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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Infarcts typically are accompanied by Alzheimer disease and other pathologies.
“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]
The Introduction (page unavailable) says dementia, including probable AD, is often associated with mixed pathology involving AD, cerebral infarcts, and/or Lewy bodies. The Results and Discussion (pages unavailable) also report infarcts alongside mixed pathologies in community participants with probable AD. These passages support co-occurrence, but they do not establish the broader claim that infarcts are typically accompanied by AD and other pathologies. (LLM, conf=0.82)
Experimental — accuracy not yet measuredChronic macroscopic infarcts are very common, occurring in approximately one third to one half of older people, a frequency far greater than the frequency of clinical stroke.
“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]
The Results (Probable AD in the community versus clinic; page unavailable) report that macroscopic infarcts were more common in the community cohort than in the clinic cohort. The available passages do not establish that they occurred in one third to one half of older people or that their frequency was far greater than that of clinical stroke. (LLM, conf=0.81)
Experimental — accuracy not yet measuredInfarcts occur commonly in older people with and without dementia.
“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]
Experimental — accuracy not yet measuredInfarcts frequently coexist with Alzheimer disease pathology in the brains of older people.
“Infarcts frequently coexist with Alzheimer disease pathology in the brains of older people.”
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.
“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]
Studying individual cognitive trajectory captures all the factors affecting cognition, including diverse pathologies as well as biological mechanisms independent of pathologies.
“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]
Cognitive trajectory likely captures co-occurring disease processes and co-occurring age-related pathologies, which are known to be prevalent in the brains of aged individuals.
“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]
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.
“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]
In autopsy series associated with dementia clinics, a higher proportion of non-AD tauopathies are seen, presumably due to recruitment bias.
“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]
In most community-based autopsy series, non-AD tauopathies constitute approximately 1% of dementia cases.
“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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- 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
- Health Sciences › Medicine › Physiology › 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
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