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An August 2024 report from the Lancet Commission on dementia highlights approaches that, if fully implemented, could prevent or delay up to 45% of dementia cases.[1] Convened by the Lancet, an international medical journal based in the United Kingdom, the commission identified factors contributing to dementia that are often modifiable without drugs.
The risks recently added to the list of 14 potentially modifiable factors are untreated vision loss and high LDL (“bad”) cholesterol, the type...
An August 2024 report from the Lancet Commission on dementia highlights approaches that, if fully implemented, could prevent or delay up to 45% of dementia cases.[1] Convened by the Lancet, an international medical journal based in the United Kingdom, the commission identified factors contributing to dementia that are often modifiable without drugs.
The risks recently added to the list of 14 potentially modifiable factors are untreated vision loss and high LDL (“bad”) cholesterol, the type of cholesterol that can build up in the arteries and increase a person’s risk of heart attack and stroke. The 12 other modifiable risk factors, previously identified in the 2020 Lancet Commission report, are less education, head injury, physical inactivity, smoking, excessive alcohol consumption, hypertension, obesity, diabetes, hearing loss, depression, infrequent social contact and air pollution.
According to the 2024 report, “The potential for prevention is high and, overall, nearly half of dementias could theoretically be prevented by eliminating these 14 risk factors. These findings provide hope.”
Background on dementia
Approximately 6.7 million older U.S. adults suffer from dementia. By 2060 that number is expected to increase to 14 million.[2] Although dementia affects about 11% of Americans aged 65 years or older and is strongly correlated with increasing age, it is not a normal part of aging.[3]
Alzheimer’s disease is the most common form of dementia, representing 60-80% of cases. The second leading form is vascular dementia, including stroke-related dementia, which accounts for 5-10% of cases. Other forms of dementia include those associated with Lewy body protein deposits or damage to the nerve cells in the frontal and temporal regions of the brain. More than one of these forms of dementia can occur simultaneously.
The pathophysiology of dementia remains uncertain, and there are no curative therapies. Of the FDA-approved drugs for Alzheimer’s disease, Public Citizen’s Health Research Group has classified lecanemab (LEQEMBI) and donanemab (KISUNLA) as Do Not Use because of their marginal effects in slowing disease progression and the risk of potentially fatal brain bleeding.[4],[5],[6],[7] We have classified the acetylcholinesterase inhibitor donepezil (ARICEPT, ARICEPT 23 and generics), the first FDA-approved drug exclusively for Alzheimer’s disease, as Do Not Use because its minimal effectiveness makes its risks unacceptable.[8],[9] Better drugs for Alzheimer’s disease and other forms of dementia are urgently needed.
The Lancet Commission report
For the 2024 report, the members of the Lancet Commission agreed on the best available evidence, prioritizing systematic reviews, meta-analyses and recent data and conducting new meta-analyses. The report synthesizes data spanning many decades and millions of individual patients to develop a comprehensive “life course perspective of dementia prevention” that considered the relative importance of a variety of plausible risk factors. Although most of the evidence was from wealthier nations, global data were assessed. The commission found that low- and mid-income nations, and minority populations internationally, were especially burdened by modifiable risk factors for dementia.
To place all modifiable risk factors into a single quantitative model, the commission estimated the relative contribution of each of the 14 factors using the best global data they could identify. To adjust for known overlap between factors (for example, depression can lead to social isolation and vice versa, and correlations exist between inactivity, diabetes, hypertension and obesity), the commission used data from a longitudinal Norwegian database of 37,000 participants aged 45 years and older. The Table below shows the estimates from those calculations. For example, eliminating high LDL cholesterol in midlife could reduce future dementia cases by up to 7%, and eliminating untreated vision loss in late life could reduce dementia cases by up to 2%.
Table: Lancet Commission’s Estimate of the Percentage Reduction in Dementia Cases if a Risk Factor Is Completely Eliminated
| Life Stage | Modifiable Factor | % |
|---|---|---|
| Early life | Less education | 5 |
| Midlife (18-65 years) | Hearing loss | 7 |
| High LDL cholesterol* | 7 | |
| Depression | 3 | |
| Traumatic brain injury | 3 | |
| Physical inactivity | 2 | |
| Diabetes | 2 | |
| Smoking | 2 | |
| Hypertension | 2 | |
| Obesity | 1 | |
| Excessive alcohol consumption | 1 | |
| Late Life | Social isolation | 5 |
| Air pollution | 3 | |
| Untreated vision loss* | 2 | |
| Overall | 45 |
Source: 2024 Lancet Commission report on dementia
*Newly added by the 2024 Commission report
The Lancet Commission also considered other potentially addressable dementia risk factors but did not include them, because the available evidence was insufficient or inconsistent. These included too little sleep, an unhealthy diet, infections and mental health conditions.
