Dataset Information

Most cases with Lewy pathology in a population-based cohort adhere to the Braak progression pattern but 'failure to fit' is highly dependent on staging system applied.

ABSTRACT: Braak et al.'s 2003 paper detailing the caudo-rostral progression of Lewy body pathology (LP) formed the foundation of current understanding of disease spread in Parkinson's disease (PD); however, its methods are difficult to recreate and consequently multiple new staging systems emerged to recapitulate Braak's staging system using standard neuropathological methods and to account for other patterns of LP. Studies using these systems have documented widely variable rates of cases that 'fail to fit' expected patterns of LP spread. This could be due to population differences, features of individual systems, or may constitute under-recognized patterns of disease. We examined 324 neuropathological cases from the Honolulu Asia Aging Study and applied four different LP staging systems to determine the proportion of cases adhering to different staging methodologies and those that 'fail to fit' expected patterns of LP. Of 141 cases with LP (24: PD, 8: Dementia with Lewy bodies (DLB), 109: Incidental Lewy body disease (ILBD)), our application of Braak et al., 2003 classified 83.7%, Müller et al., 2005 classified 87.9%, Beach et al., 2009 classified 100%, and Leverenz et al., 2008 classified 98.6%. There were significant differences in the cases classifiable by the Leverenz and Beach systems versus the Braak and Müller systems (p?

SUBMITTER: Coughlin DG

PROVIDER: S-EPMC6739131 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Most cases with Lewy pathology in a population-based cohort adhere to the Braak progression pattern but 'failure to fit' is highly dependent on staging system applied.

Coughlin David G DG Petrovitch Helen H White Lon R LR Noorigian Joseph J Masaki Kamal H KH Ross G Webster GW Duda John E JE

Parkinsonism & related disorders 20190328

Braak et al.'s 2003 paper detailing the caudo-rostral progression of Lewy body pathology (LP) formed the foundation of current understanding of disease spread in Parkinson's disease (PD); however, its methods are difficult to recreate and consequently multiple new staging systems emerged to recapitulate Braak's staging system using standard neuropathological methods and to account for other patterns of LP. Studies using these systems have documented widely variable rates of cases that 'fail to f ...[more]

PMID: 30948243

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Project description:The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P < 0.001). Analysis of Braak stages within age groups showed a significant increase in mid-Braak stages (III/IV), in middle age (40-65 years) compared with data from an ageing non-epilepsy series (P < 0.01). There was no clear relationship between seizure type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3% and cortical malformations in 11.3% were not significantly associated with Braak stage. Astrocytic-tau protein correlated with the presence of both traumatic brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis, identified in 40% (bilateral in 48%), was not associated with higher Braak stages, but asymmetrical patterns of tau protein accumulation within the sclerotic hippocampus were noted. In over half of patients with cognitive decline, the Braak stage was low indicating causes other than Alzheimer's disease pathology. In summary, there is evidence of accelerated brain ageing in severe chronic epilepsy although progression to high Braak stages was infrequent. Traumatic brain injury, but not seizures, was associated with tau protein accumulation in this series. It is likely that Alzheimer's disease pathology is not the sole explanation for cognitive decline associated with epilepsy.

Project description:BackgroundTo systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers of future cognitive decline in older adults with and without cognitive impairment.MethodsIn this longitudinal study, we included 396 cognitively normal to dementia subjects with 18F-Florbetapir/18F-Florbetaben-amyloid-PET, 18F-Flortaucipir-tau-PET and ~ 2-year cognitive follow-up. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. We determined global amyloid-PET (Centiloid) plus global and Braak-stage-specific tau-PET SUVRs, which were stratified as positive(+)/negative(-) at pre-established cut-offs, classifying subjects as Braak0/BraakI+/BraakI-IV+/BraakI-VI+/Braakatypical+. In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. Centiloid on subsequent cognitive decline. To test for independent tau vs. amyloid effects, analyses were further controlled for the contrary PET-tracer. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia.ResultsBaseline global tau-PET SUVRs explained more variance (partial R2) in future cognitive decline than Centiloid across all cognitive tests (Cohen's d ~ 2, all tests p < 0.001) and diagnostic groups. Associations between tau-PET and cognitive decline remained consistent when controlling for Centiloid, while associations between amyloid-PET and cognitive decline were non-significant when controlling for tau-PET. More advanced Braak-stage was associated with gradually worsening future cognitive decline, independent of Centiloid or diagnostic group (p < 0.001), and elevated conversion risk to MCI/dementia.ConclusionTau-PET and Braak-staging are highly predictive markers of future cognitive decline and may be promising single-modality estimates for prognostication of patient-specific progression risk in clinical settings.

Dataset Information

Most cases with Lewy pathology in a population-based cohort adhere to the Braak progression pattern but 'failure to fit' is highly dependent on staging system applied.

Publications

Most cases with Lewy pathology in a population-based cohort adhere to the Braak progression pattern but 'failure to fit' is highly dependent on staging system applied.

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