Differences in Alzheimer’s disease and cerebrovascular disease neuropathology between latent class groups of cardiovascular risk factors

Background Individual cardiovascular risk factors (CVRFs) have been associated with neurodegeneration. However, CVRFs are often comorbid with one another, and little is known regarding how groups of co‐occurring CVRFs are associated with Alzheimer’s disease (AD)‐ and cerebrovascular disease (CVD)‐related neuropathologies. We identify distinct groups of CVRFs in cognitively normal (CN) individuals with post‐mortem data. Method Individuals from the National Alzheimer’s Coordinating Center dataset who were CN one year prior to death were analyzed. To identify CVRF classes, a latent class analysis (LCA) was conducted with seven CVRFs (hypertension, hypercholesterolemia, heart condition, stroke, and smoking history, diabetes, and obesity). Differences in the presence of 1) mixed AD neuropathology (ADNP) and CVD neuropathology (CVNP), and 2) CVNP only, were compared between CVRF groups. Age, sex, years of education, Mini‐Mental State Examination (MMSE) score, and presence of APOE E4 allele were included as covariates. The presence of pure ADNP was not investigated as this was only present in two individuals. Result This study included 415 CN individuals (age of death: 86.2+/‐9.6, MMSE: 28.3+/‐1.8, education: 15.8+/‐2.8 years, male = 53%, APOE E4 allele: 21%). The LCA identified three groups of CVRFs (Figure 1). One group had low probabilities of CVRFs (N = 89). The second group had higher probabilities of hypertension and hypercholesterolemia (N = 255) (vascular‐dominant group). The third group had higher probabilities of hypertension, hypercholesterolemia, smoking history, diabetes, and obesity (vascular‐metabolic group) (N = 71). The vascular‐dominant group had significantly more individuals with mixed ADNP/CVNP than the vascular‐metabolic group (24% vs. 9%, p = .014). However, the vascular‐metabolic group had significantly more individuals with CVNP only compared to the vascular‐dominant group (61% vs. 37%, p = .002). Conclusion These findings suggest that those in the vascular‐dominant group have an increased odds of having mixed ADNP/CVNP, while those in the vascular‐metabolic group have an increased odds of having increased CVNP only. Future studies targeting ADNP/CVNP in the vascular‐dominant group, and CVNP in the vascular‐metabolic group should be investigated to determine their modifying effects on cognitive‐related outcomes.