@article{92aef5752f7e44d096127eb2f94b083d,
title = "Neuropathological lesions and their contribution to dementia and cognitive impairment in a heterogeneous clinical population",
abstract = "Introduction: Alzheimer disease (AD) and related dementias are characterized by damage caused by neuropathological lesions in the brain. These include AD lesions (plaques and tangles) and non-AD lesions such as vascular injury or Lewy bodies. We report here an assessment of lesion association to dementia in a large clinic-based population. Methods: We identified 5272 individuals with neuropathological data from the National Alzheimer's Coordinating Center. Individual lesions, as well as a neuropathological composite score (NPCS) were tested for association with dementia, and both functional and neurocognitive impairment using regression models. Results: Most individuals exhibited mixed pathologies, especially AD lesions in combination with non-AD lesions. All lesion types were associated with one or more clinical outcomes; most even while controlling for AD pathology. The NPCS was also associated with clinical outcomes. Discussion: These data suggest mixed-type pathologies are extremely common in a clinic-based population and may contribute to dementia and cognitive impairment.",
keywords = "Alzheimer disease, Lewy bodies, amyloid angiopathy, cognitive decline, dementia, hippocampal sclerosis, neuritic plaques, neurofibrillary, neuropathology, tangles, vascular dementia",
author = "Dana Godrich and Martin, {Eden R.} and Gerard Schellenberg and Pericak-Vance, {Margaret A.} and Michael Cuccaro and Scott, {William K.} and Walter Kukull and Thomas Montine and Beecham, {Gary W.}",
note = "Funding Information: GS reports grant funding through the NIH and an honorarium from the BrightFocus Foundation for grant review. Funding Information: WKS reports grant funding through the NIH and an honorarium from the University of Chicago for speaking at a seminar. Funding Information: TM reports grant funding through the NIH and Farmer Family Foundation, royalty payments from UpToDate, honoraria and travel support for invited lectures, and has patents pending on novel chemical matter for treatment or imaging of neurodegenerative diseases. Funding Information: WK reports grant funding through the NIH, honoraria for serving on external advisory committees (Boston U ADRC, USC ADRC, UCI ADR, Mt. Sinai ADRC), honoraria for grant review (NIH: NIA/CSR), and travel support from the Alzheimer Association for participation in a symposium. Funding Information: This work was supported in part by the NIH National Institutes on Aging (grant number R01 AG062695). The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA‐funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428‐01 (PI James Leverenz, 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), P30 AG062421‐01 (PI Bradley Hyman, MD, PhD), P30 AG062422‐01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), 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), P30 AG062429‐01 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715‐01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association",
year = "2022",
doi = "10.1002/alz.12516",
language = "English (US)",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
}