Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old

Christian Lachner, Gregory S. Day, Gamze Balci Camsari, Naomi Kouri, Nilüfer Ertekin-Taner, Bradley F. Boeve, Sydney A. Labuzan, John A. Lucas, E. Aubrey Thompson, Habeeba Siddiqui, Julia E. Crook, Janisse N. Cabrera-Rodriguez, Keith A. Josephs, Ronald C. Petersen, Dennis W. Dickson, R. Ross Reichard, Michelle M. Mielke, David S. Knopman, Neill R. Graff-Radford, Melissa E. Murray

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1 Scopus citations

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 (n = 161; 83% female; 99% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19-0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39-163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17-0.78]; p < 0.01) and lower Braak stage (p = 0.01). 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-β 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.

Original languageEnglish (US)
Pages (from-to)405-417
Number of pages13
JournalJournal of Alzheimer's disease : JAD
Volume90
Issue number1
DOIs
StatePublished - 2022

Keywords

  • Aging
  • Alzheimer’s disease
  • cancer
  • dementia
  • neuropathology
  • vascular disease

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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