Clinical Manifestations

Area of Science:

• Gerontology
• Genetics
• Neuroscience

Background:

• Mild Cognitive Impairment (MCI) is a precursor to Alzheimer's disease (AD), with varying heritability estimates.
• Heritability for MCI may increase with longer follow-up and consideration of diagnostic stability over time.
• Investigating genetic contributions via polygenic scores (PGS) for AD and education is crucial.

Purpose of the Study:

• To determine the heritability of MCI in later life within a longitudinal twin cohort.
• To assess the influence of AD and educational attainment polygenic scores on MCI risk.
• To examine diagnostic stability's impact on MCI heritability estimates.

Main Methods:

• Longitudinal analysis of 1593 male twins (Vietnam Era Twin Study of Aging) from ages 52.1 to 78.5.
• MCI diagnosis based on Jak/Bondi criteria, adjusting for early cognitive ability; unstable diagnoses were excluded.
• Biometrical analyses modeled heritability, controlling for age; PGS for AD and education were incorporated.

Main Results:

• Heritability for amnestic MCI (aMCI) was estimated at 57.9% (increasing to 61.1% when excluding unstable diagnoses).
• General MCI heritability was 42.1% (increasing to 46.9%), while non-amnestic MCI heritability was not estimable.
• Polygenic scores for AD and education showed minimal association (<1%) with general or aMCI risk.

Conclusions:

• Heritability for amnestic MCI in later life is comparable to AD estimates, highlighting significant genetic influence.
• Current polygenic scores for AD and education do not adequately capture genetic risks for MCI.
• Further research is needed to identify specific genetic factors contributing to MCI development.