Verified by 
Key points
- Billions of dollars have been invested to develop drugs that rid the brain of amyloid.
- Some researchers are shifting to a different culprit, excess inflammation.
- Boosting exercise and eating a healthy diet can delay the onset of dementia and its progression.
Over a century ago, German psychiatrist Alois Alzheimer described a disease that was gradually robbing people of their minds and independence and now afflicts nearly 11 percent of people over age 65. Alzheimer autopsied brains of deceased dementia patients, which revealed the hallmarks of the disease—amyloid plaques and tau tangles—proteins that amass in the areas of the brain controlling memory, thinking, and behavior.
But after decades of research and the investment of billions of dollars to develop drugs to rid the brain of amyloid, we still don’t have a solution. In 2021, the FDA granted accelerated approval of the intravenous anti-amyloid medication aducanumab, but this was at the objection of the agency’s own advisors, who raised doubts about the drug’s effectiveness. And with highly restricted insurance coverage, very few patients receive the medicine.
More recently, the FDA accelerated the approval of another anti-amyloid drug, lecanemab. Unfortunately, questions remain about its effectiveness and safety. Compared with the older and less-expensive anti-Alzheimer’s drug donepezil, lecanemab’s cognitive effects over 18 months also are modest, with a 27 percent lessening of decline (compared with 29 percent for donepezil). However, the difference in benefits is imperceptible to patients and families. Moreover, after a year of treatment, donepezil delays the progression of mild cognitive impairment to dementia, while lecanemab does not. Unfortunately, anti-amyloid drugs like lecanemab can cause such side effects as potentially lethal brain swelling as well as accelerated brain shrinkage associated with disease progression. More recently, a press release announced similar levels of modest clinical effects and potential side effects for another anti-amyloid drug, donanemab.
The good news? Some researchers are shifting their gaze to a different culprit, excess inflammation. We already know that chronic inflammation is associated with many diseases including diabetes, cancer, arthritis, heart disease, and Crohn's disease. Usually, an inflammatory response helps our bodies fight infection and repair injuries, but too much inflammation can damage cells, including brain cells.
This research builds on several scientific discoveries. Selective autopsy stains have shown evidence of inflammation in amyloid plaques, as demonstrated by damaged microglia, the brain’s trash collector immune cells that normally remove dying neurons and prune synapses (nerve cell junctions), and cytokines, immune proteins that alter inflammation.
Epidemiological studies indicate that the use of anti-inflammatory arthritis drugs reduces the risk of developing Alzheimer’s disease. In the Baltimore Longitudinal Study, volunteers taking common anti-inflammatory drugs like ibuprofen or naproxen for two or more years had a 60 percent reduction in their Alzheimer’s risk.
Unfortunately, these medicines have serious side effects and can actually worsen cognition in people with advanced brain aging. Although my research team found that the anti-inflammatory drug celecoxib improved cognition and affected regional brain metabolism in non-demented people with mild age-associated memory decline, the study sample was small, and large-scale clinical trials of anti-inflammatory drugs have not panned out. Besides, chronic use of such drugs poses significant risks of stomach ulcers, heart attacks, and strokes, particularly in older adults.
In my studies over the years, I have been searching for safer methods to reduce excess inflammation. Curcumin is an active component of the spice turmeric and a key ingredient in curry. Laboratory studies indicate that curcumin has the potential to reduce inflammation and combat tissue-damaging oxidative stress associated with pollution, smoking, other environmental exposures, and aging. My UCLA group’s double-blind, placebo-controlled study showed that daily consumption of a readily absorbed form of curcumin significantly improved memory and attention compared to placebo, and it had very few side effects. Different research groups are now initiating a multi-site replication study to confirm these findings in a much larger group of middle-aged and older adults with mild memory complaints.
There’s another advantage to shifting our focus to inflammation: we can gain more control over our brain health because we have some ability to regulate inflammation.
Older age, obesity, consumption of unhealthy fats and processed sugars, smoking, sleep problems, stress, and lack of exercise all heighten inflammation, and mitigating these risk factors delays cognitive decline. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, a two-year, randomized controlled trial of thousands of older adults, showed that lifestyle interventions like boosting exercise and a healthy diet can delay the onset of dementia and its progression.
When I evaluate patients with age-related cognitive complaints, I routinely review their lifestyle habits and help them to reduce stress, eat healthily, and exercise regularly. But many patients have a hard time changing their habits and ask, “Doc, don’t you just have a memory pill I can take?” A bioavailable form of curcumin may offer a safe, alternative to lowering inflammation and protecting brain health.
Given the modest benefits of anti-amyloid drugs and their extensive side effects, I hesitate to prescribe them. However, I have no qualms about recommending lifestyle-habit adjustments shown to reduce brain inflammation. Amyloid plaques may still be part of the problem, but it’s time we accelerate research on how to reduce brain inflammation.
