Impact of multiple pathologies on the threshold for clinically overt dementia

Acta Neuropathol. 2017 Aug;134(2):171-186. doi: 10.1007/s00401-017-1717-7. Epub 2017 May 9.


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.

Keywords: Alzheimer’s disease; Biomarkers; Dementia; Mixed dementia; Mixed pathologies; Neuroimaging.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Cerebrovascular Disorders / complications
  • Cerebrovascular Disorders / diagnostic imaging
  • Cerebrovascular Disorders / pathology*
  • Cognition Disorders / etiology
  • Cohort Studies
  • Humans
  • Longitudinal Studies
  • Neuroimaging