Objective:

To investigate the moderating role of cognitive reserve (CR) on the relationship between white matter hyperintensity (WMH) and cognitive performance in individuals on the Alzheimer's disease (AD) spectrum using specific cognitive tests.

Background:

WMH is known to contribute to cognitive decline in AD, regardless of AD-related pathology. CR has been proposed to buffer cognitive performance against brain pathology, but its role in moderating the effects of WMH within the context of AD remains uncertain.

Design/Methods:

A total of 88 participants with cognitive impairment (mild cognitive impairment and AD) and 68 cognitively healthy individuals were enrolled. Cognitive tests, including the Montreal Cognitive Assessment (MoCA), the Digit Span subtest of WAIS-IV, the Benson Figure test, the Boston Naming Test, and a 12-item memory test, were administered. MRI scans (cortical thickness, hippocampal volume, and WMH) and the Cognitive Reserve Index questionnaire were also conducted.

Results:

In the cognitively impaired group, multiple regression analysis indicated that CR positively predicted MoCA scores (β= .27, p= .035). Additionally, CR*WMH interaction was significant with the Digit Span backward subtest (β= .46, p= .012), the Benson Figure test-copy (β= .70, p < .001), and the Boston Naming test (β= .56, p < .001) scores as dependent variables. Simple slope tests revealed higher CR was associated with gentler slopes than lower CR for backward Digit Span (b= -0.63, p <. 001 for high; b= -1.59, p= .002 for low), copy (b= -0.60, p= 006 for high; b = -1.85, p < .001 for low), and naming (b= -0.36, p= .018 for high; b= -1.23, p < .001 for low) scores. No significant CR*AD signature or CR*hippocampus interactions were detected. No any significant interactions were observed in the cognitively healthy group.

Conclusions:

CR mitigates the negative impact of white matter lesions on non-memory cognitive functions, independent of AD-related pathology.