Medial Temporal Atrophy in Amyloid-Negative Amnestic Type Dementia Is Associated with High Cerebral White Matter Hyperintensity

Abstract

Background:

Non-amyloid mechanisms behind neurodegeneration and cognition impairment are unclear. Cerebrovascular disease (CVD) may play an important role in suspected non-Alzheimer’s pathophysiology (SNAP), especially in Asia.

Objective:

To examine the association between CVD and medial temporal lobe atrophy (MTA) in amyloid-β negative patients with mild amnestic type dementia.

Methods:

Thirty-six mild dementia patients with complete neuropsychological, cerebrospinal fluid (CSF) biomarker, and neuroimaging information were included. Only patients with clinically significant MTA were recruited. Patients were categorized based on their CSF Aβ levels. Neuroimaging and neuropsychological variables were analyzed.

Results:

Despite comparable MTA between Aβ positive and negative patients, Aβ-negative patients had significantly greater white matter hyperintensities (WMH; Total Fazekas Rating) than their Aβ-positive counterparts (6.42 versus 4.19, p = 0.03). A larger proportion of Aβ-negative patients also had severe and confluent WMH. Regression analyses controlling for baseline characteristics yielded consistent results.

Conclusion:

Our findings demonstrate that MTA is associated with greater CVD burden among Aβ-negative patients with amnestic type dementia. CVD may be an important mechanism behind hippocampal atrophy. This has implications on clinical management strategies, where measures to reduce CVD may slow neurodegeneration and disease progression.