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The Neuropathology of Older Persons with and Without Dementia from Community versus Clinic Cohorts
Open accessAbstract
Community-based cohorts of older persons may differ neuropathologically from clinic-based cohorts. This study investigated age-related pathologies in persons with and without dementia and included autopsied participants from two community-based cohorts, the Rush Religious Orders Study (n=386) and the Memory and Aging Project (n=195), and one clinic-based cohort, the Clinical Core of the Rush Alzheimer's Disease Center (n=392). Final clinical diagnoses included no cognitive impairment (n=202), mild cognitive impairment (MCI) (n=150), probable Alzheimer's disease (AD) (n=474), possible AD (n=88), and other dementias (n=59). Postmortem diagnoses included pathologic AD, cerebral infarcts, and Lewy body disease. Community-based persons with clinical AD had less severe AD pathology (p<0.001) and had more cerebral infarcts (p<0.001) compared to clinic-based persons. Additionally, community-based persons with MCI had more infarcts compared to clinic-based persons. Overall, there was a higher proportion of Lewy bodies and atypical pathologies in the clinic-based compared to the community-based cohorts (p<0.001). Community-based persons with probable AD show less severe AD pathology and more often have infarcts and mixed pathologies; those with MCI more often have infarcts and mixed pathologies. Overall, clinic-based persons have more Lewy bodies and atypical pathologies. The spectrum of pathologies underlying cognitive impairment in clinic-based cohorts differs from community-based cohorts.
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“typically are accompanied by Alzheimer disease and other pathologies.”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [54]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Chronic macroscopic infarcts are very common, occurring in approximately one third to one half of older people,13,54–56 a frequency far greater than the frequency of clinical stroke.”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [54]
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“In autopsy series associated with dementia clinics, a higher proportion of non-AD tauopathies are seen, presumably due to recruitment bias (111).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [111]
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“occur commonly in older people with and without dementia”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [54]
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“Infarcts frequently coexist with Alzheimer disease pathology in the brains of older people.”
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“It is widely recognized that clinic-based participants differ from community-based studies, for example, the amount, type, and distribution of neuropathologic changes differ by the source of a participant [206,207].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [206]
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“First, it captures all the factors affecting cognition, including diverse pathologies as well as biological mechanisms independent of pathologies4–6.”
From Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age (2019) · cites this paper as [4]
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“Second, it likely captures co-occurring disease processes and co-occurring age-related pathologies, which are known to be prevalent in the brains of aged individuals4,5.”
From Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age (2019) · cites this paper as [4]
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“For example, because persons with behavioral problems are more likely to require help than those with isolated memory problems, the prevalence and types of Lewy body disease derived from a clinic are likely to be different from those from a broader community (11).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [11]
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“In most community-based autopsy series, non-AD tauopathies constitute approximately 1% of dementia cases (108-115) (but see Noda et al [116]).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [111]
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Self-citationZammit, A. R., Yu, L., Oveisgharan, S., Schneider, J. A., Bennett, D. A., & Buchman, A. S. (2024) · The Journals of Gerontology Series A · doi:10.1093/gerona/glae275 · Cited by 3
Self-citationTodd, S., McGuinness, B., & Passmore, A. P. (2010) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2010.02490.x · Cited by 3
Diagnosis (2): Disorders Causing Dementia and Cognitive Impairment
Larner, A. J. (2018) · Springer eBooks · doi:10.1007/978-3-319-75259-4_9 · Cited by 3
Vascular Dementia and Cognitive Impairment
Seshadri, S. S., Caunca, M. R., & Rundek, T. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-69424-7.00018-1 · Cited by 3
Romero, K., Ladyka‐Wojcik, N., Heir, A. S., Bellana, B., Leach, L. R., & Proulx, G. B. (2022) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acac043 · Cited by 3
Nir, T. M., Haddad, E., Thompson, P. M., & Jahanshad, N. (2021) · Current topics in behavioral neurosciences · doi:10.1007/7854_2021_221 · Cited by 3
Vemuri, P., & Murray, M. E. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19041-4.00070-4 · Cited by 3
Broadening the scope of epidemiologic dementia research
