@article{4a35875518714f128663d90b4c605671,
title = "Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample",
abstract = "Introduction 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. Discussion The impact of co-occurring pathologies on progression may depend on severity of ADNP.",
keywords = "Alzheimer's disease neuropathology, Cerebrovascular disease, Clinical progression, Lewy body disease, Mixed neuropathology",
author = "Brenowitz, {Willa D.} and Hubbard, {Rebecca A.} and Keene, {C. Dirk} and Hawes, {Stephen E.} and Longstreth, {W. T.} and Woltjer, {Randy L.} and Kukull, {Walter A.}",
note = "Funding Information: The NACC database is funded by National Institute on Aging/National Institutes of Health (NIA/NIH) Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI Marie-Francoise Chesselet, MD, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD). Pacific Northwest Dementia and Aging Neuropathology Group (PANDA) ADCs are supported by NIH P50 AG005136 (UW ADC) and NIH grants P30 AG008017, R01 AG024059, M01 RR000334, UL1 RR024140 as well as Intel Corporation and Department of Veterans Affairs (OHSU ADC).",
year = "2017",
month = jun,
doi = "10.1016/j.jalz.2016.09.015",
language = "English (US)",
volume = "13",
pages = "654--662",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "6",
}