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(Pre)diabetes, brain aging, and cognition
S Roriz-Filho J, Sá-Roriz TM, Rosset I, Camozzato AL, Santos AC, Chaves ML, Moriguti JC, Roriz-Cruz M.. Biochimica et biophysica acta, 2008-12-16
Topic: Risk, prevention and care in population studies
Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy. In fact, diabetes subjects are more prone to develop extense and earlier-than-usual leukoaraiosis (White Matter High-Intensity Lesions - WMHL). WMHL are usually present at different degrees in brain scans of elderly people. People with more advanced WMHL are at increased risk for executive dysfunction, cognitive impairment and dementia. Clinical phenotypes associated with insulin resistance possibly represent true clinical models for brain and systemic aging.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
S Roriz-Filho, J., Sá-Roriz, T. M., Rosset, I., Camozzato, A. L., Santos, A. C., Chaves, M. L., et al. (2009). (Pre)diabetes, brain aging, and cognition. Biochimica et biophysica acta. https://doi.org/10.1016/j.bbadis.2008.12.003
Vancouver
S Roriz-Filho J, Sá-Roriz TM, Rosset I, Camozzato AL, Santos AC, Chaves ML, et al. (Pre)diabetes, brain aging, and cognition. Biochimica et biophysica acta. 2009. doi:10.1016/j.bbadis.2008.12.003. PMID: 19135149.
BibTeX
@article{srorizfilho2009-19135149,
author = {S Roriz-Filho, J. and Sá-Roriz, T. M. and Rosset, I. and Camozzato, A. L. and Santos, A. C. and Chaves, M. L. and Moriguti, J. C. and Roriz-Cruz, M.},
title = {{(Pre)diabetes, brain aging, and cognition}},
journal = {Biochimica et biophysica acta},
year = {2009},
doi = {10.1016/j.bbadis.2008.12.003},
pmid = {19135149},
url = {https://doi.org/10.1016/j.bbadis.2008.12.003}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD).
- Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain.
- Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE).
- People with more advanced WMHL are at increased risk for executive dysfunction, cognitive impairment and dementia.
- Clinical phenotypes associated with insulin resistance possibly represent true clinical models for brain and systemic aging.
Why it matters
This review describes how prediabetes, diabetes, and the metabolic syndrome are associated with increased risk of cognitive decline and dementia, including Alzheimer's disease, and discusses possible mechanisms such as advanced glycation endproducts, oxidative stress, and insulin resistance. It is a summary of evidence and hypotheses, not a report of a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 45/100
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. We have no data on journal's citation record, so that was left out: it earned 43 of the 96 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochimica et biophysica acta) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 387 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.4 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 11.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 40 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Matheus Roriz‐Cruz: h-index 13 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universidade de São Paulo: institution h-index 936 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19135149) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 43 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 43 of the 96 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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Read the original
- DOI: 10.1016/j.bbadis.2008.12.003
- PubMed: 19135149
- Original source →
- Free full text: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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