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Impact of multiple pathologies on the threshold for clinically overt dementia

Abstract

Longitudinal clinical–pathological studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and cerebrovascular disease pathologies) as important factors in the development of Alzheimer’s disease (AD) and other forms of dementia. Older persons with AD pathology, often have concomitant cerebrovascular disease pathologies (macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy) as well as other concomitant neurodegenerative disease pathologies (Lewy bodies, TDP-43, hippocampal sclerosis). These additional pathologies lower the threshold for clinical diagnosis of AD. Many of these findings from pathologic studies, especially for CVD, have been confirmed using sophisticated neuroimaging technologies. In vivo biomarker studies are necessary to provide an understanding of specific pathologic contributions and time course relationships along the spectrum of accumulating pathologies. In this review, we provide a clinical–pathological perspective on the role of multiple brain pathologies in dementia followed by a review of the available clinical and biomarker data on some of the mixed pathologies.

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Acknowledgements

This study was funded by the US National Institutes of Health grants P30 AG10161, R01 AG17917, R01AG042210, and R01 AG022018. We are sincerely grateful to the participants enrolled in the Rush Memory and Aging Project, Rush Minority Aging Research Study, and Religious Orders Study Core. We thank the Rush Alzheimer’s Disease Center staff, in particular Karen Skish for laboratory management, John Gibbons for data management, Sue Leurgans for statistics, and Traci Colvin for study coordination of the cohorts.

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Correspondence to Julie A. Schneider.

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Kapasi, A., DeCarli, C. & Schneider, J.A. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol 134, 171–186 (2017). https://doi.org/10.1007/s00401-017-1717-7

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Keywords

  • Alzheimer’s disease
  • Dementia
  • Mixed dementia
  • Mixed pathologies
  • Neuroimaging
  • Biomarkers