Natural treatments for mental and cognitive decline in older adults

• PRINCIPAL PROPOSED NATURAL TREATMENTS: Acetyl-L-carnitine, Ginkgo biloba, huperzine A, phosphatidylserine, vinpocetine
• OTHER PROPOSED NATURAL TREATMENTS: Aromatherapy, carnosine, citrulline, choline or phosphatidylcholine, fish oil, treating high homocysteine, dehydroepiandrosterone, lemon balm, N-acetylcysteine, sage, vitamin E

DEFINITION: Treatment of mental and cognitive decline in older adults.

Introduction

Alzheimer’s disease is the most common cause of severe mental deterioration (dementia) in older adults. It is estimated that 30 to 50 percent of people over the age of eighty-five have this condition, and 10 percent of people over the age of sixty-five have Alzheimer’s disease. Microscopic examination of the brains of people who have died of Alzheimer’s shows loss of cells in the thinking part of the brain, particularly cells that release a chemical called acetylcholine.

Alzheimer’s begins with subtle symptoms, such as loss of memory for names and recent events. It progresses from difficulty learning new information to a few eccentric behaviors to depression, loss of spontaneity, and anxiety. Over the course of the disease, the person gradually loses the ability to carry out everyday life activities. Disorientation, asking questions repeatedly, and an inability to recognize friends are characteristics of moderately severe Alzheimer’s. Eventually, virtually all mental functions fail.

Alzheimer’s disease causes the volume of the brain to shrink substantially.

Similar symptoms may be caused by conditions other than Alzheimer’s disease, such as multiple small strokescalled multi-infarct or vascular dementiasevere alcoholism, and certain rarer causes. It is critical to begin with an examination to discover what is causing the symptoms of mental decline. Various treatable conditions, such as depression, can mimic the symptoms of dementia.

Several drugs have shown at least modest benefit for Alzheimer’s disease or non-Alzheimer’s dementia: galantamine (Reminyl), rivastigmine (Exelon), donepezil (Aricept), galantamine (Razadyne), and tacrine (Cognex). These medications usually produce a modest improvement in mild to moderate Alzheimer’s disease by increasing the duration of action of acetylcholine. However, they can sometimes cause severe side effects because of the exaggeration of acetylcholine’s action in other parts of the body. These medications do not reverse the disease but help slow the progression and improve the individual's quality of life.

Principal Proposed Natural Treatments

There are two natural treatments for Alzheimer’s disease with significant scientific evidence behind them: Ginkgo biloba and phosphatidylserine. Huperzine A and vinpocetine, while more like drugs than natural remedies, may also improve mental function in people with dementia. Acetyl-L-carnitine was once considered a promising option for this condition, but evidence suggests it does not work.

Ginkgo biloba. The best-established herbal treatment for Alzheimer’s disease is the herb Ginkgo biloba. Numerous high-quality, double-blind, placebo-controlled studies indicate that ginkgo is effective for treating various forms of dementia. One of the largest studies was a 1997 trial in the United States that enrolled more than three hundred people with Alzheimer’s disease or non-Alzheimer’s dementia. Participants were given 40 milligrams (mg) of either ginkgo extract or a placebo three times daily for fifty-two weeks. The results showed significant but not entirely consistent improvements in the treated group.

Another study published in 2007 followed four hundred people for twenty-two weeks and used twice the dose of ginkgo employed in the foregoing study. The results of this trial indicated that ginkgo was significantly superior to placebo. The areas in which ginkgo showed the most marked superiority compared with placebo included “apathy/indifference, anxiety, irritability/lability, depression/dysphoria and sleep/nighttime behavior.”

One large study of ginkgo extract made headlines for concluding that ginkgo is ineffective. This twenty-four-week, double-blind, placebo-controlled study of 214 participants with either mild to moderate dementia or ordinary age-associated memory loss found no effect with ginkgo extract at a dose of 240 or 160 mg daily. However, this study has been sharply criticized for a number of serious flaws in its design. In another community-based study among 176 older persons with early-stage dementia, researchers found no beneficial effect for 120 mg of ginkgo extract given daily for six months.

The ability of ginkgo to prevent or delay a decline in cognitive function is less clear. In a placebo-controlled trial of 118 cognitively intact adults age eighty-five years or older, ginkgo extract effectively slowed the decline in memory function during a forty-two-month period. The researchers also reported a higher incidence of stroke in the group that took ginkgo, a finding that requires more investigation.

