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Rates of decline in Alzheimer disease decrease with age
Holland D, Desikan RS, Dale AM, McEvoy LK, Alzheimer’s Disease Neuroimaging Initiative.. PloS one, 2012-08-02
Topic: Amyloid, tau and blood-test diagnosis
Age is the strongest risk factor for sporadic Alzheimer disease (AD), yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and cognitively healthy (HC) individuals aged 65 to 90 years (total n = 723). The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Aβ(1-42), tau, and phospho-tau(181p) (ptau), showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old. Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.
Key findings
- These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old.
- Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.
Why it matters
Rates of clinical decline and brain atrophy in Alzheimer's disease and mild cognitive impairment decreased with older age, while healthy controls showed the opposite pattern. This implies that Alzheimer's appears milder in people older than about 85, which could make it harder to distinguish from normal aging and reduce the power of trials including older participants.
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Study details
- Study designlongitudinal study
- Participants723
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed 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. We have no data on senior author's track record, so that was left out: it earned 55 of the 96 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (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 | 723 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 | 4 / 7 | Cited 99 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.2 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 7.0× 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 | 1 / 4 | Cited 8 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 of California San Diego: institution h-index 1,852 (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 22876315) |
| Free to read | 2 / 2 | Free to read |
| Points | 55 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 55 of the 96 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
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
Holland, D., Desikan, R. S., Dale, A. M., McEvoy, L. K., & Alzheimer’s Disease Neuroimaging Initiative. (2012). Rates of decline in Alzheimer disease decrease with age. PloS one. https://doi.org/10.1371/journal.pone.0042325
Vancouver
Holland D, Desikan RS, Dale AM, McEvoy LK, Alzheimer’s Disease Neuroimaging Initiative. Rates of decline in Alzheimer disease decrease with age. PloS one. 2012. doi:10.1371/journal.pone.0042325. PMID: 22876315.
BibTeX
@article{holland2012-22876315,
author = {Holland, D. and Desikan, R. S. and Dale, A. M. and McEvoy, L. K. and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Rates of decline in Alzheimer disease decrease with age}},
journal = {PloS one},
year = {2012},
doi = {10.1371/journal.pone.0042325},
pmid = {22876315},
url = {https://doi.org/10.1371/journal.pone.0042325}
}
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