Predicting the rate of cognitive decline in Alzheimer’s patients

A recent study has explored predicting cognitive decline rates in individuals with early Alzheimer’s disease and assessed the impact of newly approved drugs on this decline. 

Focus of the study

“Alzheimer disease (AD) is a progressive neurodegenerative disease with considerable variability in the rate of cognitive decline,” wrote the researchers.

“The disease is highly prevalent, with roughly 100 million people estimated to be in the mild cognitive impairment (MCI) and dementia stages of the disease.” 

“From the MCI stage, it is estimated to take 4 years on average before people have progressed to dementia. New disease-modifying treatments targeting amyloid plaques slow disease progression in the MCI and mild dementia stages of AD. However, the clinical meaningfulness of these medications is debated.”

Variable rate of cognitive decline

Published in the July 10, 2024, online issue of Neurology®, the research aimed to address the variability in cognitive decline, which is a pressing concern for patients and caregivers.

“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 Dr. Pieter J. van der Veere of Amsterdam University Medical Center, Netherlands.

Models to predict cognitive decline 

The researchers developed predictive models to estimate how quickly individuals’ scores on cognitive tests would decline. 

The team validated these models with data from 961 participants, averaging 65 years old – 310 with mild cognitive impairment and 651 with mild dementia. All subjects had amyloid-beta plaques, an early marker of Alzheimer’s, targeted by the new drugs.

Cognitive test scores range from 0 to 30. Participants with mild cognitive impairment had scores drop from 26.4 to 21.0 over five years, while those with mild dementia saw scores fall from 22.4 to 7.8 in the same period. 

Accurate prediction rates

The models accurately predicted the rate of cognitive decline, although with some degree of uncertainty. For half of those with mild cognitive impairment, actual scores differed by less than two points from predictions, and for mild dementia, by less than three points.

A hypothetical case showed that a person with mild cognitive impairment and a baseline score of 28 would reach moderate dementia (score of 20) in six years. 

However, with a drug reducing decline by 30%, this stage would be delayed to 8.6 years. For mild dementia with a baseline score of 21, reaching a score of 15 would take 2.3 years, or 3.3 years with the same treatment.

“Patients with AD and their care partners want to know their future cognitive functioning. Our prediction models can be used to inform patients about their cognitive decline, but our results also indicate that providing a precise prognosis is challenging,” wrote the researchers.

“Thus clinicians need to talk about the inherent uncertainty surrounding the predictions with their patients.^”

The experts noted that visualizations of the uncertainty can form the basis for meaningful doctor-patient conversations about the predicted cognitive decline.

Quality of life and daily functioning 

“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?’” said Dr. Van der Veere. 

“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.” 

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