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Source: Kindel Media/Pexels

When I co-invented the first PET (positron emission tomography) scan to visualize brain amyloid and tau—the physical evidence of Alzheimer’s disease—I did not foresee the distressing mental impact these test results could have on the psyche of people who received them and had just mild memory issues. I anticipate that similar anxieties will emerge with the new blood test that can precisely diagnose Alzheimer’s disease.

Although the presence of amyloid raises one’s risk for Alzheimer’s, it does not guarantee they will get it—in fact, they may never get it. Receiving such scans or blood test results can lead to increased anxiety, as well as the unfounded perception that one is rapidly losing their ability to think, remember, and enjoy life.

Before a person develops Alzheimer’s dementia (the cognitive decline that makes them dependent on others for care), they first transition from normal age-related forgetfulness to mild cognitive impairment (MCI), a more challenging memory issue that does not disrupt independence but increases the risk for developing dementia. More people are getting these scans and will be getting these blood tests because the presence of brain amyloid is required to receive the recently FDA-approved anti-amyloid drugs to treat mild Alzheimer’s dementia and MCI. But the transition from normal aging to MCI is imprecise, and people with very minimal cognitive impairment get tested, and the meaning of the test results is often misunderstood.

Although the new tau-protein blood test was accurate 90 percent of the time, its accuracy fell in patients in early disease stages. Amyloid and tau can build up in the brain decades before cognition declines, and some people die before dementia develops.

Soon after our PET scan discoveries, I saw a 68-year-old patient, an author and television host, who sought a second opinion about his memory symptoms. He had been misplacing his keys and forgetting names but joked about his senior moments like most of his peers until he volunteered to get an amyloid PET scan—the results terrified him. The neurologist informed him that his brain was riddled with Alzheimer’s disease. My patient was convinced that he was going to lose his mental abilities rapidly, and his heightened anxiety about the future distracted him and made him even more forgetful.

As a practicing geriatric psychiatrist, too often, I observe this gradually progressive disease and the dread it causes my patients and their families. However, when my own mother and mother-in-law—both bright and talented professionals—gradually lost their mental abilities from their disease, I was able to truly understand the suffering these families experience.

The brain abnormalities that these PET scans and blood tests show develop gradually over decades. Unfortunately, doctors, patients, and family members often interpret the test results as positive or negative: Either you have the disease or you don’t. The cognitive impairment from Alzheimer’s, however, doesn’t develop suddenly as it would if someone suffered a massive stroke. The neurodegenerative decline of Alzheimer’s disease is insidious—it progresses like a rheostat rather than an on-off switch.

Some patients with MCI who remain stable or even improve may suffer from medication side effects, untreated physical illnesses, depression, or other conditions, and the treatment of those problems can remediate the cognitive difficulties.

Retired journalist Stephen Gettinger’s essay (The New York Times, June 8, 2024) about his diagnosis of Alzheimer’s disease highlights this issue. At age 74, his gradually progressive forgetfulness and family history of Alzheimer’s disease led him to seek an evaluation. Following an amyloid PET scan and a cognitive pencil-and-paper test, he was informed of his early stage of Alzheimer’s. Mr. Gettinger was shaken by this disclosure, but his mood and cognitive symptoms perked up after a medication adjustment, new eyeglasses, and the removal of hardened earwax, which improved his vision, hearing, and cognitive abilities. In the meantime, his doctors have ordered more tests to clarify his diagnosis.

Brain amyloid deposits alone are not enough to confirm that the disease is progressing quickly, even in the presence of mild memory complaints and minor errors on a written test. The brain accumulation of both amyloid and the other abnormal protein, tau, makes progression more likely. In a study of cognitively unimpaired older adults, 0.5 percent of those negative for both amyloid and tau developed dementia after three years compared with 1.0 percent of those who were amyloid-positive and tau-negative and up to 20 percent for those amyloid-positive with extensive tau deposition. These findings are not surprising since tau accumulation is more closely linked to disease decline than amyloid.

Proponents of amyloid disclosure base their position on a person’s right to know and to engage in early future decision-making. For people with MCI or dementia, it can lead to changes in clinical management, but a clear explanation of the subtleties and predictive value of the information is essential. A negative amyloid PET scan or tau blood test can bring relief and perspective on the forgetfulness of normal aging, but a third of people informed of an elevated amyloid PET report greater awareness of and worry about their memory issues.

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For my 68-year-old patient who felt stigmatized by his diagnosis, I explained the nuances of his test result, which gave him a more realistic expectation of his prognosis and relieved his anxiety. Over the next two decades of his life, he never did develop dementia.



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