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Does lithium prevent Alzheimer's disease?
Forlenza OV, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF.. Drugs & aging, 2012-05-01
Topic: Amyloid, tau and blood-test diagnosis
Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.
Key findings
- In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement.
- A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum.
Why it matters
This review discusses evidence that lithium may have neuroprotective effects, and notes one placebo-controlled trial in amnestic mild cognitive impairment where long-term lithium may have slowed progression of cognitive and functional deficits. The authors suggest lithium may have disease-modifying effects, but this is presented as a possibility rather than established.
Study details
- Evidence strengthLow
How this study scored 42/100
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 (Drugs & aging) |
| Journal's citation record | 1 / 4 | Drugs & Aging: journal h-index 135 (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 | 2012 — 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 | 5 / 7 | Cited 173 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.8 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Wagner F. Gattaz: h-index 75 (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 22500970) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Forlenza, O. V., de Paula, V. J., Machado-Vieira, R., Diniz, B. S., & Gattaz, W. F. (2012). Does lithium prevent Alzheimer's disease? Drugs & aging. https://doi.org/10.2165/11599180-000000000-00000
Vancouver
Forlenza OV, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF. Does lithium prevent Alzheimer's disease? Drugs & aging. 2012. doi:10.2165/11599180-000000000-00000. PMID: 22500970.
BibTeX
@article{forlenza2012-22500970,
author = {Forlenza, O. V. and de Paula, V. J. and Machado-Vieira, R. and Diniz, B. S. and Gattaz, W. F.},
title = {{Does lithium prevent Alzheimer's disease?}},
journal = {Drugs \& aging},
year = {2012},
doi = {10.2165/11599180-000000000-00000},
pmid = {22500970},
url = {https://doi.org/10.2165/11599180-000000000-00000}
}
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