Neuropathology-Based Risk Scoring for Dementia Diagnosis in the Elderly
Open accessAbstract
Current neuropathologic consensus criteria for diagnosis of dementia yield a classification of processes that likely contributed to dementia in that individual. While dementia diagnosis currently relies on clinical criteria, practicing neuropathologists and researchers might benefit from a simple, accurate risk scoring protocol for the neuropathologic diagnosis of dementia. Using 232 consecutive autopsies from the population-based Adult Changes in Thought study, we developed two logistic regression-based risk scoring systems; one solely using neuropathologic measures and a second additionally including demographic information. Inverse-probability weighting was used to adjust for inherent selection bias in autopsy-based studies of dementing illnesses. Both systems displayed high levels of predictive accuracy; bias-adjusted area-under-the-curve statistics were 0.78 (95% CI 0.71, 0.85) and 0.87 (95% CI 0.83, 0.92), indicating improved performance with the inclusion of demographic characteristics, specifically age and birth cohort information. Application of the combined neuropathology/demographic model yielded bias-adjusted sensitivity and specificity of 81% each. In contrast, application of NIA-Reagan criteria yielded sensitivity and specificity of 53% and 84%. Our proposed scoring systems provide neuropathologists with tools to make a diagnosis, and interpret their diagnosis in the light of known sensitivity and specificity estimates. Evaluation in independent samples will be important to verify our findings.
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Although the specific importance of subcortical infarcts and interaction has not been confirmed, subsequent studies have established that infarcts are additive with Alzheimer disease pathology in lowering cognitive function and increasing the odds of dementia or clinical Alzheimer disease.
“Although the specific importance of subcortical infarcts and interaction has not been confirmed, subsequent studies have established that infarcts are additive with Alzheimer disease pathology in lowering cognitive function17,57 and increasing the odds of dementia17,18,62,63 or clinical Alzheimer disease.61”
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 [62]
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Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
The Elements of Statistical Learning
Hastie, T., Tibshirani, R., & Friedman, J. (2009) · Springer Series in Statistics · doi:10.1007/978-0-387-84858-7 · Cited by 25,970 · see citing works
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056 · see citing works
The Statistical Evaluation of Medical Tests for Classification and Prediction
PEPE, M. S. (2005) · Technometrics · doi:10.1198/tech.2005.s278 · Cited by 1,907 · see citing works
HYMAN, B. T., & TROJANOWSKI, J. Q. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199710000-00002 · Cited by 1,542 · see citing works
Subcortical ischaemic vascular dementia
Román, G. C., Erkinjuntti, T., Wallin, A., Pantoni, L., & Chui, H. C. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00190-4 · Cited by 1,067 · see citing works
Teng, E. L., Hasegawa, K., Homma, A., Imai, Y., Larson, E. B., Graves, A. B., Sugimoto, K., Yamaguchi, T., Sasaki, H., Chiu, D., et al. (1994) · International Psychogeriatrics · doi:10.1017/s1041610294001602 · Cited by 910 · see citing works
Self-citationDementia and Alzheimer Disease Incidence: A Prospective Cohort Study
Kukull, W. A., Higdon, R., Bowen, J. D., McCormick, W. C., Teri, L., Schellenberg, G. D., van Belle, G., Jolley, L., & Larson, E. B. (2002) · Archives of Neurology · doi:10.1001/archneur.59.11.1737 · Cited by 806 · see citing works
Self-citationNeuropathology of Cognitively Normal Elderly
Knopman, D. S., Parisi, J. E., Salviati, A., Floriach-Robert, M., Boeve, B. F., Ivnik, R. J., Smith, G. E., Dickson, D. W., Johnson, K. A., Petersen, L. E., et al. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.11.1087 · Cited by 674 · see citing works
Utility of the Apolipoprotein E Genotype in the Diagnosis of Alzheimer's Disease
Mayeux, R., Saunders, A. M., Shea, S., Mirra, S., Evans, D., Roses, A. D., Hyman, B. T., Crain, B., Tang, M.-X., & Phelps, C. H. (1998) · New England Journal of Medicine · doi:10.1056/nejm199802193380804 · Cited by 547 · see citing works
Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions
Bennett, D. A., Schneider, J. A., Bienias, J. L., Evans, D. A., & Wilson, R. S. (2005) · Neurology · doi:10.1212/01.wnl.0000152982.47274.9e · Cited by 537 · see citing works
Alzheimer neuropathologic alterations in aged cognitively normal subjects
Davis, D. G., Schmitt, F. A., Wekstein, D. R., & Markesbery, W. R. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199904000-00008 · Cited by 516 · cited 1× · see citing works
“Others have also evaluated the performance of the NIA-Reagan criteria with similar results [8,12-16].”
Pathological correlates of dementia in a longitudinal, population‐based sample of aging
Sonnen, J. A., Larson, E. B., Crane, P. K., Haneuse, S., Li, G., Schellenberg, G. D., Craft, S., Leverenz, J. B., & Montine, T. J. (2007) · Annals of Neurology · doi:10.1002/ana.21208 · Cited by 432 · see citing works
Self-citationCerebrovascular Pathology and Dementia in Autopsied Honolulu‐Asia Aging Study Participants
WHITE, L., PETROVITCH, H., HARDMAN, J., NELSON, J., DAVIS, D. G., ROSS, G. W., MASAKI, K., LAUNER, L., & MARKESBERY, W. R. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04794.x · Cited by 357 · see citing works
Towards defining the neuropathological substrates of vascular dementia
Kalaria, R. N., Kenny, R. A., Ballard, C. G., Perry, R., Ince, P., & Polvikoski, T. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.09.019 · Cited by 291 · see citing works
Newell, K. L., Hyman, B. T., Growdon, J. H., & Hedley-Whyte, E. T. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199911000-00004 · Cited by 289 · see citing works
Combining Several Screening Tests: Optimality of the Risk Score
McIntosh, M. W., & PEPE, M. S. (2002) · Biometrics · doi:10.1111/j.0006-341x.2002.00657.x · Cited by 254 · see citing works
AD lesions and infarcts in demented and non‐demented Japanese‐American men
Petrovitch, H., Ross, G. W., Steinhorn, S. C., Abbott, R. D., Markesbery, W., Davis, D., Nelson, J., Hardman, J., Masaki, K., Vogt, M. R., et al. (2005) · Annals of Neurology · doi:10.1002/ana.20318 · Cited by 230 · see citing works
. Identification of Alzheimer and vascular lesion thresholds for mixed dementia.
