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Staging the cognitive continuum in prodromal Alzheimer's disease with episodic memory
Alexis Moscoso1, Jesús Silva-Rodríguez1, Jose Manuel Aldrey2
1Nuclear Medicine Department and Molecular Imaging Group, University Hospital CHUS-IDIS, Santiago de Compostela, Spain.
Abstract:
It is unclear whether episodic memory is an appropriate descriptor of the cognitive continuum in mild cognitive impairment (MCI). Here, we investigated the ability of episodic memory to track cognitive changes in patients with MCI with biomarker evidence of Alzheimer's disease (AD). We examined 387 MCI amyloid-positive subjects, cognitively staged as "early" or "late" on the basis of episodic memory impairment. Cross-sectional and longitudinal comparisons between these 2 groups were performed for each amyloid, tau, and neurodegeneration (AT(N)) profile. Cross-sectional analyses indicate that "early" MCI represents a transitional phase between normal cognition and "late" MCI in the AD biomarker pathway. After adjusting by confounders and levels of A, T, and (N), "late" MCI progressed significantly faster than "early" MCI only in profiles with both abnormal amyloid and tau markers (A+T+(N)- p < 0.05, A+T+(N)+ p < 0.001). Episodic memory staging is useful for describing symptoms in prodromal AD and complements the AT(N) profiles. Our findings might have implications for the Numeric Clinical staging scheme of the National Institute on Aging and Alzheimer's Association research framework.
Insights
Episodic memory staging effectively tracks cognitive changes in mild cognitive impairment (MCI) patients with Alzheimer's disease (AD) biomarkers. Late MCI progresses faster than early MCI, particularly with abnormal amyloid and tau markers.
Area of Science:
- Neuroscience
- Neurology
- Biomarkers in Disease
Background:
- Mild cognitive impairment (MCI) represents a transitional stage, but its cognitive continuum, especially in relation to Alzheimer's disease (AD) biomarkers, requires clarification.
- Episodic memory impairment is a hallmark of prodromal AD, yet its utility in staging cognitive decline within the MCI spectrum is debated.
Purpose of the Study:
- To investigate the efficacy of episodic memory impairment as a descriptor for tracking cognitive changes in individuals with MCI and biomarker evidence of AD.
- To compare the progression rates of "early" and "late" MCI stages based on episodic memory impairment within different amyloid, tau, and neurodegeneration (AT(N)) biomarker profiles.
Main Methods:
- Cross-sectional and longitudinal analyses were conducted on 387 amyloid-positive MCI subjects, stratified into "early" and "late" stages based on episodic memory performance.
- Comparisons were made across various AT(N) profiles (A, T, N) to assess disease progression in relation to cognitive staging.
Main Results:
- Cross-sectional data suggest "early" MCI serves as a bridge between normal cognition and "late" MCI within the AD biomarker pathway.
- Longitudinal analyses, adjusted for confounders and AT(N) levels, revealed significantly faster progression in "late" MCI compared to "early" MCI, specifically in profiles with both amyloid and tau abnormalities (A+T+(N)- and A+T+(N)+).
Conclusions:
- Episodic memory staging is a valuable tool for characterizing symptoms in prodromal AD and complements existing AT(N) biomarker profiles.
- These findings support the utility of episodic memory in clinical staging of AD and may inform future research frameworks, such as the NIA-AA staging scheme.