Mixed neuropathologies and associations with domain-specific cognitive decline

Willa D. Brenowitz, Rebecca A. Hubbard, C. Dirk Keene, Stephen E. Hawes, W. T. Longstreth, Randall (Randy) Woltjer, Walter A. Kukull

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: To test whether decline in specific cognitive domains associated with Alzheimer disease neuropathologic change (ADNC) is modified by co-occurrence of other neuropathologies such as Lewy body disease (LBD) or vascular brain injury (VBI). Methods: 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. Multivariable linear mixed-effects models assessed associations between neuropathologies and longitudinal trajectories of domain scores. Results: Compared to other participants, those with ADNC 1 LBD generally had worse cognitive trajectories, particularly lower initial executive function and faster attention decline. Participants with ADNC 1 VBI typically had less impairment and slower decline. Interactions were significant between LBD and ADNC for memory (p 5 0.046) and between VBI and ADNC for language (p 5 0.03); 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). In a subset of 260 participants with data on microinfarct location, cortical and subcortical microinfarcts were associated with decline in memory, language, and executive function in those without ADNC, but this effect was reduced among those with ADNC.

Original languageEnglish (US)
Pages (from-to)1773-1781
Number of pages9
JournalNeurology
Volume89
Issue number17
DOIs
StatePublished - Oct 24 2017
Externally publishedYes

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Alzheimer Disease
Cerebrovascular Trauma
Lewy Body Disease
Executive Function
Language
Neuropathology
Cognitive Dysfunction
Neuropsychological Tests
Brain Diseases

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Brenowitz, W. D., Hubbard, R. A., Keene, C. D., Hawes, S. E., Longstreth, W. T., Woltjer, R. R., & Kukull, W. A. (2017). Mixed neuropathologies and associations with domain-specific cognitive decline. Neurology, 89(17), 1773-1781. https://doi.org/10.1212/WNL.0000000000004567

Mixed neuropathologies and associations with domain-specific cognitive decline. / Brenowitz, Willa D.; Hubbard, Rebecca A.; Keene, C. Dirk; Hawes, Stephen E.; Longstreth, W. T.; Woltjer, Randall (Randy); Kukull, Walter A.

In: Neurology, Vol. 89, No. 17, 24.10.2017, p. 1773-1781.

Research output: Contribution to journalArticle

Brenowitz, WD, Hubbard, RA, Keene, CD, Hawes, SE, Longstreth, WT, Woltjer, RR & Kukull, WA 2017, 'Mixed neuropathologies and associations with domain-specific cognitive decline', Neurology, vol. 89, no. 17, pp. 1773-1781. https://doi.org/10.1212/WNL.0000000000004567
Brenowitz WD, Hubbard RA, Keene CD, Hawes SE, Longstreth WT, Woltjer RR et al. Mixed neuropathologies and associations with domain-specific cognitive decline. Neurology. 2017 Oct 24;89(17):1773-1781. https://doi.org/10.1212/WNL.0000000000004567
Brenowitz, Willa D. ; Hubbard, Rebecca A. ; Keene, C. Dirk ; Hawes, Stephen E. ; Longstreth, W. T. ; Woltjer, Randall (Randy) ; Kukull, Walter A. / Mixed neuropathologies and associations with domain-specific cognitive decline. In: Neurology. 2017 ; Vol. 89, No. 17. pp. 1773-1781.
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