The impact of arteriolosclerosis on cognitive impairment in decedents without severe dementia from the National Alzheimer's Coordinating Center

Abstract

INTRODUCTION: Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular neuropathologies occur together. Previous studies have been limited by a large majority of participants with severe dementia or advanced stages of pathologies, which limits the detectability of cognitive effects from vascular neuropathologies. METHODS: Using neuropathology data from the National Alzheimer's Coordinating Center, we examined the association of vascular neuropathologies with cognitive scores in participants without severe dementia (N = 1526) using multivariable linear regression. RESULTS: Controlling for age, sex, education, LBD, and ADNC, arteriolosclerosis was associated with lower memory (β = −0.16 ± 0.06, p < 0.001), executive function (β = −0.25 ± 0.05, p < 0.001), and language scores (β = −0.20 ± 0.05, p < 0.001). The effects of arteriolosclerosis remained when controlling for vascular risk factors. DISCUSSION: Vascular neuropathologies exhibit distinct relationships with cognition. Arteriolosclerosis is an independent contributor to cognition. Further research should be conducted on whether arteriolosclerosis can serve as a surrogate marker for cognitive decline in early disease stages. Highlights: In individuals who do not have severe dementia, vascular neuropathologies are common, and the combination of pathologies is heterogeneous in a convenience sample from the Alzheimer's Disease Research Center that reported all the neuropathology data elements for this investigation. Arteriolosclerosis is associated with several cognitive domain scores, including memory, executive function, and language when controlling for the effects of Alzheimer's disease neuropathologic change and Lewy body disease. These results reinforce the importance of vascular pathology for cognition among people along the Alzheimer's disease spectrum.