Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample
Open accessAbstract
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.
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Some studies report that the majority of people with the brain changes of Alzheimer's disease also have the brain changes of a second cause of dementia on autopsy.
“Some studies report that the majority of people with the brain changes of Alzheimer's disease also have the brain changes of a second cause of dementia on autopsy.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [22]
The Introduction (page unavailable) reports that up to 75% of autopsied older adults have multiple brain pathologies, and the Results §3.1 (page unavailable) say that Alzheimer’s pathology commonly co-occurred with Lewy body disease or vascular brain injury at autopsy. Neither passage establishes that a majority of people specifically with Alzheimer’s pathology had a second pathology; the 75% figure applies to autopsied older adults overall. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCognitive trajectories were similar between participants with mixed pathologies and participants who only had ADNC; impact of co-occurring pathologies may have been due to severity of AD more than mixed pathologies.
“Other studies found that cognitive trajectories were similar between participants with mixed pathologies and participants who only had ADNC; though, the impact of co-occurring pathologies may have been due to the severity of AD more than the mixed pathologies (18,19).”
From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [19]
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- Authors
- Brenowitz, W. D., Hubbard, R. A., Keene, C. D., Hawes, S. E., Longstreth, W. T., Woltjer, R. L., & Kukull, W. A.
- Affiliations
- University of Washington (US)
- University of Pennsylvania (US)
- Oregon Health & Science University (US)
- Corresponding author
- Brenowitz, Willa D.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-11-18
- Volume
- 13
- Issue
- 6
- Pages
- 654-662
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5438283
- OpenAlex
- W2556839390
- Cited by
- 188
- References
- 58
- Citations by year
- 2026: 20 · 2025: 21 · 2024: 22 · 2023: 51 · 2022: 19 · 2021: 15 · 2020: 14 · 2019: 11 · 2018: 8 · 2017: 5 · 2016: 1
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P30 AG008017, P30 AG010161, P50 AG047366, P30 AG010129, P50 AG016573, P50 AG016570, P50 AG005131, P50 AG023501, P30 AG035982, P30 AG028383, P30 AG010124, P50 AG005133, P50 AG005142, P30 AG012300, P50 AG005136, P50 AG033514, P50 AG005681, P50 AG047270)
- National Institutes of Health
- National Association for Colitis and Crohn's Disease
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease pathology, Lewy body disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Brain, Cerebrovascular Disorders, Female, Humans, Longitudinal Studies, Male, Prospective Studies, Multivariate Analysis, Linear Models, Disease Progression, Lewy Body Disease
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