Scientists identify 2 new risk factors for dementia

The number of modifiable risk factors definitively linked to dementia has been updated from 12 to 14, according to the Lancet Commission on dementia, prevention, intervention, and care. Research conducted following the last update in 2020 demonstrated that vision loss and high levels of low-density lipoprotein (LDL or “bad”) cholesterol are now on the commission’s list.

The lengthy update, authored by Gill Livingston, MD, of University College London and colleagues was published July 2024 in the prestigious medical journal The Lancet. It was also presented at the annual Alzheimer Association Conference.

In the commission review of almost 600 scientific publications, they found that if health management addressed all these factors, the worldwide risk for dementia would fall to 55% of its current level.

The report states that high LDL cholesterol causes about 7% of dementia risk, making it one of the more significant risk factors. Unaddressed hearing loss also accounts for about 7% of dementia risk, while social isolation, and lesser education are tied for third place on the list, each contributing about 5% of the risk. Other modifiable risk factors account for 3% or less of someone’s risk for dementia.

Other risk factors are still under investigation

The commission’s review examined other factors which may be linked to dementia, but the research was insufficient to definitively associate them with risk for dementia. These included diet, insufficient sleep, and neuropsychiatric conditions such as psychotic and bipolar disorders. The research lacked evidence that interventions treating these factors would lessen dementia risk.

The commission also studied several direct interventions, including:

• Diagnostic scans and screens
• Symptomatic treatments (usually drugs which do not alter the disease process)
• Anticholinesterase inhibitor drugs
• Anti-amyloid biologic drugs

The commission described symptomatic treatments as having shot-term, modest positive effects, but when they stopped treatment long-term outcomes were worse. Unfortunately, the researchers also described the unfavorable effects of anti-amyloid drugs like donanemab (Kisunla) and lecanemab (Leqembi).

“Currently, the effects of all [anti-amyloid] drugs are small. The resources required to support early biomarker-based diagnosis, supervision of administration and safety, and buying the drugs will mean that rollouts into many health systems will be slow or non-existent in some,” the team writes in their report.

The European Medicines Agency recently rejected lecanemab for use in Europe for Alzheimer’s disease.

Several of the same authors, including Livingston, wrote a separate report, published in The Lancet Healthy Longevity. It contains a cost-benefit analysis of policies addressing six dementia risk factors and applying them across the United Kingdom. These included:

• Drinking alcohol
• Dietary salt
• Dietary sugar
• Automobile pollution
• Smoking
• Youth head trauma

The analysis also scrutinized interventions previously tested in a variety of settings:

• Raising alcohol prices
• Raising cigarette prices
• Reducing salt and sugar in commercial foods
• Banning cars from certain areas
• Mandating the use of bike helmets

The authors then estimated the monetary costs and associated quality-adjusted life years (QALYs) gained if implemented in the English population.

So, for example, raising the price of alcohol by an amount that, in Scotland, would cut average weekly consumption by 1-2 units would lower the number of UK citizens developing dementia linked to drinking after age 45 to by about 15,000 people. Overall costs over time would decline by £280 million ($360 million), and 4,767 QALYs would be gained.

A reduction in salt intake showed the most dramatic change. The authors modeled a policy that would cut average daily intake by 1.68 grams per person, with an accompanying decrease of 1.59 mm Hg in systolic blood pressure. Given the relationship previously found between hypertension and dementia risk, Livingston’s group estimated that more than 43,000 adults would not suffer dementia later, £2.37 billion ($3.04 billion) would be saved in healthcare expenses, and 39,000 QALYs would be gained.

“It is possible that policy makers are hesitant to put these interventions into place given the long lead time before the benefits of cognitive decline could be expected,” the investigators write in their report. “However, given the effect of these interventions on vascular or brain health in general, benefits in terms of other non-communicable diseases would be expected sooner. Our analysis further strengthens the argument for implementation of effective population-level policies as soon as practicably possible.”

“Policy makers should prioritize resources to enable risk reduction to prevent or delay dementia and interventions to improve symptoms and life for people with dementia and their families,” the commission argues.