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The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders
Nithianantharajah J, Hannan AJ.. Progress in neurobiology, 2009-10-09
Topic: Risk, prevention and care in population studies
The concept of 'cognitive reserve', and a broader theory of 'brain reserve', were originally proposed to help explain epidemiological data indicating that individuals who engaged in higher levels of mental and physical activity via education, occupation and recreation, were at lower risk of developing Alzheimer's disease and other forms of dementia. Subsequently, behavioral, cellular and molecular studies in animals (predominantly mice and rats) have revealed dramatic effects of environmental enrichment, which involves enhanced levels of sensory, cognitive and motor stimulation via housing in novel, complex environments. Furthermore, increasing levels of voluntary physical exercise, via ad libitum access to running wheels, can have significant effects on brain and behavior, thus informing the relative effects of mental and physical activity. More recently, animal models of brain disorders have been compared under environmentally stimulating and standard housing conditions, and this has provided new insights into environmental modulators and gene-environment interactions involved in pathogenesis. Here, we review animal studies that have investigated the effects of modifying mental and physical activity via experimental manipulations, and discuss their relevance to brain and cognitive reserve (BCR). Recent evidence suggests that the concept of BCR is not only relevant to brain aging, neurodegenerative diseases and dementia, but also to other neurological and psychiatric disorders. Understanding the cellular and molecular mechanisms mediating BCR may not only facilitate future strategies aimed at optimising healthy brain aging, but could also identify molecular targets for novel pharmacological approaches aimed at boosting BCR in 'at risk' and symptomatic individuals with various brain disorders.
Key findings
- The concept of 'cognitive reserve', and a broader theory of 'brain reserve', were originally proposed to help explain epidemiological data indicating that individuals who engaged in higher levels of mental and physical activity via education, occupation and recreation, were at lower risk of developing Alzheimer's disease and other forms of dementia.
- Subsequently, behavioral, cellular and molecular studies in animals (predominantly mice and rats) have revealed dramatic effects of environmental enrichment, which involves enhanced levels of sensory, cognitive and motor stimulation via housing in novel, complex environments.
- Furthermore, increasing levels of voluntary physical exercise, via ad libitum access to running wheels, can have significant effects on brain and behavior, thus informing the relative effects of mental and physical activity.
- Recent evidence suggests that the concept of BCR is not only relevant to brain aging, neurodegenerative diseases and dementia, but also to other neurological and psychiatric disorders.
Why it matters
This review describes animal studies showing that environmental enrichment and voluntary physical exercise can have significant effects on brain and behavior, informing the concepts of brain and cognitive reserve. The evidence comes mainly from animals such as mice and rats, so it does not establish that mental or physical activity prevents dementia in people.
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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 (Progress in neurobiology) |
| Journal's citation record | 3 / 4 | Progress in Neurobiology: journal h-index 325 (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 | 1 / 5 | 2009 — within 20 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 | 6 / 7 | Cited 324 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.1 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 6.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Anthony John Hannan: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Wellcome Sanger Institute: institution h-index 1,844 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19819293) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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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
Nithianantharajah, J., & Hannan, A. J. (2009). The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders. Progress in neurobiology. https://doi.org/10.1016/j.pneurobio.2009.10.001
Vancouver
Nithianantharajah J, Hannan AJ. The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders. Progress in neurobiology. 2009. doi:10.1016/j.pneurobio.2009.10.001. PMID: 19819293.
BibTeX
@article{nithianantharajah2009-19819293,
author = {Nithianantharajah, J. and Hannan, A. J.},
title = {{The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders}},
journal = {Progress in neurobiology},
year = {2009},
doi = {10.1016/j.pneurobio.2009.10.001},
pmid = {19819293},
url = {https://doi.org/10.1016/j.pneurobio.2009.10.001}
}
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