Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important?
Yaroslau Compta,Laura Parkkinen,Sean S. O'Sullivan,Jana Vandrovcova,Janice L. Holton,Catherine A. Collins,Tammaryn Lashley,Constantinos Kallis,David R. Williams,David R. Williams,Rohan de Silva,Andrew J. Lees,Tamas Revesz +12 more
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TLDR
A combination ofLewy- and Alzheimer-type pathologies is a robust pathological correlate of dementia in Parkinson's disease, with quantitative and semi-quantitative assessment of Lewy pathology being more informative than Braak α-synuclein stages.Abstract:
The relative importance of Lewy- and Alzheimer-type pathologies to dementia in Parkinson's disease remains unclear. We have examined the combined associations of α-synuclein, tau and amyloid-β accumulation in 56 pathologically confirmed Parkinson's disease cases, 29 of whom had developed dementia. Cortical and subcortical amyloid-β scores were obtained, while tau and α-synuclein pathologies were rated according to the respective Braak stages. Additionally, cortical Lewy body and Lewy neurite scores were determined and Lewy body densities were generated using morphometry. Non-parametric statistics, together with regression models, receiver-operating characteristic curves and survival analyses were applied. Cortical and striatal amyloid-β scores, Braak tau stages, cortical Lewy body, Lewy neurite scores and Lewy body densities, but not Braak α-synuclein stages, were all significantly greater in the Parkinson's disease-dementia group (P<0.05), with all the pathologies showing a significant positive correlation to each other (P<0.05). A combination of pathologies [area under the receiver-operating characteristic curve=0.95 (0.88-1.00); P<0.0001] was a better predictor of dementia than the severity of any single pathology. Additionally, cortical amyloid-β scores (r=-0.62; P=0.043) and Braak tau stages (r=-0.52; P=0.028), but not Lewy body scores (r=-0.25; P=0.41) or Braak α-synuclein stages (r=-0.44; P=0.13), significantly correlated with mini-mental state examination scores in the subset of cases with this information available within the last year of life (n=15). High cortical amyloid-β score (P=0.017) along with an older age at onset (P=0.001) were associated with a shorter time-to-dementia period. A combination of Lewy- and Alzheimer-type pathologies is a robust pathological correlate of dementia in Parkinson's disease, with quantitative and semi-quantitative assessment of Lewy pathology being more informative than Braak α-synuclein stages. Cortical amyloid-β and age at disease onset seem to determine the rate to dementia.read more
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Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies
TL;DR: The spread of fibrillar α-synuclein pathology from the brainstem to limbic and neocortical structures seems to be the strongest neuropathological correlate of emerging dementia in Parkinson's disease.
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Cognitive decline in Parkinson disease
Dag Aarsland,Byron Creese,Byron Creese,Marios Politis,K. Ray Chaudhuri,Dominic Ffytche,Daniel Weintraub,Daniel Weintraub,Daniel Weintraub,Clive Ballard,Clive Ballard +10 more
TL;DR: New genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms.
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Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in Neurons
Jing L. Guo,Dustin J. Covell,Joshua P. Daniels,Michiyo Iba,Anna Stieber,Bin Zhang,Dawn M. Riddle,Linda K. Kwong,Yan Xu,John Q. Trojanowski,Virginia M.-Y. Lee +10 more
TL;DR: It is speculated that distinct strains of pathological α-synuclein likely exist in neurodegenerative disease brains and may underlie the tremendous heterogeneity of synucleinopathies.
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Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment
TL;DR: Preliminary findings show that imaging and neurophysiological and peripheral biomarkers could be useful in diagnosis and prognosis of Parkinson's disease, and emerging evidence suggests that memantine might also be useful.
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Neuropathologic substrates of Parkinson disease dementia.
David J. Irwin,Matthew T. White,Jon B. Toledo,Sharon X. Xie,John L. Robinson,Vivianna M. Van Deerlin,Virginia M.-Y. Lee,James B. Leverenz,Thomas J. Montine,John E. Duda,Howard I. Hurtig,John Q. Trojanowski +11 more
TL;DR: A study was undertaken to examine the neuropathological substrates of cognitive dysfunction and dementia in Parkinson disease (PD).
References
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“Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician
Marshal F. Folstein,Marshal F. Folstein,Susan E B Folstein,Susan E B Folstein,Paul R. McHugh,Paul R. McHugh +5 more
TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
A practical method for grading the cognitive state of patients for the clinician
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
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Staging of brain pathology related to sporadic Parkinson’s disease
TL;DR: This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
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What's wrong with Bonferroni adjustments
TL;DR: This paper advances the view, widely held by epidemiologists, that Bonferroni adjustments are, at best, unnecessary and, at worst, deleterious to sound statistical inference.
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