Public Health

Area of Science:

• Neuroscience
• Genetics
• Psychology

Background:

• Alzheimer's disease and related dementias (ADRD) prevention requires understanding preclinical pathology.
• Quantifying lifelong risk accumulation is key to identifying individuals at risk for cognitive decline.
• The Louisville Twin Study (LTS) uniquely combines childhood and midlife data to study cognitive decline factors.

Purpose of the Study:

• To develop and validate a Lifespan Cognitive Health Risk (LCHR) score.
• To identify childhood and midlife risk and protective factors for cognitive decline.
• To leverage a twin study framework for stronger causal inference regarding ADRD risk factors.

Main Methods:

• Analysis of 432 middle-aged twins from the Louisville Twin Study (LTS).
• Utilized childhood and midlife IQ assessments (WISC, WAIS-IV) and comprehensive midlife data.
• Developed LCHR scores using regression-weighted and unit-weighted methods, followed by twin analyses.

Main Results:

• Childhood IQ strongly predicted adult IQ (r=0.79).
• Protective factors included higher childhood socioeconomic status and education; risk factors included childhood trauma, smoking, psychopathology, and reduced physical function.
• Identified polygenic index for cognitive ability and accelerated DNA methylation age as risks. Higher LCHR predicted greater IQ decline within twin pairs.

Conclusions:

• The LCHR is a feasible, inexpensive, multidomain risk index for ADRD and cognitive decline.
• The twin framework enhances causal inference for risk and protective factors.
• This index advances prediction models for cognitive decline by incorporating lifelong risk assessment.