The impact of co-occurring pathologies on clinical disease progression may depend on severity of Alzheimer disease neuropathology (ADNP), according to a recent study. Researchers estimated rates of clinical progression and tested whether associations between clinical progression and Alzheimer's disease neuropathology (ADNP) were modified by co-occurring Lewy body disease (LBD) or vascular brain injury (VBI). They used linear mixed effects models to evaluate longitudinal trends in the Clinical Dementia Rating Sum of Boxes on 2,046 autopsied subjects seen at a US Alzheimer's Disease Center, and found:

• Annual clinical progression was slightly faster for ADNP + LBD compared with ADNP only and slightly slower for ADNP + VBI.
• Differences in progression were less than expected if each neuropathology independently contributed to progression; ADNP interacted with LBD and VBI.
• In secondary models, the effect of additional pathologies on clinical progression was greater in those with intermediate compared with high levels of ADNP.