Impact of multiple pathologies on the threshold for clinically overt dementia

Alifiya Kapasi, Charles DeCarli, Julie A. Schneider

Research output: Contribution to journalReview articlepeer-review

200 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)171-186
Number of pages16
JournalActa Neuropathologica
Issue number2
StatePublished - Aug 1 2017


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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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