A Multimodal Approach to Stratification of Patients with Dementia: Selection of Mixed Dementia Patients Prior to Autopsy

Abstract

Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) are major causes of dementia, and when combined lead to accelerated cognitive loss. We hypothesized that biomarkers of neurodegeneration and neuroinflammation could be used to stratify patients into diagnostic groups. Diagnosis of AD can be made biologically with detection of amyloid and tau proteins in the cerebrospinal fluid (CSF) and vascular disease can be identified with diffusion tensor imaging (DTI). We recruited patients with cognitive complaints and made an initial clinical diagnosis. After one year of follow-up we made a biological diagnosis based on the use of biomarkers obtained from DTI, CSF AD, and inflammatory proteins, and neuropsychological testing. Patients with AD had primarily findings of neurodegeneration (CSF showing increased tau and reduced amyloid), while patients with neuroinflammation had abnormal DTI mean diffusion (MD) in the white matter. Using the biological biomarkers resulted in many of the clinically diagnosed AD patients moving into mixed dementia (MX). Biomarkers of inflammation tended to be higher in the MX than in either the AD or VCID, suggesting dual pathology leads to increased inflammation, which could explain accelerated cognitive decline in that group.

Keywords

• vascular cognitive impairment
• Alzheimer’s disease
• mixed dementia
• biomarkers
• cerebrospinal fluid
• diffusion tensor imaging
• neurodegeneration
• neuroinflammation