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Cognitive reserve and clinical progression in Alzheimer disease: A paradoxical relationship
van Loenhoud AC, van der Flier WM, Wink AM, Dicks E, Groot C, Twisk J, Barkhof F, Scheltens P et al.. Neurology, 2019-07-02
Topic: Amyloid, tau and blood-test diagnosis
Objective To investigate the relationship between cognitive reserve (CR) and clinical progression across the Alzheimer disease (AD) spectrum. Methods We selected 839 β-amyloid (Aβ)-positive participants with normal cognition (NC, n = 175), mild cognitive impairment (MCI, n = 437), or AD dementia (n = 227) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). CR was quantified using standardized residuals (W scores) from a (covariate-adjusted) linear regression with global cognition (13-item Alzheimer's Disease Assessment Scale-cognitive subscale) as an independent variable of interest, and either gray matter volumes or white matter hyperintensity volume as dependent variables. These W scores, reflecting whether an individual's degree of cerebral damage is lower or higher than clinically expected, were tested as predictors of diagnostic conversion (i.e., NC to MCI/AD dementia, or MCI to AD dementia) and longitudinal changes in memory (ADNI-MEM) and executive functions (ADNI-EF). Results The median follow-up period was 24 months (interquartile range 6-42). Corrected for age, sex, APOE4 status, and baseline cerebral damage, higher gray matter volume-based W scores (i.e., greater CR) were associated with a lower diagnostic conversion risk (hazard ratio [HR] 0.22, p p p p = 0.038; ADNI-MEM: β = 0.52, p = 0.028; ADNI-EF: β = 0.42, p = 0.077) and MCI (diagnostic conversion: HR 0.21, p p = 0.003; ADNI-EF: β = 0.59, p p = 0.002; ADNI-EF: β = -0.77, p = 0.081). Conclusions Among Aβ-positive individuals, greater CR related to attenuated clinical progression in predementia stages of AD, but accelerated cognitive decline after the onset of dementia.
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APA 7th
van Loenhoud, A. C., van der Flier, W. M., Wink, A. M., Dicks, E., Groot, C., Twisk, J., et al. (2019). Cognitive reserve and clinical progression in Alzheimer disease: A paradoxical relationship. Neurology. https://doi.org/10.1212/wnl.0000000000007821
Vancouver
van Loenhoud AC, van der Flier WM, Wink AM, Dicks E, Groot C, Twisk J, et al. Cognitive reserve and clinical progression in Alzheimer disease: A paradoxical relationship. Neurology. 2019. doi:10.1212/wnl.0000000000007821. PMID: 31266904.
BibTeX
@article{vanloenhoud2019-31266904,
author = {van Loenhoud, A. C. and van der Flier, W. M. and Wink, A. M. and Dicks, E. and Groot, C. and Twisk, J. and Barkhof, F. and Scheltens, P. and others},
title = {{Cognitive reserve and clinical progression in Alzheimer disease: A paradoxical relationship}},
journal = {Neurology},
year = {2019},
doi = {10.1212/wnl.0000000000007821},
pmid = {31266904},
url = {https://doi.org/10.1212/wnl.0000000000007821}
}
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Key findings
- Results The median follow-up period was 24 months (interquartile range 6-42).
- Corrected for age, sex, APOE4 status, and baseline cerebral damage, higher gray matter volume-based W scores (i.e., greater CR) were associated with a lower diagnostic conversion risk (hazard ratio [HR] 0.22, p < 0.001) and slower decline in memory (β = 0.48, p < 0.001) and executive function (β = 0.67, p < 0.001).
Why it matters
In amyloid-positive participants, greater cognitive reserve based on gray matter volume was linked to lower risk of progressing to mild cognitive impairment or Alzheimer's dementia. However, once symptoms appeared, higher cognitive reserve was also associated with faster subsequent decline, so its role in progression is complex.
Study details
- Study designlongitudinal study
- Participants175
- Effect sizeHR 0.21
- Evidence strengthModerate
How this study scored 71/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for randomized / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 68 of the 96 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 175 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 148 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.4 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 11.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 62 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31266904) |
| Free to read | 2 / 2 | Free to read |
| Points | 68 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 68 of the 96 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
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