In a 2009 review of thirty-six randomized trials involving 4,423 persons with declining mental function (including dementia), researchers concluded that ginkgo appears safe but added that there is inconsistent evidence of its effectiveness. This finding was echoed in a mid-2020s analysis of research, but overall, findings continued to be mixed.

Phosphatidylserine. Phosphatidylserine is one of the many substances involved in the structure and maintenance of cell membranes. Double-blind studies involving more than one thousand people suggest that phosphatidylserine is an effective treatment for Alzheimer’s disease and other forms of dementia.

The largest of these studies followed 494 persons of an advanced age in northeastern Italy for six months. All had moderate to severe mental decline, as measured by standard tests. Treatment consisted of 300 mg daily of either phosphatidylserine or placebo. The group that took phosphatidylserine did significantly better in both behavior and mental function than the placebo group. Symptoms of depression also improved.

These results agree with those of numerous smaller double-blind studies involving more than five hundred people with Alzheimer’s and other types of age-related dementia. However, the form of phosphatidylserine available as a supplement has altered since the studies described above were performed, and the available form may not be equivalent. A 2022 meta-analysis found positive results for patient memory and cognitive function, but many of the studies were small, lacked a placebo group, or had other shortcomings that made their results unreliable. Additionally, dosages ranged from 80 to 500 mg per day between studies.

Huperzine A. Huperzine A is a chemical derived from a particular type of club moss (Huperzia serrata). Like caffeine and cocaine, huperzine A is a medicinally active, plant-derived chemical that belongs to the class known as alkaloids. This substance is more a drug than an herb, but it is sold over the counter as a dietary supplement for memory loss and mental impairment.

According to three Chinese double-blind trials enrolling more than 450 people, the use of huperzine A can significantly improve symptoms of Alzheimer’s disease and other forms of dementia. However, one double-blind trial failed to find evidence of benefit, but it was a relatively small study. In a review of six randomized, controlled trials, researchers concluded that, on balance, huperzine A is probably of some benefit in Alzheimer’s disease, but the variable quality of these studies weakens this conclusion.

Vinpocetine. Vinpocetine is a chemical derived from vincamine, a constituent found in the leaves of common periwinkle (Vinca minor) and in the seeds of various African plants. It is used as a treatment for memory loss and mental impairment.

Developed in Hungary, vinpocetine is sold in Europe as a drug called Cavinton. It is available as a dietary supplement in the United States, although the substance probably does not fit that category. Vinpocetine does not exist to any significant extent in nature. Producing it requires significant chemical work performed in the laboratory.

Several double-blind studies have evaluated vinpocetine for the treatment of Alzheimer’s disease and related conditions. Most of these studies had significant flaws in design and reporting. A review of the literature found three studies of acceptable quality, enrolling 583 people. Perhaps the best of these was a sixteen-week, double-blind, placebo-controlled trial of 203 people with mild to moderate dementia that found significant benefit in the treated group. However, even this trial had several technical limitations, and the authors of the review concluded that vinpocetine cannot be regarded as a proven treatment.

Acetyl-L-carnitine. Carnitine is a vitamin-like substance that is often used for angina, congestive heart failure, and other heart conditions. A special form of carnitine, acetyl-L-carnitine, has been extensively tested for the treatment of dementiadouble-blind or single-blind studies involving more than fourteen hundred people have been reported.

While early studies found evidence of modest benefit, two large and well-designed studies failed to find acetyl-L-carnitine effective. The first of these was a double-blind, placebo-controlled trial that enrolled 431 people for one year. Overall, acetyl-L-carnitine proved no better than placebo. However, because a close look at the data indicated that the supplement might help people who develop Alzheimer’s disease at an unusually young age, researchers performed a follow-up trial. This one-year, double-blind, placebo-controlled trial evaluated acetyl-L-carnitine in 229 persons with early-onset Alzheimer’s. No benefits were seen here either.

One review of the literature interpreted the cumulative results to mean that acetyl-L-carnitine may be mildly helpful for mild Alzheimer’s disease. However, another review concluded that if acetyl-L-carnitine does offer benefits for any form of Alzheimer’s disease, they are too minor to make much of a practical difference.

