A Novel Cognitive Frailty Index for Geriatric Mice

Area of Science:

• Gerontology
• Neuroscience
• Biomedical Research

Background:

• Cognitive decline is a major aging challenge, necessitating better models for Geroscience interventions.
• Aged mice model human cognitive aging, but longitudinal data, especially in mice over 30 months, is limited.
• Physical impairments in aged mice can confound cognitive testing.

Purpose of the Study:

• To conduct a comprehensive longitudinal assessment of cognitive changes in aged mice.
• To introduce and validate a novel metric, the Cognitive Frailty Index (CoFI), for assessing cognitive frailty.
• To differentiate between physical and cognitive frailty and their combined impact on mortality.

Main Methods:

• Longitudinal Barnes Maze testing in a cohort of 424 aged C57BL/6J mice (≥21 months).
• Development of the Cognitive Frailty Index (CoFI) integrating Barnes Maze parameters.
• Establishment of a CoFI cut-off and a physically adjusted CoFI.

Main Results:

• CoFI strongly correlates with age and mortality, distinguishing between long- and short-lived mice.
• A physically adjusted CoFI and a specific cut-off effectively separate cognitive from physical frailty.
• Combining physical and cognitive frailty metrics enhances short-term mortality prediction.

Conclusions:

• CoFI provides a robust measure for assessing age-related cognitive decline and frailty in mice.
• The CoFI methodology is adaptable to other cognitive tests and frailty indices.
• CoFI shows potential for evaluating Geroscience interventions targeting cognitive aging.