Darweesh, S. K. L., Wolters, F. J., Ikram, M. A., Bos, D., & Albert Hofman, D. (2018) · European Journal of Epidemiology · doi:10.1007/s10654-018-0421-9 · Cited by 3
Vemuri, P., Jack, C. R., & Murray, M. E. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813955-4.00014-3 · Cited by 3
Baumgartner, N. W., Capuano, A. W., Barnes, L. L., Bennett, D. A. A., & Arvanitakis, Z. (2025) · medRxiv · doi:10.1101/2025.01.08.25320209 · Cited by 3
Self-citationSzum-Jakubowska, A., Chlabicz, M., Dubatówka, M., Stachurska, Z., Jamiołkowski, J., Teumer, A., Wittfeld, K., Hładuński, M., Kubas, B., Pawlak, M. A., et al. (2024) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.16825 · Cited by 2
Humanin variants aggregate to produce different fibril morphologies
Morris, D. L., Nyenhuis, S. B., Gruschus, J. M., Nyenhuis, D. A., Puja, R., Hinshaw, J. E., & Tjandra, N. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110403 · Cited by 2
Abbate, C., & Gallucci, A. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251374319 · Cited by 2
Cerebral amyloid angiopathy and Alzheimer's and related pathologies across APOE genotypes
Mehta, R. I., Wang, T., Leurgans, S. E., Bennett, D. A. A., & Schneider, J. A. (2026) · Brain · doi:10.1093/brain/awag025 · Cited by 3
Self-citationPost-stroke cognitive impairments: diagnosis and therapeutic approaches
Pizova, N. V. (2013) · Neurology neuropsychiatry Psychosomatics · doi:10.14412/2074-2711-2013-2360 · Cited by 2
Management of Mild Cognitive Impairment
Ravona‐Springer, R., & Korczyn, A. D. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190634230.003.0019 · Cited by 2
Decision Making and Blood Sugar Indicators in Older African American Adults
McSorley, V. E., Lamar, M., Yu, L., Bennett, D. A., Barnes, L. L., & Boyle, P. A. (2022) · Journal of Aging and Health · doi:10.1177/08982643221122639 · Cited by 2
Self-citationLange‐Maia, B. S., James, B. D., Capuano, A. W., Grodstein, F., Chen, Y., & Barnes, L. L. (2024) · The Journals of Gerontology Series A · doi:10.1093/gerona/glae089 · Cited by 2
Self-citationChange in transverse relaxation rates ( R2 ) and change in cognition for older African Americans
Lamar, M., Arfanakis, K., Capuano, A. W., Zhang, S., Fleischman, D. A., Han, S., Poole, V. N., Leurgans, S. E., Bennett, D. A., & Barnes, L. L. (2024) · Human Brain Mapping · doi:10.1002/hbm.26794 · Cited by 2
Self-citationChen, Y., James, B. D., Capuano, A. W., Banerjee, M., Springer, M. V., Lange‐Maia, B. S., Barnes, L. L., Bennett, D. A., Bynum, J., & Grodstein, F. (2025) · Journal of the American Geriatrics Society · doi:10.1111/jgs.19446 · Cited by 3
Self-citationWhite, L. R. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-111269 · Cited by 2
Dickie, D. A., Quinn, T. J., & Dawson, J. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-31904-5_3 · Cited by 3
Weight loss in a cardiovascular trial population identifies people at future risk of dementia
van der Veere, P. J., Hammami, I., Buck, G. A. N., Greenland, M., Offer, A. R., Nunn, M., Whiteley, W. N., Bulbulia, R. A., Collins, R., Armitage, J., et al. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12352 · Cited by 2
Dementia and Cognitive Impairment
Chong, Y. F. V., & Tang, S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99967-0.00134-4 · Cited by 2
Barsoum, S., Latimer, C. S., Nolan, A., Barrett, A., Chang, K., Troncoso, J. C., Keene, C. D., & Benjamini, D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.06.592719 · Cited by 2
Excess deaths due to incident Alzheimer’s dementia in women and men in the United StatesPreprint
James, B. D., Wang, T., Leurgans, S. E., Barnes, L. L., Márquez, D. X., & Bennett, D. A. (2025) · medRxiv · doi:10.1101/2025.08.27.25334590 · Cited by 2
Self-citationMajor or Mild Vascular Neurocognitive Disorder
Espiritu, A. I., Balakrishnar, K., Moradizadeh, M., Marlatt, N. E., & Burhan, A. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-47802-4_21 · Cited by 1
Social factors associated with everyday functioning in older Black adults
Davis, K., & Calamia, M. R. (2025) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617725000037 · Cited by 1
The association of mild cognitive impairment with outpatient visits for hypertension
Springer, M. V., Chen, Y., Benloucif, S., Grodstein, F., James, B. D., Capuano, A. W., Banerjee, M., & Bynum, J. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70743 · Cited by 1
Metadata
- Authors
- Schneider, J. A., Aggarwal, N. T., Barnes, L., Boyle, P., & Bennett, D. A.
- Affiliations
- Rush University Medical Center (US)
- Corresponding author
- Schneider, Julie A.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2009-10-30
- Volume
- 18
- Issue
- 3
- Pages
- 691-701
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC2853869
- OpenAlex
- W1548995643
- Cited by
- 372
- References
- 34
- Citations by year
- 2026: 27 · 2025: 28 · 2024: 24 · 2023: 16 · 2022: 27 · 2021: 21 · 2020: 19 · 2019: 20 · 2018: 20 · 2017: 24 · 2016: 24 · 2015: 17 · 2014: 18 · 2013: 24 · 2012: 18
- FWCI
- 12.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG017917, K08 AG00849, P30-AG 10161, R01‐AG17917, R01 AG15819, R01AG015819, P30AG010161, K08AG000849, R01AG022018)
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- neuropathology, dementia
- MeSH terms
- Aged, Aging, Alzheimer Disease, Cognition Disorders, Community Health Services, Dementia, Humans, Memory Disorders, Neuropsychological Tests, Severity of Illness Index, Tissue Donors, Cohort Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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