Researchers in the Netherlands built a tool that could predict the time to a certain level of cognitive ability decline among people with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They suggest that clinicians could use this tool to explain the expected natural decline of cognitive ability to patients. This could also help clinicians to discuss about approaches that may prevent or delay the decline with their patients.  

Alzheimer’s is a progressive disease that the symptoms get worse over time. After the first symptom occurred, the condition progresses in four stages – mild cognitive impairment, mild, moderate, and severe dementia due to Alzheimer’s. Individuals with mild cognitive impairment show mild changes in their thinking skill and ability to remember things, incuding conversations, recent events, or appointments. While, those symptoms are not significant, people are still able to work, drive, and socialize. The mild dementia stage is where memory and thinking problems become apparent and start affecting the person’s daily activities. People who are at the moderate stage require more help for daily activities and self-care. At the severe stage, individuals lose their ability to have conversations and control their movements. 

It takes many years for the symptoms to progress, which brings large uncertainties for patients and their families. To reduce the uncertainties and help clinicians communicate better about the expected trajectory of the condition, researchers from the Amsterdam University Medical Center developed a prediction tool. With this tool, they aimed to predict the time it takes for individual patient to reach a certain level of cognitive ability decline. 

The team included 310 participants with mild cognitive impairment and 651 with mild dementia from the Amsterdam Dementia Cohort. When the participants just entered the cohort, also called baseline, they all had a positive test result of the amyloid beta protein, a marker for Alzheimer’s. In addition, they had at least two test results of the Mini-Mental State Examination (MMSE), one was at baseline, the rest happened during the follow-up period. The researchers used MMSE score as the main method to evaluate individuals’ cognitive ability, with the score ranging from 0 to 30. Individuals with a score of 25 or higher have normal cognitive ability; the score declines when people have impaired cognitive ability. They also collected participants’ demographic and clinical data, including age, gender, concentrations of protein amyloid beta 1-42 and p-tau in the cerebrospinal fluid, as well as the status of genetic risk factor APOE e4. Based on those data, the team used statistical methods to build a model that could predict the patterns of MMSE change over time.

At baseline, the participants with mild cognitive impairment had an average MMSE score of 26.4, and it was 22.4 among those with mild dementia. Without intervention, all the participants showed noticeable declines in the scores each year. 

For individuals with mild cognitive impairment, the team used the prediction model that included the data of age, gender, levels of protein amyloid beta 1-42 and p-tau. For those with mild dementia, the model included data of age, the level of protein amyloid beta 1-42,  APOE e4 status, and the baseline MMSE score. 

To make personalised predictions of cognitive ability decline with the model, the researchers created a hypothetical patient with mild cognitive impairment or mild dementia. The patient with mild cognitive impairment had a MMSE of 28 and a positive test result of amyloid beta protein at baseline. The average time predicted for this patient to reach MMSE of 20 was six years. For the patient with mild dementia who had a baseline MMSE of 20 and amyloid beta positive, the average time predicted to reach MMSE of 15 was 2.3 years. 

The team also created another hypothetical situation where a patient received a treatment that slowed the decline of cognitive ability by 30%. By using the model, they predicted the time for the patient with mild cognitive impairment to reach a MMSE of 20 was 8.6 years. That was 3.3 years for the patient with mild dementia to reach a MMSE of 15. 

Together with the model, the researchers also included visual function in a calculator to create a prototype tool. With this, they can discuss with patients about information such as the possible outcomes of the disease progression, and the impact of intervention approaches. 

“In the communication of prognostic information to patients, a link needs to be made between the answers models can provide and the questions patients and their care partners have such as how long can I still drive a car or how long can I in my hobby. However, no currently available cognitive test addresses all the questions patients have,” the researchers wrote. 

“In the future, we hope prediction models will become available directly predicting patient-reported outcomes such as quality of life and daily functioning. Until then, there is an important role for clinicians in translating the observed and predicted cognitive function scores into answers to patients’ questions.”

“We attempted to aid clinicians by translating the rate of decline into a clinically meaningful outcome by providing estimations of time to a certain MMSE level.” 

This study was published in Neurology. Image credit: Canva

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