In this study, we leveraged the large-scale National Alzheimer’s Coordinating Center (NACC) database to study the associations between past medical histories (PMH) and common neuropathologies.

The relationship between PMH and common dementia-related degenerative and vascular pathologies is less well understood.

5357 NACC participants had both neuropathological and PMH data available. PMH variables of interest included hypertension, transient ischemic attack (TIA), seizures, traumatic brain injury (TBI), hypercholesterolemia, diabetes, thyroid disease, and B12 deficiency. We considered the following neuropathologies dichotomized as present/absent: atherosclerosis, arteriolosclerosis, Alzheimer’s disease neuropathology (ADNP), cerebral amyloid angiopathy (CAA), frontotemporal lobar degeneration (FTLD), hippocampal sclerosis (HS), and Lewy bodies. Linear regressions adjusted for age at death, sex, and education determined the association between PMH and neuropathologies.

Hypertension history had contrasting associations with vascular vs. degenerative pathologies; it was associated with increased likelihood of atherosclerosis (B= 0.117, t= 7.189, p< 0.001) and arteriolosclerosis (B= 0.050, t= 2.756, p= 0.006) but decreased likelihood of ADNP (B= -0.052, t=-3.006, p=0.003), CAA (B=-0.056, t=-3.229, p=0.001), and Lewy bodies (B=-0.055, t=-3.189, p=0.001). Also, while history of TIA was associated with increased likelihood of atherosclerosis (B=0.050, t=3.259, p=0.001) and arteriolosclerosis (B= 0.070, t= 4.073, p= < 0.001), it was associated with decreased likelihood of ADNP (B= -0.050, t= -3.076, p= 0.002). Additionally, diabetes was associated with reduced likelihood of Lewy bodies (B=-0.034, t=-2.090, p=0.037), hypercholesterolemia was associated with reduced likelihood of CAA (B=0.037, t=2.174, p=0.030), and seizures were associated with increased likelihood of ADNP (B=0.079, t=4.906, p< 0.001) and CAA (B=0.042, t=2.605, p=0.009) and reduced likelihood of FTLD (B=-0.064, t=-4.094, p< 0.001).

Our results suggest that while a history of hypertension is detrimental to the brain vasculature leading to increased likelihood of vascular pathologies, it may reduce the likelihood of neurodegeneration via preservation of brain perfusion.