Open AccessRegional Multiple Pathology Scores Are Associated with Cognitive Decline in L ewy Body Dementias
Author(s) -
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 Tibor,
Francis Paul T.
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12182
Subject(s) - lewy body , dementia with lewy bodies , senile plaques , dementia , cognitive decline , neuroscience , neocortex , neurodegeneration , pathology , psychology , parahippocampal gyrus , cortex (anatomy) , temporal lobe , medicine , alzheimer's disease , disease , epilepsy
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 A lzheimer'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 ( BA 21, 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.