Association of vascular and degenerative brain pathologies and past medical history from the National Alzheimer’s Coordinating Center Database

Abstract

The relationship between past medical histories (PMH) and dementia-related neuropathologies is not well understood. Using the National Alzheimer's Coordinating Center (NACC) database, we explored the relationship between patient-reported PMH and various vascular and degenerative neuropathologies. We examined the following PMH: transient ischemic attack (TIA), stroke, traumatic brain injury, seizures, hypertension, cardiovascular events, hypercholesterolemia, B12 deficiency, diabetes mellitus, and thyroid disease. We dichotomized the following neuropathologies: atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy (CAA), Alzheimer disease neuropathology (ADNP), Lewy bodies (LB), hippocampal sclerosis, frontotemporal lobar degeneration (FTLD), and TAR DNA-binding protein-43 (TDP-43). Separate logistic regression models assessed the relationship between the outcome of individual neuropathologies and all PMHs. Additional logistic regressions were stratified by sex to further examine these associations. Hypertension history was associated with an increased likelihood of atherosclerosis (OR = 1.7) and arteriolosclerosis (OR = 1.3), but decreased odds of ADNP (OR = 0.81), CAA (OR = 0.79), and LB (OR = 0.78). History of TIA was associated with an increased likelihood of atherosclerosis (OR = 1.3) and arteriolosclerosis (OR = 1.4) and lower odds of ADNP (OR = 0.72). Seizure history was associated with an increased likelihood of ADNP (OR = 1.9) and lower odds of FTLD (OR = 0.49). Hypertension history was associated with a greater likelihood of vascular pathologies yet a lower likelihood of ADNP and other neurodegenerative pathologies.

Disentangling and quantifying the relative cognitive impact of concurrent mixed neurodegenerative pathologies

“…Data for this study were downloaded with permission from the NACC (sourced from 37 ADRC collection centers located across the United States), which is a widely utilized cohort with available neuropathologic and neurocognitive data [ 7 – 9 , 13 , 23 – 28 , 30 , 39 , 54 , 67 , 71 , 72 , 79 – 81 , 91 , 93 , 95 ], established with funding from the National Institute on Aging (U01 AG016976) ( https://naccdata.org/ ). We utilized standardized Uniform Data Set (UDS), version 3 variable definitions ( https://naccdata.org/data-collection/forms-documentation/uds-3 ), Neuropathology (NP) Data Set, version 11 variable definitions ( https://naccdata.org/data-collection/forms-documentation/np-11 ), and Genetic Data Set (Gen) variable definitions ( https://files.alz.washington.edu/documentation/rdd-genetic-data.pdf ) from NACC, as previously described [ 4 , 5 , 93 ].…”