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The rising tide of dementia and the need for nondrug therapies

senior man in a wheelchair interacting with a small dog held by a care facility staff member

The human and financial cost of Alzheimer’s disease is devastating. More that 55 million people are living with Alzheimer’s disease and other causes of dementia, rising to 78 million by 2030 and 139 million by 2050. In the United States alone, the Alzheimer’s Association estimated that in 2020, more than 11 million unpaid caregivers provided 15.3 billion hours of assistance (valued at $256.7 billion) to 6.2 million people with dementia. That estimate does not include the $51.2 billion in Medicaid payments for Americans ages 65 and older living with dementia.

Pharmacological solutions to slow down Alzheimer’s disease

For years, most Alzheimer’s clinicians, researchers, and advocacy groups have pinned their hopes on a pharmaceutical solution to this crisis, yet there has been failure after failure. Last year, amid considerable professional debate, the FDA approved the first medication thought to be able to slow the accumulation of Alzheimer’s disease pathology in the brain. The theory, as yet unproven, is that if such a drug is given early enough — before there are any symptoms — the disease progression will be so gradual that people will be able to live out their lives without developing disabling dementia.

A looming crisis

Although this hoped-for trajectory is logical and laudable, the immediate effect may be costly. The vast majority of new medications being developed for Alzheimer’s disease — including the one the FDA approved — are being evaluated in people who already have symptoms, such as memory loss. These new disease-modifying drugs will therefore first be used in millions of individuals with mild Alzheimer’s symptoms. Because these drugs slow down (but not stop) the accumulation of pathology, individuals with symptomatic Alzheimer’s disease will continue to progress, and — if the therapies are successful — they will progress more slowly. Instead of the mild stage of dementia lasting about three years, it might last four, five, or six years. Instead of the moderate stage lasting about four years, it might last five, six, or seven years. This means that, for the foreseeable future, disease-modifying drugs will not decrease the numbers of individuals living with dementia — it will hugely increase them.

For this reason, it is critical that the US and other countries invest in not only pharmacological but also nonpharmacological treatments for Alzheimer’s disease and other dementias. Although many strategies have been developed to improve memory in those patients with mild memory symptoms, few, if any, of these interventions have undergone large clinical trials to prove (or disprove) their efficacy.

The potential benefit of nonpharmacologic memory-boosting strategies in the mild stages

One study from a group of Boston researchers examined 32 individuals with mild memory problems, half with mild cognitive impairment and half with mild Alzheimer’s disease dementia. They found that both groups improved their memory by simply thinking about the following question when learning new information: “What is one unique characteristic of this item or personal experience that differentiates it from others?” Another study by Boston researchers found that 19 individuals with mild cognitive impairment could improve their ability to remember items at a virtual supermarket by simply thinking systematically about whether items were already in their cupboard before putting them in their shopping cart. Larger studies are needed, however, to determine if such memory strategies are generalizable.

Music, pets, robots, and the environment in the moderate to severe stages

Similarly, there are many nonpharmacological treatments that appear to provide comfort and reduce agitation in individuals with moderate to severe dementia, but larger and more rigorous studies are needed to prove or disprove their efficacy, and thereby promote more widespread utilization.

  • A group of Portuguese clinicians and researchers reviewed more than 100 studies evaluating music-based interventions for people with dementia who had agitation or other behavioral and psychological symptoms of dementia, finding that the vast majority were efficacious with little or no side effects.
  • A team of neurologists from Florida reviewed the effects of dog therapy and ownership, finding that both were safe and effective approaches to treat chronic and progressive neurological disorders.
  • Other researchers found reductions in anxiety and psychoactive medication use when robot pets were given to individuals with dementia.
  • A review of the built environment (the architecture of the home or facility) concluded that “specific design interventions are beneficial to the outcomes of people with dementia.”

Education for families

Educating families and other caregivers about how to manage the different stages and facets of dementia is also critical. One pilot study by Brazilian clinicians invited caregivers to participate in educational sessions and found a high rate of program satisfaction. Unfortunately, these types of caregiver education interventions are rarely studied in large clinical trials.

Enormous potential savings

If strategies in the mild stages prove effective enough to save just one hour each week of a caregiver’s time for the roughly two million people in the US with mild dementia, it could save 104 million hours valued at $1.7 billion each year. That extra hour might, for example, allow a “sandwiched caregiver” to help their child with homework while their parent with mild dementia takes medications or pays bills independently.

If nonpharmacologic interventions in the moderate to severe stages saved just one month of nursing home care for the roughly four million people with moderate to severe dementia in the US, it would save more than $31 billion dollars (based on a semi-private nursing home room costing $93,075 per year). And that financial savings is in addition to the social and emotional benefit to individuals with Alzheimer’s disease and their families.

New models of reimbursement

Finally, once nonpharmacological treatments have been proven efficacious, new models of reimbursement will be needed to pay for their implementation, as traditional insurance payments are geared toward medications. The only way the US — and the world — will be able to cope with the rising numbers of people with dementia will be for nonpharmacological approaches to be used along with pharmacological therapies.

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Can flavonoids help fend off forgetfulness?


The foundation of a healthy diet is a vibrant rainbow of fruits and vegetables, like rosy red strawberries, dark green spinach leaves, or sunny yellow peppers. Their colors often come from flavonoids, powerful plant chemicals (phytochemicals) that appear to contribute to many aspects of health. And now a large Harvard study published online in Neurology in July suggests that flavonoids may also play a role in protecting cognition.

