Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias

David R. Howlett, David Whitfield, Mary Johnson, Johannes Attems, John T. O'Brien, Dag Aarsland, Mitchell K P Lai, Jasinda H. Lee, Christopher Chen, Clive Ballard, T. Hortobágyi, Paul T. Francis

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.

Original languageEnglish
Pages (from-to)401-408
Number of pages8
JournalBrain Pathology
Volume25
Issue number4
DOIs
Publication statusPublished - Jul 1 2015

Fingerprint

Lewy Body Disease
Synucleins
Dementia
Pathology
Amyloid Plaques
Neocortex
Temporal Lobe
Cognition
Parkinson Disease
Lewy Bodies
Neurofibrillary Tangles
Neurites
Prefrontal Cortex
Cognitive Dysfunction
Alzheimer Disease
Regression Analysis

Keywords

  • Alzheimer's disease
  • cognitive decline
  • dementia with Lewy bodies
  • Lewy body dementia
  • Parkinson's disease dementia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Howlett, D. R., Whitfield, D., Johnson, M., Attems, J., O'Brien, J. T., Aarsland, D., ... Francis, P. T. (2015). Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias. Brain Pathology, 25(4), 401-408. https://doi.org/10.1111/bpa.12182

Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias. / Howlett, David R.; Whitfield, David; Johnson, Mary; Attems, Johannes; O'Brien, John T.; Aarsland, Dag; Lai, Mitchell K P; Lee, Jasinda H.; Chen, Christopher; Ballard, Clive; Hortobágyi, T.; Francis, Paul T.

In: Brain Pathology, Vol. 25, No. 4, 01.07.2015, p. 401-408.

Research output: Contribution to journalArticle

Howlett, DR, Whitfield, D, Johnson, M, Attems, J, O'Brien, JT, Aarsland, D, Lai, MKP, Lee, JH, Chen, C, Ballard, C, Hortobágyi, T & Francis, PT 2015, 'Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias', Brain Pathology, vol. 25, no. 4, pp. 401-408. https://doi.org/10.1111/bpa.12182
Howlett DR, Whitfield D, Johnson M, Attems J, O'Brien JT, Aarsland D et al. Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias. Brain Pathology. 2015 Jul 1;25(4):401-408. https://doi.org/10.1111/bpa.12182
Howlett, David R. ; Whitfield, David ; Johnson, Mary ; Attems, Johannes ; O'Brien, John T. ; Aarsland, Dag ; Lai, Mitchell K P ; Lee, Jasinda H. ; Chen, Christopher ; Ballard, Clive ; Hortobágyi, T. ; Francis, Paul T. / Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias. In: Brain Pathology. 2015 ; Vol. 25, No. 4. pp. 401-408.
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