Affect of APOE on information processing speed in non-demented elderly population: a preliminary structural MRI study

APOE is one of the strongest genetic factors associated with information processing speed (IPS). Herein, we explored the neural substrates underlying APOE-related IPS alteration by measuring lobar distribution of white matter hyperintensities (WMH), cortical grey matter volume (GMV) and thickness. Using the ADNI database, we evaluated 178 cognitively normal elderly individuals including 34 APOE epsilon 2 carriers, 54 APOE epsilon 4 carriers and 90 epsilon 3 homozygotes. IPS was determined using Trail Making Tests (TMT). We quantified lobar distribution of WMH, cortical GM lobar volume, cortical thickness among three groups. Finally, we used Pearson's correlation and general linear models to examine structural MRI markers in relation to IPS. There were significant differences of IPS among groups, with epsilon 4 carriers displaying the worst performance. Across groups, significant differences in frontal and parietal WMH load were observed (the highest in epsilon 4 carriers); however, no significant differences in cortical GMV and thickness were found. Pearson's correlation analysis showed parietal WMH volume was significantly related with IPS, especially in epsilon 4 carriers. Subsequently a general linear model demonstrated that parietal WMH volume, age and the interaction between parietal WMH volume and age, was significantly associated with IPS, even after adjusting total intracranial volume (TIV), gender and vascular risk factors. Disruption of WM structure, rather than atrophy of GM, plays a more critical role in APOE epsilon 4 allele-specific IPS. Moreover, specific WMH loci are closely associated with IPS; increased parietal WMH volume, especially in epsilon 4 carriers, was independently contributed to slower IPS.