Do age and episodic memory task performance differentially relate to tract-specific white matter microstructure? Cross-sectional and longitudinal analyses in a healthy adult sample.

Both delayed free recall and white matter microstructure decreased significantly with age in cross-sectional analyses.

• Cross-sectional sample included n=301 cognitively normal adults with a mean age of 52.4 years and an age range of 19-85.
• Age-related declines were observed across WMM measures in tracts associated with episodic memory: the fornix, superior longitudinal fasciculus, uncinate fasciculus, and cingulum bundle.
• Delayed free recall performance declined significantly with advancing age across the adult lifespan.

When modeled together, age predicted delayed free recall, whereas WMM was associated with delayed recall performance only in the fornix above and beyond variance explained by age.

• Cross-sectional analyses modeled age and WMM together to predict delayed free recall performance.
• Of all tracts examined (fornix, superior longitudinal fasciculus, uncinate fasciculus, cingulum bundle), only fornix WMM uniquely predicted delayed free recall beyond age.
• Age remained a significant predictor of delayed free recall even after WMM was included in the model.

Longitudinal changes in white matter microstructure did not significantly predict changes in delayed free recall performance over time.

• The longitudinal sample included n=147 cognitively normal adults with a baseline mean age of 56.36 years and a range of 38-71.
• Changes in WMM across tracts were not significantly associated with changes in delayed free recall performance longitudinally.
• Advancing age was also not a strong predictor of changes in WMM over the longitudinal follow-up period.

Advancing age was not a strong predictor of changes in white matter microstructure over time in the longitudinal sample.

• The longitudinal sample had a baseline age range of 38-71 years.
• Despite cross-sectional evidence of age-related WMM decline, longitudinal analyses did not confirm age as a strong driver of WMM change over the observed follow-up period.
• This discrepancy between cross-sectional and longitudinal findings suggests cohort or survivor effects may influence cross-sectional age-WMM associations.

The study focused on episodic memory-associated tracts including the fornix, superior longitudinal fasciculus, uncinate fasciculus, and cingulum bundle in cognitively normal adults.

• Participants were drawn from the Nathan Kline Institute Rockland Sample.
• Cognitive normality was a criterion for inclusion in both cross-sectional (n=301) and longitudinal (n=147) samples.
• White matter microstructure (WMM) was examined in tracts specifically associated with episodic memory function.
• Episodic memory was indexed by delayed free recall performance.