Gold, G., Giannakopoulos, P., Herrmann, F. R., Bouras, C., & Kovari, E. (2007) · Brain · doi:10.1093/brain/awm228 · Cited by 163 · see citing works
White, L., Small, B. J., Petrovitch, H., Ross, G. W., Masaki, K., Abbott, R. D., Hardman, J., Davis, D., Nelson, J., & Markesbery, W. (2005) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988705281872 · Cited by 155 · see citing works
Prevalence of dementia subtypes: A 30-year retrospective survey of neuropathological reports
Brunnström, H., Gustafson, L., Passant, U., & Englund, E. M. (2008) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2008.06.005 · Cited by 148 · see citing works
Clinicopathological analysis of dementia disorders in the elderly – An update
Jellinger, K. A. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s308 · Cited by 143 · see citing works
ZACCAI, J. H., Ince, P. G., & Brayne, C. (2006) · BMC Neurology · doi:10.1186/1471-2377-6-2 · Cited by 111 · see citing works
Haneuse, S., Schildcrout, J. S., Crane, P. K., Sonnen, J. A., Breitner, J. C. S., & Larson, E. B. (2009) · Neuroepidemiology · doi:10.1159/000197389 · Cited by 106 · see citing works
Self-citationComparison of neuropathologic criteria for the diagnosis of Alzheimer's disease
Geddes, J. W., Tekirian, T. L., Soultanian, N. S., Ashford, J. W., Davis, D. G., & Markesbery, W. R. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00063-8 · Cited by 101 · see citing works
University of Washington Alzheimer's Disease Patient Registry (ADPR): 1987-1988.
Larson, E. B., Kukull, W. A., Teri, L. L., McCormick, W. C., Pfanschmidt, M. L., van Belle, G., & Sumi, M. (1990) · PubMed · Cited by 68 · see citing works
Self-citationSimplified neuropathological diagnosis of dementia with Lewy bodies
Harding, Harding, Halliday, et al. (1998) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.1998.00115.x · Cited by 46 · see citing works
Tsuang, D., Larson, E. B., Bowen, J., McCormick, W., Teri, L., Nochlin, D., Leverenz, J. B., Peskind, E. R., Lim, A., Raskind, M. A., et al. (1999) · Archives of Neurology · doi:10.1001/archneur.56.12.1489 · Cited by 42 · see citing works
Self-citationSurgical Pathologic Findings of Extratemporal-Based Intractable Epilepsy
Vinters, H. V. (2000) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2000-124-1111-spfoeb · Cited by 40 · see citing works
What is aging? What is its role in Alzheimer's disease? What can we do about it?
Ashford, J., Atwood, C., Blass, J., Bowen, R., Finch, C., Iqbal, K., Joseph, J., & Perry, G. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7308 · Cited by 25 · see citing works
Cochran, E. J., Schneider, J. A., Bennett, D., et al. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199805000-00175 · Cited by 7 · see citing works
Harrell, F., Jr. (1996) · doi:10.1002/(sici)1097-0258(19960229)15:4
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Cited by
Sorted by citations
Gorelick, P. B., Scuteri, A., Black, S. E., DeCarli, C., Greenberg, S. M., Iadecola, C., Launer, L. J., Laurent, S., Lopez, O. L., Nyenhuis, D., et al. (2011) · Stroke · doi:10.1161/str.0b013e3182299496 · Cited by 3,811 · see citing works
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · see citing works
Self-citationBeach, T. G., Monsell, S. E., Phillips, L. E., & Kukull, W. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31824b211b · Cited by 1,103 · see citing works
Integrated multimodal cell atlas of Alzheimer’s disease
Gabitto, M. I., Travaglini, K. J., Rachleff, V. M., Kaplan, E. S., Long, B., Ariza, J., Ding, Y., Mahoney, J. T., Dee, N., Goldy, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01774-5 · Cited by 397 · see citing works
Self-citation
- Authors
- Haneuse, S., Larson, E., Walker, R., Montine, T., & Sonnen, J.
- Affiliations
- Group Health Cooperative (US)
- University of Washington (US)
- Corresponding author
- Haneuse, Sebastien
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2009-07-23
- Volume
- 17
- Issue
- 4
- Pages
- 875-885
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC2852462
- OpenAlex
- W2152207212
- Cited by
- 15
- References
- 33
- Citations by year
- 2024: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2015: 2 · 2013: 2 · 2012: 2
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (3r01ag002380-06s1)
- National Institute on Aging (U01-AG-06781, U01AG006781, R01 AG02380, R01AG023801)
- 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
- dementia diagnosis, neuropathology
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Autopsy, Brain, Dementia, Female, Humans, Male, Sensitivity and Specificity, Sex Factors, Dementia, Vascular, Bias, Confidence Intervals
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