Some medical conditions are so feared and widespread that a diagnosis can devastate individuals and families. The distress and dread caused by a diagnosis of Alzheimer’s disease is a prime example. It is one of the main reasons why I have personally written about potential solutions, recognizing the profound suffering caused by dementia and the desperate need for change.
The Alzheimer’s Disease Crisis
Increasing rates of Alzheimer’s disease and dementia are an ongoing crisis. Currently, six million individuals in the United states have Alzheimer’s disease or other forms of dementia with estimates suggesting rates will increase to 13 million by 2050 (ADA 2023). Shockingly, around 33% of seniors already die with the condition. Financial costs are estimated at around $345 billion and are expected to mushroom to $1 trillion by 2050 (ADA 2023). And beyond the financial costs, dementia is overwhelming for loved ones and their families, causing immeasurable emotional pain and suffering. As it stands, we desperately need new, effective treatments to help turn the tide of this devastating condition.
Recent “Game-Changing” Treatments
While newer pharmaceutical treatments are touted as “game changers” that decrease the rate of progression of the disease, the published data does not hold up well to scrutiny. The newest of these approved drugs, lecanemab or Leqembi, had over one-third of patients drop out of a recent clinical trial due to brain swelling, which in more severe cases, can be life threatening (Swanson 2021). The authors still somehow claimed the drug was “well tolerated.”
Also worth noting, the treated patients did not show cognitive improvement, the drug only slowed the progression of the disease by about 30% on average. These results do not portend an overly promising treatment, especially considering the high costs for the drug, which sits around $25,000 per year and is not expected to be covered by insurance.
Yet other promising approaches to dementia prevention and treatment continue to be almost completely ignored by the medical establishment and mainstream media.
Lithium Shows Promise for Dementia
For years, research has been building that suggests that lithium can play a role in the prevention of dementia and Alzheimer’s disease. Initially, research on bipolar disorder documented a stunning reduction in dementia with patients given lithium as treatment (Kessing 2008). And continuing research confirms the initial findings, showing that lithium treatment for bipolar disorder decreases the risk of dementia by half in treated patients (Velosa 2020).
Based on the initial findings, researchers have started to explore the clinical effects of lithium on dementia patients directly. Initial findings were somewhat mixed, likely due to attempts at treating more severe cases or treatment regimens that were too short to produce significant results. Yet as the research has continued, the data has begun to show benefits. To date, some of the most interesting outcomes are from the Forlenza study, initially published in 2011 and with follow-up data published again in 2019 and 2023.
The Forlenza Study
The Forlenza study focused on treating early stages of dementia, termed mild cognitive impairment. The researchers wanted to see if long-term lithium treatment could improve outcomes and prevent the progression to dementia and Alzheimer’s disease. The initial published data followed patients for a year. The findings showed a modest decrease in cognitive decline with a reduction in levels of a marker for brain tangles with lithium treatment (Forlenza 2011). To better assess long-term outcomes, the researchers continued to follow the study subjects.
A follow-up publication in 2019 found that the lithium-treated patients remained cognitively stable for two years while the placebo group continued to decline (Forlenza 2019). Trends for better survival were also present in those treated with lithium as compared to controls. In addition, the researchers found that lithium appeared to help prevent brain plaques in those with less plaque to begin with, but had less effect in patients with higher levels. The results further highlight the potential for the prevention of dementia with lithium, but the difficulty of direct treatment once more significant pathology has set in.
In 2023 the researchers again followed up with participants a total of 13 years later, with results becoming more impressive since the initial findings. The average Mini-Mental State Exam (MMSE) scores were low normal in subjects who had taken lithium. For those individuals on placebo, however, their average scores indicated moderate levels of dementia (25.5 versus 18.3). Verbal fluency test scores were also strikingly different. Subjects who had taken lithium scored 34.4 as compared to placebo subjects at 11.6. The differences were statistically large, showing the promise of lithium as a preventative treatment (Damiano 2023).
The increasing rates of dementia are a crisis that threatens to overwhelm our medical system, economy and society at large. The huge financial and emotional burden of care needed for individuals struggling with dementia is already devastating and bankrupting households and families. Unfortunately, current drug strategies are not likely to make an effective difference. In order to stem the tide we need to take a more comprehensive approach to dementia prevention, using strategies that are already proven to decrease the incidence and reduce the severity of the condition. And one strategy that already has clear evidence of benefits is lithium.
Lithium has been shown to improve cognitive function, reduce inflammation, and protect neurons from damage, with benefits already born out in the Forlenza study among others. Lithium is also relatively safe and well tolerated, especially considering that it is typically used in lower doses for prevention. It has the potential to make a significant difference in the lives of millions of people affected by this devastating condition.
It’s well past time that we expand our treatment approach to decrease the future burden of Alzheimer’s disease. And with lithium, we can start to finally make a difference.
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Alzheimer’s Disease Association. 2023 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2023;19(4). doi:10.1002/alz.13016
Damiano RF, Loureiro JC, Pais MV, et al. Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment. Braz J Psychiatry. 2023;45(1):46-49. Published 2023 Mar 11. doi:10.47626/1516-4446-2022-2767
Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011;198(5):351-356. doi:10.1192/bjp.bp.110.080044
Forlenza OV, Radanovic M, Talib LL, Gattaz WF. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. Br J Psychiatry. 2019;215(5):668-674. doi:10.1192/bjp.2019.76
Kessing LV, Søndergård L, Forman JL, Andersen PK. Lithium treatment and risk of dementia. Arch Gen Psychiatry. 2008;65(11):1331-1335. doi:10.1001/archpsyc.65.11.1331
Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody [published correction appears in Alzheimers Res Ther. 2022 May 21;14(1):70]. Alzheimers Res Ther. 2021;13(1):80. Published 2021 Apr 17. doi:10.1186/s13195-021-00813-8
Velosa J, Delgado A, Finger E, Berk M, Kapczinski F, de Azevedo Cardoso T. Risk of dementia in bipolar disorder and the interplay of lithium: a systematic review and meta-analyses. Acta Psychiatr Scand. 2020;141(6):510-521. doi:10.1111/acps.13153