ABSTRACT
BACKGROUND: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes. OBJECTIVE: Investigate the contributions of vascular factors and cancer to dementia and neuropathology. METHODS: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology. RESULTS: Participants (nâ=â161; 83% female; 99% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE É2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; pâ=â0.03), but APOE É4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; pâ=â0.03) associated with 56% lower dementia odds (odds ratio [OR]â=â0.44 [confidence interval (CI)â=â0.19-0.98]; pâ=â0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (ORâ=â8.42 [CIâ=â1.39-163]; pâ=â0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; pâ=â0.05). Cancer associated with 63% lower dementia odds (ORâ=â0.37 [CIâ=â0.17-0.78]; pâ<â0.01) and lower Braak stage (pâ=â0.01). CONCLUSION: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-ß plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.
Subject(s)
Alzheimer Disease , Cerebrovascular Disorders , Coronary Artery Disease , Diabetes Mellitus , Neoplasms , Nervous System Diseases , Female , Humans , Aged, 80 and over , Male , Alzheimer Disease/pathology , Neuropathology , Plaque, Amyloid/pathology , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/pathology , Apolipoproteins E , Diabetes Mellitus/epidemiology , Comorbidity , Neoplasms/epidemiologyABSTRACT
The objective of this study was to determine the differential mapping of plasma biomarkers to postmortem neuropathology measures. We identified 64 participants in a population-based study with antemortem plasma markers (amyloid-ß [Aß] x-42, Aßx-40, neurofilament light [NfL], and total tau [T-tau]) who also had neuropathologic assessments of Alzheimer's and cerebrovascular pathology. We conducted weighted linear-regression models to evaluate relationships between plasma measures and neuropathology. Higher plasma NfL and Aß42/40 ratio were associated with cerebrovascular neuropathologic scales (p < 0.05) but not with Braak stage, neuritic plaque score, or Thal phase. Plasma Aß42/40 and NfL explained up to 18% of the variability in cerebrovascular neuropathologic scales. In participants predominantly with modest levels of Alzheimer's pathologic change, biomarkers of amyloid and neurodegeneration were associated with cerebrovascular neuropathology. NfL is a non-specific marker of brain injury, therefore its association with cerebrovascular neuropathology was expected. The association between elevated Aß42/40 and cerebrovascular disease pathology needs further investigation but could be due to the use of less specific amyloid-ß assays (x-40, x-42).