Alzheimer Dementia: In the early stage of dementia, multiple markers can be combined to predict the progression of dementia

The individual prognosis of patients with Alzheimer's disease (AD) or the ability to detect therapeutic effects in interventional clinical trials for neurodegenerative diseases are often hindered by huge differences in disease progression at the patient level
.

In the AD dementia stage, as the speed of cognitive and functional deterioration continues to increase during the course of the disease, baseline cognitive ability is the main predictor of future decline speed, which has been confirmed

In the pre-dementia stage, there are usually few or no measurable cognitive deficits, and changes in cognitive scores are more related to non-disease-specific differences than disease pathological burdens

The dramatic changes in the trajectory of the disease between individuals obscure the signal of treatment effectiveness, forcing AD trials to be conducted extensively and at high cost
.

Each experimental group requires a sample size of up to 2000 patients and follow-up within 4 years to make the moderately effective drugs for preclinical AD reach 80% power

Traditionally, the prognosis of an individual’s future cognitive progress is based on cognitive standards
.

However, because more attention is focused on selecting patients in the early stages of dementia, cognitive standards are of limited value for recruiting homogenized patient groups because of the future cognitive progress of two patients with similar cognitive levels There may be a big difference

Using such methods, it has previously been demonstrated that the progression of individual patients along the disease continuum can be predicted by a combination of biomarkers
.

However, this prediction model needs to collect CSF, magnetic resonance imaging (MRI) and two positron emission tomography (PET) at the same time, which makes its implementation in clinical practice very impractical
.

In addition, these forecast results have not been externally verified

In this way, Line Kühnel1 of the University of Copenhagen and others have developed and verified a continuous prediction model based on biomarkers, which allows to reduce the test sample size while defining the personal cognitive prognosis at any time in the future
.

The model was developed using data from the MEMENTO study and externally verified using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study

They modeled the disease progression of the longitudinal cognitive scores of pre-dementia patients (baseline clinical dementia score ≤0.

5) to derive biomarker characteristics that predict patients' cognitive progression during the continuous course of dementia

Among the 9 candidate biomarkers developed and analyzed, 3 cerebrospinal fluid and 2 magnetic resonance imaging measures were selected to form the final biomarker archive
.

When biomarker information is added on the basis of cognitive and demographic data, the model-based prognosis of individuals with cognitive deficits in the future has been shown to be significantly improved

In the calculation of test power, the main analysis is adjusted for the baseline biomarker data, and the sample size requirement can be reduced by ≈10%
.

In the calculation of test power, the main analysis is adjusted for the baseline biomarker data, and the sample size requirement can be reduced by ≈10%
.

Compared with traditional cognitive cut-off points, the inclusion criteria based on biomarker feature cut-off points have reduced the sample size requirement by 28% due to the increased homogeneity of the progress pattern
.

The biomarker profile can predict the personalized trajectory of future cognitive progress
.
This enables accurate and personalized prognosis in clinical care and better selection of patient populations for clinical trials
.

This enables accurate and personalized prognosis in clinical care and better selection of patient populations for clinical trials
.

Original source:
Kühnel L, Bouteloup V, Lespinasse J, et al.
Personalized prediction of progression in pre-dementia patients based on individual biomarker profile: A development and validation study.
Alzheimer's & Dementia .
Published online September 28, 2021:alz.
12363 .
doi:10.
1002/alz.
12363

Personalized prediction of progression in pre‐dementia patients based on individual biomarker profile: A development and validation study.
Alzheimer's & Dementia

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