Newly identified risk factors for dementia
The two recently added and potentially modifiable risk factors for dementia were high LDL cholesterol and untreated vision loss.
Several observational studies including millions of participants found that increased LDL cholesterol significantly correlates with increased (by 5-33%) dementia rates in the later years of life. A potential link between LDL cholesterol and dementia may be that high levels of LDL cholesterol in the blood increase the risk of stroke and Alzheimer’s-related protein deposits in the brain. A recent study found that counseling about diet and exercise has a small effect on reducing LDL cholesterol, and a meta-analysis of 36 cohort studies of people taking statins found that the drugs were associated with an average 20% reduction in dementia risk. However, a Cochrane review of randomized clinical trials found that statin medications given in late life were not similarly protective against dementia (one study) or more general cognitive decline (two studies).
Vision loss as a forerunner of dementia was evident from a recent meta-analysis of 14 studies involving more than 6 million older adults with fully intact cognition at baseline. Over the subsequent 4-15 years, 171,888 of these adults developed dementia. Vision loss increased the risk of dementia by a statistically adjusted average of 47%. Another meta-analysis found that cataracts and diabetic neuropathy were significantly associated with eventual dementia, although age-related macular degeneration and glaucoma were not. A U.S. study followed 3,038 people (all older than 65 years and cognitively healthy at baseline) with cataracts for more than 20 years. After statistical adjustments for age, race, APOE genotype (a biomarker of heightened risk for Alzheimer’s dementia), education, smoking and several comorbidities, people whose cataracts were extracted showed an average 29% reduction in their dementia risk. Possible mechanisms for the observed linkage between vision loss and dementia include underlying illness that simultaneously attacks the eyes and the brain, or the effects of sensory loss itself.
What You Can Do
Some of the actions that the Lancet Commission recommended to reduce dementia risk can be taken by individuals. These actions include expanding the use of eyewear to protect against injury from solar ultraviolet radiation and health education about the importance of effective diabetes care to reduce the risk of permanent vision loss and other complications of the disease.
Other recommendations require actions by society, health systems and governments, such as making screening and treatment for hearing and depression accessible to all and improving opportunities for quality education.
Specific actions to address the newly identified risk factors include strategies to prevent, detect and treat high LDL cholesterol (including diet and exercise) during midlife and making screening and treatment for vision loss accessible for all.
References
[1] Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024 Aug 10;404(10452):572-628.
[2] Centers for Disease Control and Prevention. Alzheimer’s disease and dementia. About Dementia. August 17, 2024. https://www.cdc.gov/alzheimers-dementia/about/index.html. Accessed November 4, 2024.
[3] Centers for Disease Control and Prevention. Alzheimer’s disease and dementia. Signs and symptoms of dementia. August 14, 2024. https://www.cdc.gov/alzheimers-dementia/signs-symptoms/index.html. Accessed November 4, 2024.
[4] Worst Pills, Best Pills News. Lecanemab for Alzheimer’s disease: do not use. October 2023. https://www.worstpills.org/newsletters/view/1556. Accessed November 4, 2024.
[5] Worst Pills, Best Pills News. Donanemab (KISUNLA): a bad choice for alzheimer’s disease. November 2024. https://www.worstpills.org/newsletters/view/1626. Accessed November 4, 2024.
[6] Koutsodendris N, Nelson MR, Rao A, Huang Y. Apolipoprotein E and Alzheimer's disease: findings, hypotheses, and potential mechanisms. Annu Rev Pathol. 2022;17:73-99.
[7] Eli Lilly. Label: donanemab-azbt (KISUNLA). July 2024. https://uspl.lilly.com/kisunla/kisunla.html#s15. Accessed November 5, 2024.
[8] Sharma K. Cholinesterase inhibitors as Alzheimer's therapeutics (review). Mol Med Rep. 2019 Aug;20(2):1479-1487.
[9] Worst Pills, Best Pills News. Drug profile: cholinesterase inhibitors. July 31, 2024. https://www.worstpills.org/monographs/view/128. Accessed November 42024.
