— Update from Lancet Commission incorporates vision loss, high LDL to risk factors

PHILADELPHIA -- The Lancet Commission on dementia prevention, intervention, and care has expanded the list of modifiable risk factors linked to cognitive decline to 14, after new research conducted since its previous report in 2020.

Vision loss and elevated low-density lipoprotein (LDL) cholesterol have been added to the commission's risk factor list, which previously included 12. This revised 57-page report, led by Gill Livingston, MD, of University College London, was published in The Lancet, and presented at the Alzheimer’s Association International Conference this week.

The 14 identified risk factors include:

• Education
• Hearing loss
• Depression
• Head injuries from sports and cycling
• Physical inactivity
• Smoking
• Hypertension
• Obesity
• Type 2 diabetes
• Alcohol consumption
• Social isolation
• Air pollution
• Vision impairment
• Elevated LDL

Addressing these issues comprehensively — by improving education access, controlling obesity, enforcing helmet rules for youth, mitigating air pollution, and more — could reduce global dementia risk by up to 45%, according to the commission’s review of approximately 600 research papers.

Specifically, high LDL accounts for around 7% of dementia risk, making it one of the most significant contributors. Hearing loss also represents 7% of the risk, while both social isolation and low educational attainment account for 5%. Other factors contribute 3% or lower, with vision loss responsible for just 2% of risk.

The commission also reviewed other potential risk factors linked to dementia, including diet, sleep deprivation, and mental health disorders like bipolar disorder or psychosis. However, researchers concluded the evidence was insufficient to establish definitive risk percentages for these factors. Additionally, there’s not enough proof that interventions for these conditions will directly reduce the risk of dementia.

The report also touched upon direct dementia interventions, such as diagnostic tests, symptomatic treatments like anticholinesterase inhibitors, and anti-amyloid drugs. The discussion was qualitative rather than quantitative, and the commission viewed current symptomatic treatments positively, noting that they offer "short-term, modest positive effects," while stopping them results in worse long-term outcomes.

However, the commission had reservations about anti-amyloid therapies, such as donanemab (Kisunla) and lecanemab (Leqembi). “The effects of these [anti-amyloid] drugs remain modest,” the authors noted, adding that their broad adoption may be slow or even impossible in some healthcare systems due to the resources needed for early biomarker diagnostics, drug administration monitoring, and drug availability. (Reflecting these concerns, alongside safety risks, the European Medicines Agency recently declined to approve lecanemab for use in Europe.)

Livingston and many of the same researchers also contributed to a separate publication in *The Lancet Healthy Longevity*, focusing on the cost-effectiveness of interventions to address six risk factors in England. These include alcohol consumption, dietary salt and sugar intake, automotive pollution, smoking, and head injuries in youth. They explored interventions already tested in specific scenarios: raising taxes on alcohol and tobacco, reducing salt and sugar content in commercial food products, restricting automobile access in certain areas, and mandating helmet use for cyclists. Using economic modeling, they estimated the cost-effectiveness and projected quality-adjusted life years (QALYs) gained if these interventions were applied in England.

For example, increasing alcohol prices by a margin that reduced weekly intake by 1-2 units in Scotland would prevent about 15,000 people aged 45 and older in Britain from developing alcohol-related dementia in the future. This would ultimately cut costs by £280 million ($360 million), while gaining 4,767 QALYs.

The greatest projected benefit came from salt reduction. A policy aiming to reduce daily salt intake by 1.68 grams per person (with a corresponding 1.59 mm Hg drop in systolic blood pressure) could prevent over 43,000 cases of dementia linked to hypertension. The cost savings would reach £2.37 billion ($3.04 billion) and result in more than 39,000 QALYs gained.

While recognizing the political challenges, the researchers acknowledged, “[i]t is possible that policy makers might hesitate to implement these measures given the long timeframe before the cognitive benefits become apparent.”

“However, since these interventions also improve vascular and brain health generally, outcomes related to other non-communicable diseases can be expected sooner.” They emphasized that their findings “further bolster the case for implementing effective, population-wide policies as soon as is feasible.”

The Lancet Commission similarly urged governments and public health bodies to “prioritize resource allocation for risk reduction strategies that can prevent or delay dementia, as well as to improve care and quality of life for those living with the disease and their families.”

Disclosures

The Commission’s work was funded by the Alzheimer’s Society, the Economic and Social Research Council, and Alzheimer’s Research UK. Authors disclosed several governmental and foundation grants, plus a range of industry affiliations.

Funding for the England model study was provided by the UK National Institute for Health and Care Research. Livingston reported receiving support from government and nonprofit organizations in the UK and Norway. Other researchers disclosed no significant financial interests.

Primary Source

The Lancet

Source Reference: Livingston G, et al. "Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission" Lancet 2024; DOI: 10.1016/S0140-6736(24)01296-0.

Secondary Source

The Lancet Healthy Longevity

Source Reference: Mukadam N, et al. "Benefits of population-level interventions for dementia risk factors: an economic modelling study for England" Lancet Healthy Longev 2024; DOI: 10.1016/S2666-7568(24)00117-X.