New Algorithms Forecast How Fast Alzheimer’s Progresses

Alzheimer's Disease Acceleration Art Concept

A study investigated predictive models for cognitive decline in early Alzheimer’s patients, examining the impact of new drugs that target amyloid-beta plaques. Researchers developed models comparing predicted declines in cognitive test scores with actual outcomes, observing both the accuracy of these predictions and the potential delay in decline due to drug treatments. Credit:

A 2024 study assesses predictive models for Alzheimer’s-related cognitive decline and evaluates new drugs’ effectiveness in slowing this decline.

A new study looks at predicting how quickly people with early Alzheimer’s disease will experience cognitive decline. The study is published in the July 10, 2024, online issue of Neurology, the medical journal of the American Academy of Neurology. It also looked at how the new drugs recently approved for the disease may reduce decline.

“The rate of cognitive decline varies greatly from person to person, and people are very interested in what to expect from the disease in themselves or their loved ones, so better prediction models are urgently needed,” said study author Pieter J. van der Veere, M.D., of Amsterdam University Medical Center, Netherlands.

Study Details and Cognitive Assessment

The researchers developed models to predict how quickly people’s scores would decline on a test of thinking and memory skills. Then they compared the models to actual results from people over time. They studied 961 people with an average age of 65—310 had mild cognitive impairment and 651 had mild dementia. All had the amyloid-beta plaques in their brains that are an early sign of Alzheimer’s disease and are targeted by the new drugs.

For the cognitive test, scores range from zero to 30, with scores of 25 and higher indicating no dementia, scores of 21 to 24 indicating mild dementia, scores of 10 to 20 indicating moderate dementia and scores lower than 10 indicating severe dementia. The test scores of the people with mild cognitive impairment declined from 26.4 at the beginning of the study to 21.0 five years later. The scores of people with mild dementia declined from 22.4 to 7.8 five years later.

Insights From Cognitive Decline Models

The models were helpful in predicting the rate of cognitive decline, but also show the uncertainty of these predictions, van der Veere noted. For half of the people with mild cognitive impairment, the actual test score differed by less than two points from the predicted score. For the people with mild dementia, the scores differed by less than three points for half of the people.

Predictive Outcomes and Drug Impact

The researchers determined that a hypothetical person with mild cognitive impairment, a baseline test score of 28 and a certain level of amyloid plaques would be predicted to reach the stage of moderate dementia (test score of 20 points) after six years. When a treatment with drugs would reduce the rate of decline by 30%, this person would not reach the stage of moderate dementia until after 8.6 years. For a hypothetical person with mild dementia, a baseline score of 21 and a certain level of amyloid, the predicted time to reach a score of 15 points was 2.3 years, or 3.3 years when decline would be reduced by 30%.

Future Applications and Study Limitations

Van der Veere said, “We understand that people with cognitive problems and their care partners are most interested in answers to questions like ‘How long can I drive a car?’ or ‘How long can I keep doing my hobby?’ In the future, we hope that models will help make predictions about these questions about quality of life and daily functioning. But until then, we hope these models will help physicians translate these predicted scores into answers for people’s questions.”

A limitation of the study was that the cognitive tests were not always given at the same time of day and people with cognitive decline may score lower later in the day when they are more tired.

Reference: “Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia” by Pieter J. van der Veere, Jeroen Hoogland, Leonie N.C. Visser, Argonde C. Van Harten, Hanneke F. Rhodius-Meester, Sietske A.M. Sikkes, Vikram Venkatraghavan, Frederik Barkhof, Charlotte E. Teunissen, Elsmarieke van de Giessen, Johannes Berkhof and Wiesje M. Van Der Flier, 10 July 2024, Neurology.
DOI: 10.1212/WNL.0000000000209605

The study was supported by Eisai, ZonMW and Health~Holland, Top Sector Life Sciences & Health.

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