The investigation

Scientists evaluated the health data and self-reported diet information of more than 77,000 middle-aged men and women, collected over 20 years.

The information included how often participants ate many types of flavonoid-rich foods and whether participants reported cognition changes in their 70s, such as difficulty

  • remembering recent events or a short list of items
  • remembering things from one second to the next
  • understanding instructions
  • following a group conversation or TV plot
  • finding their way around familiar streets.

Researchers then calculated participants’ intake of six classes of flavonoids:

  • flavonols (such as quercetin in onions and kale)
  • flavones (such as luteolin in green chile peppers and celery)
  • flavanones (such as naringenin in grapefruit and oranges)
  • flavan-3-ol monomers (such as catechins in red wine and strawberries)
  • anthocyanins (such as cyanidin in blackberries and red cabbage)
  • polymers (such as theaflavins in black tea).

What the study found

After accounting for factors that could have affected cognition (such as age, weight, physical activity, alcohol intake, depression, and non-flavonoid nutrient intake), scientists found that people with the highest daily flavonoid intakes were 19% less likely to report trouble with memory and thinking, compared to people with the lowest daily flavonoid intakes.

"Our results are exciting because they show that eating foods high in flavonoids could help prevent or slow down decline in memory and other cognitive processes in late life," says Dr. Walter Willett, one of the study’s authors and a professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health.

"We noticed that earlier consumption of flavonoid-rich foods seemed to improve the protective effect on the brain. But even participants who began eating more flavonoids later in life saw benefits," says Dr. Tian-Shin Yeh, the study’s lead author and a postdoctoral research fellow in the Harvard-Oxford Program in Epidemiology and the department of nutrition at the Harvard T.H. Chan School of Public Health.

The study was only observational, relying on what people remembered about their diets and noticed about cognition, and didn’t prove conclusively that flavonoid intake kept people sharp in older age. But smaller or shorter-term studies have also found a link between flavonoids and cognitive health benefits.

Flavonoid superstars

Some flavonoids in particular appeared to have protective effects on the brain:

  • Flavones were associated with a 38% lower risk for self-reported cognitive decline.
  • Flavanones had a 36% lower risk for self-reported cognitive decline
  • Anthocyanins had a 24% lower risk for self-reported cognitive decline.

Click here (note: automatic download) for a USDA list of top choices for these three types of flavonoids.

The fruits and vegetables in the study most associated with beneficial cognitive effects, listed from strongest to weakest, were:

  • Brussels sprouts
  • strawberries
  • cauliflower
  • raw spinach
  • yams/sweet potatoes
  • blueberries
  • yellow/orange winter squash
  • cooked spinach
  • cooked carrots
  • peaches/apricots/plums
  • cantaloupe
  • tomato juice
  • applesauce
  • green/red/yellow peppers
  • broccoli
  • cabbage
  • tomato sauce
  • romaine lettuce
  • tomatoes
  • grapefruit
  • celery
  • beets
  • iceberg lettuce
  • baked/boiled/mashed potatoes
  • orange juice
  • raw carrots
  • apples/pears
  • grapefruit juice
  • bananas
  • oranges
  • onions
  • apple juice/cider
  • tea
  • white wine
  • grapes/raisins
  • red wine.

What’s the magic in flavonoids?

We don’t know for sure why flavonoids might play a role in protecting cognition. But we do know that flavonoids are powerful antioxidants, which may fight brain inflammation and the accumulation of amyloid — a hallmark of Alzheimer’s disease.

Antioxidants may also play a part in

  • keeping the blood vessels healthy (which keeps blood flowing to the brain)
  • increasing the production of brain-derived neurotrophic factors, chemicals that repair brain cells, strengthen their connections, promote new brain cell growth, and enlarge the size of your hippocampus (a part of the brain involved in the storage and retrieval of memories).

Plus, we know that flavonoids are associated with fighting inflammation and tumor growth, and in lowering blood pressure.

Setting simple flavonoid goals

With so many potential flavonoid benefits, you may be wondering what kind of levels you should aim for in your diet. In the study, flavonoid intakes ranged from low — about 150 milligrams (mg) per day — to high — about 620 mg per day.

But tracking flavonoids is complicated. They vary greatly depending on the food. For example, half a cup of blueberries contains about 165 mg of anthocyanins; half a cup of peppers contains about 5 mg of flavones. And many fruits and vegetables contain several types of flavonoids, along with many other phytochemicals.

So don’t stress about it. Just eat a diet with a wide variety of fruits and vegetables — the sooner you start, the better. Try to reach the five-a-day fruit and vegetable goal (recent evidence suggests that the most effective combination is two servings of fruits plus three servings of vegetables per day).

Then, as you enjoy foods like strawberries, blueberries, peppers, celery, apples, bananas, oranges, and grapefruit, remember they’re not only tasty and good for general health, but potentially helpful for your brain, too.

"It’s been called ‘eating the rainbow,’ and can lead to a healthier, more delicious diet; and it’s another reason why we should ensure that everyone has access to fresh fruits and vegetables," says Dr. Deborah Blacker, a study co-author and professor and deputy chair of epidemiology at the Harvard T.H. Chan School of Public Health.