title: Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample.
abstract: BACKGROUND
  Whether co-occurring neuropathologies interact or independently affect clinical disease progression is uncertain. We estimated rates of clinical progression and tested whether associations between clinical progression and Alzheimer's disease neuropathology (ADNP) were modified by co-occurring Lewy body disease (LBD) or vascular brain injury (VBI).
  
  
  METHODS
  Linear mixed effects models evaluated longitudinal trends in the Clinical Dementia Rating Scale Sum of Boxes on 2046 autopsied participants seen at a U.S. Alzheimer's Disease Center.
  
  
  RESULTS
  Annual clinical progression was slightly faster for ADNP + LBD compared with ADNP only (P = .06) and slightly slower for ADNP + VBI (P = .003). Differences in progression were less than expected if each neuropathology independently contributed to progression; ADNP interacted with LBD (P = .002) and VBI (P = .003). In secondary models, the effect of additional pathologies on clinical progression was greater in those with intermediate compared with high levels of ADNP.
  
  
  CONCLUSIONS
  The impact of co-occurring pathologies on progression may depend on severity of ADNP.
authors.affiliation: National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA. Electronic address: wbrenow@u.washington.edu.
authors.forename: Willa D
authors.initials: WD
authors.lastname: Brenowitz
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Hubbard
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Hawes
authors.affiliation: National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Longstreth
authors.affiliation: Department of Pathology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Woltjer
authors.affiliation: National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies
keywords: Alzheimer's disease neuropathology; Cerebrovascular disease; Clinical progression; Lewy body disease; Mixed neuropathology