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Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD
Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL.. Neurology, 2005-03-01
Topic: Risk, prevention and care in population studies
Objective To test the hypotheses 1) that whole-brain volume decline begins in early adulthood, 2) that cross-sectional and longitudinal atrophy estimates agree in older, nondemented individuals, and 3) that longitudinal atrophy accelerates in the earliest stages of Alzheimer disease (AD). Methods High-resolution, high-contrast structural MRIs were obtained from 370 adults (age 18 to 97). Participants over 65 (n = 192) were characterized using the Clinical Dementia Rating (CDR) as either nondemented (CDR 0, n = 94) or with very mild to mild dementia of the Alzheimer type (DAT, CDR 0.5 and 1, n = 98). Of these older participants, 79 belonged to a longitudinal cohort and were imaged again a mean 1.8 years after baseline. Estimates of gray matter (nGM), white matter (nWM), and whole-brain volume (nWBV) normalized for head sizes were generated based on atlas registration and image segmentation. Results Hierarchical regression of nWBV estimates from nondemented individuals across the adult lifespan revealed a strong linear, moderate quadratic pattern of decline beginning in early adulthood, with later onset of nWM than nGM loss. Whole-brain volume differences were detected by age 30. The cross-sectional atrophy model overlapped with the rates measured longitudinally in older, nondemented individuals (mean decline of -0.45% per year). In those individuals with very mild DAT, atrophy rate more than doubled (-0.98% per year). Conclusions Nondemented individuals exhibit a slow rate of whole-brain atrophy from early in adulthood with white-matter loss beginning in middle age; in older adults, the onset of dementia of the Alzheimer type is associated with a markedly accelerated atrophy rate.
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APA 7th
Fotenos, A. F., Snyder, A. Z., Girton, L. E., Morris, J. C., & Buckner, R. L. (2005). Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology. https://doi.org/10.1212/01.wnl.0000154530.72969.11
Vancouver
Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL. Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology. 2005. doi:10.1212/01.wnl.0000154530.72969.11. PMID: 15781822.
BibTeX
@article{fotenos2005-15781822,
author = {Fotenos, A. F. and Snyder, A. Z. and Girton, L. E. and Morris, J. C. and Buckner, R. L.},
title = {{Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD}},
journal = {Neurology},
year = {2005},
doi = {10.1212/01.wnl.0000154530.72969.11},
pmid = {15781822},
url = {https://doi.org/10.1212/01.wnl.0000154530.72969.11}
}
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Key findings
- Results Hierarchical regression of nWBV estimates from nondemented individuals across the adult lifespan revealed a strong linear, moderate quadratic pattern of decline beginning in early adulthood, with later onset of nWM than nGM loss.
- Conclusions Nondemented individuals exhibit a slow rate of whole-brain atrophy from early in adulthood with white-matter loss beginning in middle age; in older adults, the onset of dementia of the Alzheimer type is associated with a markedly accelerated atrophy rate.
Why it matters
In 370 adults aged 18 to 97, this MRI study found that whole-brain volume declines slowly with normal aging, starting in early adulthood (differences were "detected by age 30"). In older people without dementia the loss averaged about 0.45% of brain volume per year. In people with very mild Alzheimer-type dementia it was 0.98% per year, "more than doubled". These are group averages for a reference baseline, not a diagnostic test for one person, and the study tested no treatment.
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Study details
- Study designcross-sectional
- Participants192
- Effect size0.45%; 0.98%
- Evidence strengthModerate
How this study scored 67/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for 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 | 4 / 12 | A snapshot of people at one point in 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 | 2005 — older than 20 years, still counted |
| Sample size | 2 / 4 | 192 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 586 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.5 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 9.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 3 / 4 | Cited 69 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Randy L. Buckner: h-index 150 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Howard Hughes Medical Institute: institution h-index 2,008 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15781822) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 67 / 100 | — |
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