Increased regional white matter hyperintensity volume in objectively-defined subtle cognitive decline and mild cognitive impairment

White matter hyperintensities (WMH), a marker of small vessel cerebrovascular disease, increase risk of developing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Less is known about the extent and pattern of WMH in pre-MCI stages, such as among those with objectively-defined subtle cognitive decline (Obj-SCD). Five hundred and fifty-nine Alzheimer's Disease Neuroimaging Initiative participants (170 cognitively unimpaired [CU]; 83 Obj-SCD; 306 MCI) free of clinical dementia or stroke completed neuropsychological testing and MRI exams. ANCOVA models compared cognitive groups on regional WMH adjusting for age, sex, and apolipoprotein E (APOE) e 4 frequency. Compared with the CU group, those with Obj-SCD had greater temporal, occipital, and frontal WMH whereas those with MCI had higher WMH volume across all regions ( p 's < 0.01). No differences in WMH volume were observed between the Obj-SCD and MCI groups ( p 's > 0.05). Findings add to growing evidence of associations between Obj-SCD and imaging biomarkers, providing support for utility of these criteria to capture subtle cognitive changes that are biologically based.

Automated summary

White matter hyperintensities (WMH), a marker of small vessel cerebrovascular disease, increase the risk of developing mild cognitive impairment (MCI) and Alzheimer's disease (AD). This study found that individuals with objectively-defined subtle cognitive decline (Obj-SCD) had greater WMH in the temporal, occipital, and frontal regions compared to cognitively unimpaired individuals (CU). Those with MCI had higher WMH volume across all regions. The findings support the use of Obj-SCD criteria to capture biologically-based cognitive changes.