the ventromedial temporal lobe may underlie memory decline in mild cognitive impairment, but it does not offer a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, 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 | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2006 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 462 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.0 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 5 / 6 | Cited 28.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 56 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author David R. Wekstein: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Kentucky: institution h-index 824 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16401735) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Markesbery, W. R., Schmitt, F. A., Kryscio, R. J., Davis, D. G., Smith, C. D., & Wekstein, D. R. (2006). Neuropathologic substrate of mild cognitive impairment. Archives of neurology. https://doi.org/10.1001/archneur.63.1.38
Vancouver
Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR. Neuropathologic substrate of mild cognitive impairment. Archives of neurology. 2006. doi:10.1001/archneur.63.1.38. PMID: 16401735.
BibTeX
@article{markesbery2006-16401735,
author = {Markesbery, W. R. and Schmitt, F. A. and Kryscio, R. J. and Davis, D. G. and Smith, C. D. and Wekstein, D. R.},
title = {{Neuropathologic substrate of mild cognitive impairment}},
journal = {Archives of neurology},
year = {2006},
doi = {10.1001/archneur.63.1.38},
pmid = {16401735},
url = {https://doi.org/10.1001/archneur.63.1.38}
}
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