Other Proposed Natural Treatments

Two small double-blind studies performed by a single research group found evidence that the herbs sage and lemon balm can improve cognitive function in people with mild to moderate Alzheimer’s disease.

One study found that vitamin E (dl-alpha-tocopherol) may slow the progression of Alzheimer’s disease, but another study did not. Another large study failed to find that the use of vitamin E reduced the risk of general mental decline (whether caused by Alzheimer’s or not) in women older than age sixty-five years. Preliminary evidence suggests that N-acetylcysteine (NAC) might also be helpful for slowing the progression of Alzheimer’s disease. While some studies supported the use of vitamin E, others concluded it should not be used in individuals with cognitive decline.

Lavender oil used purely as aromatherapy (treatment involving inhaling essential oils) has been advocated for reducing agitation in people with dementia. However, people with dementia tend to lose their sense of smell, making this approach unlikely to work. Topical use of essential oil of the herb lemon balm has also shown promise for reducing agitation in people with Alzheimer’s disease. The researchers who tested it considered their method aromatherapy because the fragrance wafts up from the skin, but essential oils are also absorbed through the skinthis mechanism of action seems more plausible. Oral use of lemon balm extract has also shown promise. Overall, research does not support the use of aromatherapy or essential oils for individuals with dementia. However, aromatherapy is a low-risk, low-cost therapy that may help relax some patients.

Drugs used for Alzheimer’s disease affect levels of acetylcholine in the body. The body makes acetylcholine out of the nutrient choline. On this basis, supplements containing choline or the related substance phosphatidylcholine have been proposed for the treatment of Alzheimer’s disease, but the results of studies have not been positive. One special form of choline, however, has shown more promise. In a six-month double-blind study of 261 people with Alzheimer’s disease, using Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) at a dose of 400 mg three times daily significantly improved cognitive function compared with placebo. A later literature review reported similarly positive findings in seven studies. In some cases, donepezil was combined with Choline alphoscerate, which appeared to improve outcomes. Colistrinin, a substance derived from colostrum, has shown some promise for the treatment of Alzheimer’s.

Bee pollen, carnosine, citrulline, 2-dimethylaminoethanol, inositol, magnesium, pregnenolone, vitamin B₁, and zinc have also been suggested as treatments for Alzheimer’s disease. However, there is no reliable scientific evidence to support their use. Elevated blood levels of the substance homocysteine have been suggested as a contributor to Alzheimer’s disease and multi-infarct dementia. However, a double-blind, placebo-controlled study failed to find that homocysteine-lowering treatment using B vitamins was helpful for multi-infarct dementia. Similarly, two studies failed to find benefits in people with Alzheimer’s disease. In another study, a mixture of B vitamins did not improve the quality of life in people with mild cognitive impairment of various causes. Early reports suggested that declining levels of the hormone dehydroepiandrosterone (DHEA) cause impaired mental function in older adults. On this basis, DHEA has been promoted as a cognition-enhancing supplement. However, the one double-blind study that tested DHEA for Alzheimer’s disease found little to no benefit. Studies of fish oil have failed to find it helpful for Alzheimer’s disease, whether for delaying its onset, slowing its progression, or improving its symptoms.

In a sizable Danish trial, researchers investigated the effects of melatonin and light therapy (bright light exposure during daylight hours) on mood, sleep, and cognitive decline in older adults, most of whom had dementia. They found that melatonin 2.5 mg, given nightly for an average of fifteen months, slightly improved the quality of sleep, but it worsened mood. Melatonin apparently had no significant effect on cognition. Light therapy alone slightly decreased cognitive and functional decline and improved mood. Combining melatonin with light therapy improved mood and quality of sleep.

In terms of dietary intake to counter the effects of Alzheimer’s Disease, in the 2020s, many marketing campaigns have touted various herbal and dietary supplements as treatments for Alzheimer’s Disease. However, users must note that as supplements, the US Food and Drug Administration (FDA) does not regulate such claims. It falls to consumers to establish the accuracy of these promotions and whether they are safe to combine with other medications. It should also be understood that scientific research has not identified a food, beverage, or other substance that has shown to be an effective cure, preventative, or treatment for Alzheimer’s Disease. In 2023, the FDA approved lecanemab (Leqembi), an antibody administered intravenously every two weeks. This is a medicine believed to slow the progress of Alzheimer’s Disease for those with mild conditions and cognitive impairments.

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