Eek! Mild Cognitive Impairment?


By Mary Carpenter

SURPRISE” and “startling” were among the responses to last week’s FDA announcement of delayed action on the new Alzheimer disease (AD) drug, donanemab, that combats build-up of amyloid proteins in the brain, according to the New York Times. But reports of the drug trials included two important findings—first, concrete evidence based on participants’ tau protein levels, that “treating people as early as possible in the disease provides a better chance of slowing the symptoms.”

More revelatory was the continued slowing of cognitive decline in participants who stopped taking the drug mid-trial, when amyloid plaques had cleared to a certain extent—and were expected to remain below threshold levels for “nearly four years.” In the same class as donanemab, given by infusion every two weeks, the only other drug that targets mild cognitive impairment (MCI) is lecanemab (Lequembi), requiring weekly infusions. Mild cognitive impairment is greater than that expected for an individual’s age and education level while not interfering with daily activities.

(Makers of the first approved drug in this class, aducanumab (Aduhelm), discontinued sales last year due to “weak evidence for efficacy, serious side effect risks, and a high price point,” according to Very Well Health. Side-effect risks that are also true of donanemab and lecanemab include brain bleeds. And, not approved for MCI, an earlier class of drugs blocks the breakdown of the neurochemical acetylcholine in patients with AD.)

The “high stakes and rocky history of developing treatments” for AD were once again under the spotlight in last week’s decision, notes the NYT. This newer class of drugs may not slow cognitive decline even enough for those with MCI or their families to notice. Also, the research made public the still not-well elucidated roles in AD played by both amyloid and tau proteins—that disrupt neuron cell messaging that results in “widespread loss of brain function as many neurons stop working and eventually die.” 

The cause of MCI can be something reversible—vitamin deficiency, medication side effect, high blood pressure, sleep disorder—but is more often, University of Missouri neuroscientist Andrew Kiselica told the New York Times, “the stage before dementia where there are more thinking problems than we would expect for your age.”

Using additional strategies to keep up with basic activities can be an important clue to cognitive difficulties. Said Kiselica, “They’re remembering their medications or what to pick up with shopping, but they have to use a lot more to-do lists to make sure they’re getting those things done.”

“Telling events” of forgetfulness are another example, according to Johns Hopkins geriatrics specialist Halima Amjad. While everyone may have occasional experiences of forgetting their phone or why they went downstairs, Amjad points to a more serious issue of, “Gosh, I had to call someone because I couldn’t find my car in the parking lot.”

“It’s a subtle condition,” Mayo Clinic AD Research Center Director Ronald Petersen told the Washington Post about MCI. “People can still drive, pay their bills and do their taxes —they just do so less efficiently.” Petersen gives the example of missing a date several times in a week, and “people in your family are starting to worry about you.”

For online self-testing, the Self-Administered Gerocognitive Exam (SAGE) is “the gold standard” for MCI—that can be helpful before making a doctor’s appointment or to bring in for the examining physician, according to the Post. But cognitive testing may produce less accurate results for well-educated people—notably those who have scored high on academic tests—who engage in regular cognitive activities, such as reading, writing, teaching and learning a foreign language.

Risk factors most often linked to age-related impairment include those over which people have some control—notably the degree of social engagement, as well as high blood pressure, high cholesterol and smoking. Also on the list but more challenging to control are diabetes, obesity and depression—as well as traumatic brain injuries—notably, from falling down.

Inflammation is emerging as a primary culprit in most of these conditions—linked to “all known genetic and environmental risk factors for AD,” according to one summary report. As a result, keeping a lid on inflammation-inducing stress ranks high on the list of measures to help prevent or postpone dementia—as do anti-inflammatory medications and diets.

Generally, anti-inflammatory protocols emphasize eating a wide variety of fruits and vegetables, unsaturated fats, minimally refined whole grains and oily fish— and avoiding foods such as fatty cuts of red meat, excess alcohol and refined sugary foods and beverages. Sugar is a primary villain, with evidence that fructose provokes many of the brain changes associated with AD.

Among difficult-to-control items on the risk list are high levels of noise and air pollution—along with back sleeping if linked to disordered sleep and trouble breathing at night. For me, sugar remains the main dementia-related demon, but at least I can count the teaspoons. Social engagement, on the other hand, is trickier—requiring a balance of time spent with other people along with enough alone time so that stress levels remain manageable.

—Mary Carpenter regularly reports on topical subjects in health and medicine.



One thought on “Eek! Mild Cognitive Impairment?

  1. Christy Wise says:

    Excellent article, Mary. Thanks for you thorough and thoughtful research.

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