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Lesions without symptoms: understanding resilience to Alzheimer disease neuropathological changes
Gómez-Isla T, Frosch MP.. Nature reviews. Neurology, 2022-03-24
Topic: Amyloid, tau and blood-test diagnosis
Since the original description of amyloid-β plaques and tau tangles more than 100 years ago, these lesions have been considered the neuropathological hallmarks of Alzheimer disease (AD). The prevalence of plaques, tangles and dementia increases with age, and the lesions are considered to be causally related to the cognitive symptoms of AD. Current schemes for assessing AD lesion burden examine the distribution, abundance and characteristics of plaques and tangles at post mortem, yielding an estimate of the likelihood of cognitive impairment. Although this approach is highly predictive for most individuals, in some instances, a striking mismatch between lesions and symptoms can be observed. A small subset of individuals harbour a high burden of plaques and tangles at autopsy, which would be expected to have had devastating clinical consequences, but remain at their cognitive baseline, indicating 'resilience'. The study of these brains might provide the key to understanding the 'black box' between the accumulation of plaques and tangles and cognitive impairment, and show the way towards disease-modifying treatments for AD. In this Review, we begin by considering the heterogeneity of clinical manifestations associated with the presence of plaques and tangles, and then focus on insights derived from the rare yet informative individuals who display high amounts of amyloid and tau deposition in their brains (observed directly at autopsy) without manifesting dementia during life. The resilient response of these individuals to the gradual accumulation of plaques and tangles has potential implications for assessing an individual's risk of AD and for the development of interventions aimed at preserving cognition.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Gómez-Isla, T., & Frosch, M. P. (2022). Lesions without symptoms: understanding resilience to Alzheimer disease neuropathological changes. Nature reviews. Neurology. https://doi.org/10.1038/s41582-022-00642-9
Vancouver
Gómez-Isla T, Frosch MP. Lesions without symptoms: understanding resilience to Alzheimer disease neuropathological changes. Nature reviews. Neurology. 2022. doi:10.1038/s41582-022-00642-9. PMID: 35332316.
BibTeX
@article{gomezisla2022-35332316,
author = {Gómez-Isla, T. and Frosch, M. P.},
title = {{Lesions without symptoms: understanding resilience to Alzheimer disease neuropathological changes}},
journal = {Nature reviews. Neurology},
year = {2022},
doi = {10.1038/s41582-022-00642-9},
pmid = {35332316},
url = {https://doi.org/10.1038/s41582-022-00642-9}
}
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Key findings
- In this Review, we begin by considering the heterogeneity of clinical manifestations associated with the presence of plaques and tangles, and then focus on insights derived from the rare yet informative individuals who display high amounts of amyloid and tau deposition in their brains (observed directly at autopsy) without manifesting dementia during life.
Why it matters
This review discusses rare individuals who have a high burden of amyloid plaques and tau tangles at autopsy but remain at their cognitive baseline, a state described as resilience. Studying these brains might help explain the link between these lesions and cognitive impairment and point toward disease-modifying treatments.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Neurology) |
| Journal's citation record | 3 / 4 | Nature Reviews Neurology: journal h-index 269 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 96 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.0 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 3.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 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 Matthew P. Frosch: h-index 120 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (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 35332316) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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