Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology

Abstract

Introduction: Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood.

Methods: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aβ, as assessed by ¹⁸F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape.

Results: Frontal WMH, occipital WMH, and Aβ were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aβ. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aβ-vulnerable subregions.

Discussion: Hippocampal degeneration is differentially sensitive to SVD and Aβ pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia.

Trial registration: ClinicalTrials.gov NCT02330510.

Keywords: Alzheimer's disease; Medical Imaging Trials Network of Canada C6 Project; amyloid; biomarker; cerebral small vessel disease; hippocampal shape; hippocampal volume; mixed dementia; neurodegeneration; vascular; white matter hyperintensities.