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Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals
Petersen RC, Smith GE, Ivnik RJ, Tangalos EG, Schaid DJ, Thibodeau SN, Kokmen E, Waring SC et al.. JAMA, 1995-04-01
Topic: Amyloid, tau and blood-test diagnosis
Objective The outcome of patients with mild cognitive impairment is not known, yet these patients present a difficult dilemma for the clinician. This study was designed to characterize the outcome of a group of patients with mild cognitive impairment and to determine whether the presence of the epsilon 4 allele on the apolipoprotein E gene (APOE) is a predictor of that outcome. Design A prospective, longitudinal inception cohort. Setting General community clinic. Participants A consecutive sample of 66 patients who met criteria for a diagnosis of a mild cognitive impairment and who had at least one clinical reevaluation was identified from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry. Interventions We evaluated patients initially and at 12- to 18-month intervals up to 54 months using standard neurological and neuropsychological measures such as the Mini-Mental State Examination, the Dementia Rating Scale, the Wechsler Adult Intelligence Scale--Revised, the Wechsler Memory Scale--Revised, and the Free and Cued Selective Reminding Test. The APOE status of study patients was determined. Main outcome measure The development of dementia as determined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. Results Sixty-six individuals had been reevaluated once (mean of 18 months), 36 individuals twice (mean of 36 months), and 22 individuals on three occasions (mean of 54 months), with conversion rates to dementia at these intervals of 24%, 44%, and 55%, respectively. A multivariate Cox regression model demonstrated that possession of an APOE epsilon 4 allele was the strongest predictor of clinical outcome. Conclusions These data suggest the following: (1) patients with mild cognitive impairment can be clinically defined, (2) many members of this group progress to Alzheimer's disease, and (3) APOE epsilon 4 allele status appears to be a strong predictor of clinical progression.
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APA 7th
Petersen, R. C., Smith, G. E., Ivnik, R. J., Tangalos, E. G., Schaid, D. J., Thibodeau, S. N., et al. (1995). Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. JAMA. https://doi.org/10.1001/jama.1995.03520400044042
Vancouver
Petersen RC, Smith GE, Ivnik RJ, Tangalos EG, Schaid DJ, Thibodeau SN, et al. Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. JAMA. 1995. doi:10.1001/jama.1995.03520400044042. PMID: 7646655.
BibTeX
@article{petersen1995-7646655,
author = {Petersen, R. C. and Smith, G. E. and Ivnik, R. J. and Tangalos, E. G. and Schaid, D. J. and Thibodeau, S. N. and Kokmen, E. and Waring, S. C. and others},
title = {{Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals}},
journal = {JAMA},
year = {1995},
doi = {10.1001/jama.1995.03520400044042},
pmid = {7646655},
url = {https://doi.org/10.1001/jama.1995.03520400044042}
}
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Key findings
- Results Sixty-six individuals had been reevaluated once (mean of 18 months), 36 individuals twice (mean of 36 months), and 22 individuals on three occasions (mean of 54 months), with conversion rates to dementia at these intervals of 24%, 44%, and 55%, respectively.
- A multivariate Cox regression model demonstrated that possession of an APOE epsilon 4 allele was the strongest predictor of clinical outcome.
Why it matters
In 66 people with mild cognitive impairment from the Mayo Clinic Alzheimer's Disease Patient Registry, followed for up to 54 months, 24% had developed dementia at about 18 months, 44% at 36 months (36 people re-seen) and 55% at 54 months (22 people re-seen). In a multivariate analysis, carrying an APOE ε4 allele was "the strongest predictor of clinical outcome", but the summary gives no measure of how much it raised risk. This is an observational study of who progressed; it did not test any treatment and does not show that APOE status decides any one person's outcome.
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Study details
- Study designlongitudinal study
- Participants66
- Evidence strengthModerate
How this study scored 68/100
Published in a top-tier journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 1995 — older than 20 years, still counted |
| Sample size | 1 / 4 | 66 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 764 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.2 citations a year over 33 year(s) since 1995 |
| Impact for its field and year | 5 / 6 | Cited 22.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 61 other studies in this library |
| Still being cited | 2 / 4 | Cited 24 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Ronald Carl Petersen: h-index 209 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (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 7646655) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 68 / 100 | — |
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