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REPORTS OF new drugs, new tests and new do’s and don’ts for combating Alzheimer’s disease (AD) via both prevention and treatment keep raising new hopes. Of more than five million Americans age 65 and older living with Alzheimer’s dementia in 2020, two-thirds are women.
The experimental drug aducanumab, which would be the first drug approved to slow deterioration in brain function, is currently under review by the FDA, with a final decision expected by March, although its advisory committee in early November advised against approval.
And about to be widely available is a blood test that assesses beta-amyloid plaques, considered early signs of AD pathology, in the brains of people experiencing new memory loss, according to the Alzheimer’s Drug Discovery Foundation. The early-detection test could help individuals begin exploring treatment options and provide a “reliable, accessible and affordable biomarker” for AD research.
The test’s developer, C2N Diagnostics, is also working on tests for other AD markers, such as tau proteins that form tangles in the brain—possibly the best predictor of future brain atrophy, according to PET (positron emission tomography) scans. PET scans, along with spinal fluid tests, are current gold standards for AD assessment—but are expensive, not covered by Medicare, and in the latter case, invasive.
Under do’s and don’ts for forestalling AD is “the Beers List” —drugs determined by Beers criteria (developed by Dr. M.H. Beers in 1991) to be risky for older adults—published by the American Geriatrics Society. In two large population studies, both benzodiazepines and anticholinergics, including medications for allergy, depression, high blood pressure and incontinence, raised the risk of dementia in people who used them for longer than a few months. While these drugs have side effects that include “confusion, clouded thinking and memory lapses,” studies have not yet proved that the drugs cause dementia, cautions the Harvard Health Letter. One reason: acetylcholine, the neurotransmitter in the brain that is both reduced by these drugs and involved in learning and the formation of new memories, declines naturally with age.
Nonetheless, researchers are eyeing the sage plant, known to affect amyloid buildup as well as cholinergic activity in the brain. In short-term studies with AD patients, sage supplements have provided some cognitive enhancement and brain protection. But researchers caution about the need for longer term studies as well as confirmation of safety and better information about which sage species and quality of extracts work best.
“Brain benefits” may also come from higher brain levels of omega-3 fatty acids, based on research by Costa Mesa California neuropsychiatrist Daniel Amen. Using SPECT (single photon emission computed tomography) scans—which can assess blood flow and activity in 128 specific regions of the brain—on a random group of 166 patients, researchers found greater blood flow in areas concerned with memory and cognition in those patients with higher blood levels of omega-3 fats.
Vascular disease in the heart and blood vessels is to date the best-documented target of omega-3s in the body, as well as appearing to be a key cause of cognitive decline. Also, cerebrovascular risk factors (hypertension, atherosclerosis, and diabetes) as well as aerobic exercise, Mediterranean diet, and cognitive and social engagement are keystones of the “Bredesen protocol,” named by California neurologist Dale Bredesen, which has been touted as the first approach to reverse declining brain function in AD patients.
Bredesen’s protocol, outlined in his two “End of Alzheimer’s” books, is available for patients— including assessments, tests and expert advice—for package fees starting around $1,000. However, an editorial earlier this year found “major flaws” and “second-rate science” in Bredesen’s research, writes cognitive neurologist Joanna Hellmuth of the UCSF Memory and Aging Center in Lancet Neurology. Hellmuth points out that these keystone lifestyle interventions are “largely cost-free” and considered standard of care in dementia clinics.
Inflammation, one focus of Bredesen’s protocol, is associated with “all known genetic and environmental risk factors for AD,” according to a review published in in Frontiers in Medicine. Among psychedelic drugs, both psilocybin and LSD have shown “potent anti-inflammation properties” that may be “overwhelmingly targeted to brain tissue.” In both “micro-doses” and large doses, the brain effects of these drugs, including induced plasticity and modification of connectivity between regions, suggest their benefits as a “strategy for neuroprotection and cognitive enhancement in [early] prodromal AD.”
But for many experts, aducanumab is the most significant recent development—in part because it would be the first new AD drug approved in 17 years and one of the few drugs approved in 40-plus years of AD research. Disagreement about whether the FDA should approve the drug focuses on the degree of improvement achieved—which is especially important considering the drug’s high cost.
Aducanumab targets one pathology of AD seen in patients not yet diagnosed with dementia but who have “mild cognitive impairment (MCI): changes in an individual’s cognitive abilities that, “while noticeable and often annoying, are not disabling,” writes neurologist Jason Karlawish at the University of Pennsylvania’s Penn Memory Center.
Approximately 40% of patients over age 65 diagnosed with MCI develop dementia within three years. In trials of aducanumab conducted by the drug’s developer, Biogen, 80% of participants with MCI also had PET scans showing elevated amounts of amyloid plaque in their brains.
While amyloid buildup is often seen in the brains of patients with AD, it is still not clearly the cause of AD dementia, which is linked most strongly to age and genetics. For this reason, Karlawish suggests that renaming might be in order—giving those with abnormal amyloid the option of saying they have amyloidosis. “A drug that targets a pathology targets stigma,” he writes, by offering “some explanation for what’s wrong, the hope of treatment, and a means to rethink and even rename a disease.”
For those who might be vulnerable to AD, a host of other don’ts include sugar and noise. According to one theory, fructose provokes many of the brain changes associated with AD. As for noise, a study on aging—with more than 5,000 participants age 65 and older, and almost 40% with MCI and 11% with AD—linked each 10-decibel (db) increase in community noise level with a 36% higher likelihood of MCI and a 29% increased risk for AD.
Possible causes for the negative effects of loud noise on the brain include increased heart rate, constriction of blood vessels and sleep loss—all associated with increased risk for dementia. Among hard-to-control community noises, the leaf blower ranks high. For anyone standing next to a leaf blower, its sound can measure over 100 decibels—compared to closer to 80 dbs at 50 feet, and compared to human speech at about 60 dbs.
The effects of noise are based on levels of both db loudness and perceived annoyance—with loud sounds made by paper, for example, more annoying than other sounds at the same db level. Thus, yoga teachers and others advise focusing on body and breath to resist being annoyed by sounds that cannot be controlled. Otherwise, the best advice: In the presence of loud noises, keep your distance.
—Mary Carpenter
Mary Carpenter regularly reports on topical issues in health and medicine.
