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Coevolution of white matter hyperintensities and cognition in the elderly
Maillard P, Carmichael O, Fletcher E, Reed B, Mungas D, DeCarli C.. Neurology, 2012-07-18
Topic: Risk, prevention and care in population studies
Objective To investigate the effects of baseline white matter hyperintensity (WMH) and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). Methods A total of 150 individuals including cognitively normal elderly individuals and those with Alzheimer disease and mild cognitive impairment completed serial episodic memory and executive function evaluations and serial MRI scans sufficient for longitudinal measurement of WMH (mean delay 4.0 years). Incident WMH voxels were categorized as extended (baseline WMH that grew larger) or emergent (newly formed WMH). We used a stepwise regression approach to investigate the effects of baseline WMH and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). Results WMH burden significantly increased over time, and approximately 80% of incident WMH voxels represented extensions of existing lesions. Each 1 mL/y increase in WMH extension was associated with an additional 0.70 SD/y of subsequent episodic memory decrease (p = 0.0053) and an additional 0.55 SD/y of subsequent executive function decrease (p = 0.022). Emergent WMHs were not found to be associated with a change in cognitive measures. Conclusions Aging-associated WMHs evolve significantly over a 4-year period. Most of this evolution represents worsening injury to the already compromised surround of existing lesions. Increasing WMH was also significantly associated with declining episodic memory and executive function. This finding supports the view that white matter disease is an insidious and continuously evolving process whose progression has clinically relevant cognitive consequences.
Key findings
- Results WMH burden significantly increased over time, and approximately 80% of incident WMH voxels represented extensions of existing lesions.
- Each 1 mL/y increase in WMH extension was associated with an additional 0.70 SD/y of subsequent episodic memory decrease (p = 0.0053) and an additional 0.55 SD/y of subsequent executive function decrease (p = 0.022).
- Emergent WMHs were not found to be associated with a change in cognitive measures.
- Conclusions Aging-associated WMHs evolve significantly over a 4-year period.
- Increasing WMH was also significantly associated with declining episodic memory and executive function.
Why it matters
Over about four years, growth of existing white matter hyperintensities was linked to faster decline in episodic memory and executive function, while newly appearing hyperintensities were not linked to cognitive change. This suggests that worsening of already-present white matter injury, rather than new spots, tracks with cognitive decline.
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Study details
- Study designlongitudinal study
- Participants150
- Evidence strengthModerate
How this study scored 62/100
Published in a leading specialty 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 | 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 | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 150 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 | 5 / 7 | Cited 174 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.9 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 9.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Charles S DeCarli: h-index 150 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Davis: institution h-index 1,257 (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 22815562) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Maillard, P., Carmichael, O., Fletcher, E., Reed, B., Mungas, D., & DeCarli, C. (2012). Coevolution of white matter hyperintensities and cognition in the elderly. Neurology. https://doi.org/10.1212/wnl.0b013e3182617136
Vancouver
Maillard P, Carmichael O, Fletcher E, Reed B, Mungas D, DeCarli C. Coevolution of white matter hyperintensities and cognition in the elderly. Neurology. 2012. doi:10.1212/wnl.0b013e3182617136. PMID: 22815562.
BibTeX
@article{maillard2012-22815562,
author = {Maillard, P. and Carmichael, O. and Fletcher, E. and Reed, B. and Mungas, D. and DeCarli, C.},
title = {{Coevolution of white matter hyperintensities and cognition in the elderly}},
journal = {Neurology},
year = {2012},
doi = {10.1212/wnl.0b013e3182617136},
pmid = {22815562},
url = {https://doi.org/10.1212/wnl.0b013e3182617136}
}
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