Clinicopathological Correlations and Concomitant Pathologies in Rapidly Progressive Dementia: A Brain Bank Series

Neurodegener Dis. 2015;15(6):350-60. doi: 10.1159/000439251. Epub 2015 Oct 31.

Abstract

Background: Rapidly progressive dementia (RPD) is caused by a heterogeneous group of both neurodegenerative and non-neurodegenerative disorders. The presence of concomitant pathologies, mainly Alzheimer's disease (AD), may act as a confounding variable in the diagnostic process of this group of diseases.

Objectives: We aimed to describe clinicopathological features, including Alzheimer's co-pathology, and diagnostic accuracy in a postmortem series of RPD.

Methods: Retrospective analysis of 160 brain donors with RPD (defined as 2 years of disease duration from the first symptom to death) registered at the Neurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS, from 2001 to 2011.

Results: Prion diseases were the most frequent neuropathological diagnosis (67%), followed by non-prion neurodegenerative pathologies (17%), mostly AD and dementia with Lewy bodies, and non-neurodegenerative diseases (16%). We observed clinicopathological diagnostic agreement in 94% of the patients with prion RPD but only in 21% of those with non-prion RPD. Four patients with potentially treatable disorders were diagnosed, while still alive, as having Creutzfeldt-Jakob disease. Concomitant pathologies were detected in 117 (73%). Among all RPD cases, 51 presented moderate or frequent mature β-amyloid plaques (neuritic plaques), which are considered to be associated with positive amyloid biomarkers in vivo.

Conclusions: Prion diseases were accurately identified in our series. In contrast, non-prion RPD diagnosis was poor while the patients were still alive, supporting the need for better diagnostic tools and confirmatory neuropathological studies. The presence of concomitant AD pathology in RPD should be taken into account in the interpretation of amyloid biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / pathology*
  • Amyloid / metabolism*
  • Brain / pathology*
  • Creutzfeldt-Jakob Syndrome / diagnosis
  • Creutzfeldt-Jakob Syndrome / pathology*
  • Diagnosis, Differential
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prions / metabolism*
  • Retrospective Studies
  • Young Adult

Substances

  • Amyloid
  • Prions