Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Mixed Neuropathologies and Cognitive Decline Link

Neurology; ePub 2017 Sep 22; Brenowitz, et al

Alzheimer disease neuropathologic change (ADNC) + Lewy body disease (LBD) (but not ADNC + vascular brain injury [VBI]) was associated with poorer executive function and attention compared to other pathology groupings, according to a recent study. However, the effect of co-occurring pathologies on cognitive trajectories may depend on the severity of ADNC. Data came from 1,603 autopsied participants evaluated at US Alzheimer's Disease Centers. Standardized z scores in memory, attention, language, and executive function were derived from neuropsychological test scores assessed at each annual visit. Researchers found:

  • Compared to other participants, those with ADNC + LBD generally had worse cognitive trajectories, particularly lower initial executive function and faster attention decline.
  • Participants with ADNC + VBI typically had less impairment and slower decline.
  • Interactions were significant between LBD and ADNC for memory and between VBI and ADNC for language; decline was slower than expected if these neuropathologies acted additively on the rate of decline.
  • In secondary models, these interactions were limited to those with high ADNC (but not intermediate ADNC).


Brenowitz WD, Hubbard RA, Keene D, et al. Mixed neuropathologies and associations with domain-specific cognitive decline. [Published online ahead of print September 22, 2017]. Neurology. doi:10.1212/WNL.0000000000004567.

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