Resistance and resilience to Alzheimer’s disease pathology associated with lower severity of other neuropathologic diseases

Abstract

AbstractBackgroundOlder adults with multiple types of neuropathologic disease may be at higher risk for cognitive impairment, but the impact of specific combinations of disease on cognition is unclear. Alzheimer’s disease neuropathologic change (ADNC) is the most common neuropathologic disease found in dementia cases. Cognitively normal participants without ADNC are “resistant”; those with ADNC are “resilient.” To determine if resistant and resilient participants have lower levels of non‐AD neuropathologic diseases, we compared neuropathologic features against participants with clinical Alzheimer’s dementia.MethodWe included autopsied participants from the National Alzheimer’s Coordinating Center Uniform Data Set whose last visit was within two years of death. Participants were excluded if they had rare neuropathologic diseases or were not evaluated for each neuropathologic feature. For both resilient (normal cognition, moderate or high NIA‐AA ADNC score) and resistant (85+ years old, normal cognition, no or low NIA‐AA ADNC score) individuals, we calculated the odds of having non‐AD pathologic features against a control group (moderate or high NIA‐AA ADNC score, clinical dementia), adjusting for age at death, sex, education, and presence of APOE e4 allele(s). Features included vascular pathology (number of infarcts and microinfarcts; severity of arteriosclerosis, atherosclerosis, and cerebral amyloid angiopathy), Lewy body disease (LBD) staging, and limbic‐predominant age‐related transactive response DNA‐binding protein 43 encephalopathy (LATE‐NC) staging.ResultOf 1,190 participants who met inclusion criteria, 59 were resistant, 41 were resilient, and 1,090 were controls. Both resistant and resilient participants had lower severity of LATE‐NC (resistant aOR: 0.23, 95% CI: 0.19‐0.27; resilient aOR: 0.49, 95% CI: 0.42‐0.56) and LBD (resistant aOR: 0.71, 95% CI: 0.63‐0.80; resilient aOR 0.52, 95% CI 0.44‐0.60). Resistant individuals also had lower odds of CAA, and resilient individuals had lower odds of arteriosclerosis.ConclusionResistance and resilience to ADNC is associated with lower odds of other neuropathologic disease, including Lewy bodies and LATE‐NC. This supports prior research indicating an interactive effect of multiple neuropathologic diseases on risk of dementia, and specifically that having LBD or LATE‐NC contributes to the risk of developing Alzheimer’s dementia. Understanding how to prevent LBD and LATE‐NC could lead to higher resistance and resilience to Alzheimer’s dementia.