Abstract Objective To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. Methods The ...clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. Results 172 cases were identified, of whom 143 (83%) were men. The mean ± SD age of onset in years for the core features were as follows – RBD, 62 ± 14 (range, 20–93), cognitive impairment ( n = 147); 69 ± 10 (range, 22–90), parkinsonism ( n = 151); 68 ± 9 (range, 20–92), and autonomic dysfunction ( n = 42); 62 ± 12 (range, 23–81). Death age was 75 ± 9 years (range, 24–96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10 ± 12 (range, 1–61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies ( n = 97), Parkinson’s disease with or without mild cognitive impairment or dementia ( n = 32), multiple system atrophy (MSA) ( n = 19), Alzheimer’s disease (AD)( n = 9) and other various disorders including secondary narcolepsy ( n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) ( n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)( n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD ( n = 59), MSA ( n = 19), AD ( n = 6), progressive supranulear palsy (PSP) ( n = 2), other mixed neurodegenerative pathologies ( n = 6), NBIA-1/LBD/tauopathy ( n = 1), and hypothalamic structural lesions ( n = 2). Among the neurodegenerative disorders associated with RBD ( n = 170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. Conclusions In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.
Aim: Understanding the relative importance of climatic and non-climatic distribution drivers for co-occurring, functionally similar species is required to assess potential consequences of climate ...change. This understanding is, however, lacking for most ecosystems. We address this knowledge gap and forecast changes in distribution for habitat-forming seaweeds in one of the world's most species-rich temperate reef ecosystems. Location: The Great Southern Reef. The full extent of Australia's temperate coastline. Methods: We assessed relationships between climatic and non-climatic environmental data known to influence seaweed, and the presence of 15 habitat-forming seaweeds. Distributional data (herbarium records) were analysed with MAXENT and generalized linear and additive models, to construct species distribution models at 0.2° spatial resolution, and project possible distribution shifts under the RCP 6.0 (medium) and 2.6 (conservative) emissions scenarios of ocean warming for 2100. Results: Summer temperatures, and to a lesser extent winter temperatures, were the strongest distribution predictors for temperate habitat-forming seaweeds in Australia. Projections for 2100 predicted major poleward shifts for 13 of the 15 species, on average losing 78% (range: 36%-100%) of their current distributions under RCP 6.0 and 62% (range: 27%-100%) under RCP 2.6. The giant kelp (Macrocystis pyrifera) and three prominent fucoids (Durvillaea potatorum, Xiphophora chondrophylla and Phyllospora comosa) were predicted to become extinct from Australia under RCP 6.0. Many species currently distributed up the west and east coasts, including the dominant kelp Ecklonia radiata (71% and 49% estimated loss for RPC 6.0 and 2.6, respectively), were predicted to become restricted to the south coast. Main conclusions: In close accordance with emerging observations in Australia and globally, our study predicted major range contractions of temperate seaweeds in coming decades. These changes will likely have significant impacts on marine biodiversity and ecosystem functioning because large seaweeds are foundation species for 100s of habitat-associated plants and animals, many of which are socio-economically important and endemic to southern Australia.
AUTHOR:e-mail address please Aim: To determine the incidence, regional variation in frequency, outcome, and risk factors for acanthamoeba keratitis (AK) in England and Wales. Methods: AK cases ...presenting from 1 October 1997 to 30 September 1999 were identified by the British Ophthalmic Surveillance Unit active reporting system. Clinical and patient postal questionnaire data were analysed. Results: 106 reported cases met study criteria. The annual incidence for the 2 years was 1.26 and 1.13 per million adults and, for contact lens (CL) wearers, 21.14 and 17.53 per million. There was marked regional variation in incidence (0 to 85.13 per million adult CL wearers), with CL wearers in the south having a ninefold increased risk of AK compared with those resident in the north (95% confidence limits: 2.2–38.9, p<0.0001), and a threefold increased risk with hard as opposed to soft domestic water (95% confidence limits: 1.73 to 6.58, p<0.001). Treatment and outcome data were similar to those previously reported. 93/106 (88%) patients were CL wearers. Among these, 46/77 (60%) were disinfecting irregularly, and 20/63 (32%) had been swimming in CLs. One step hydrogen peroxide and chlorine release soft CL (SCL) disinfection systems were significantly over-represented among the cases. Among SCL users, one or more previously established risk factors for AK were identified in 50/55 (91%) patients. Conclusions: The incidence was considerably higher than most previous estimates, and was static. The geographical variation in incidence may be partly related to the increase in risk associated with hard water. The fact that water quality can have such an effect on the risk of AK suggests that many CL wearers must be letting tapwater come into contact with their lenses or storage cases. Improved education for CL wearers and practitioners about hygiene practice and the variable efficacy of contact lens systems could be expected to reduce the incidence of this disease.
Sterile neutrinos are a minimal extension of the standard model of particle physics. A promising model-independent way to search for sterile neutrinos is via high-precision β-spectroscopy. The ...Karlsruhe tritium neutrino (KATRIN) experiment, equipped with a novel multi-pixel silicon drift detector focal plane array and read-out system, named the TRISTAN detector, has the potential to supersede the sensitivity of previous laboratory-based searches. In this work we present the characterization of the first silicon drift detector prototypes with electrons and we investigate the impact of uncertainties of the detector's response to electrons on the final sterile neutrino sensitivity.
Advances in ultrasensitive detection of phosphorylated tau (p-tau) in plasma has enabled the use of blood tests to measure Alzheimer's disease (AD) biomarker changes. Examination of postmortem brains ...of participants with antemortem plasma p-tau levels remains critical to understanding comorbid and AD-specific contribution to these biomarker changes.
We analyzed 35 population-based Mayo Clinic Study of Aging participants with plasma p-tau at threonine 181 and threonine 217 (p-tau181, p-tau217) available within 3 years of death. Autopsied participants included cognitively unimpaired, mild cognitive impairment, AD dementia, and non-AD neurodegenerative disorders. Global neuropathologic scales of tau, amyloid-β, TDP-43, and cerebrovascular disease were examined. Regional digital pathology measures of tau (phosphorylated threonine 181 and 217 pT181, pT217) and amyloid-β (6F/3D) were quantified in hippocampus and parietal cortex. Neurotransmitter hubs reported to influence development of tangles (nucleus basalis of Meynert) and amyloid-β plaques (locus coeruleus) were evaluated.
The strongest regional associations were with parietal cortex for tau burden (p-tau181 R = 0.55, p = 0.003; p-tau217 R = 0.66, p < 0.001) and amyloid-β burden (p-tau181 R = 0.59, p < 0.001; p-tau217 R = 0.71, p < 0.001). Linear regression analysis of global neuropathologic scales explained 31% of variability in plasma p-tau181 (Adj. R
= 0.31) and 59% in plasma p-tau217 (Adj. R
= 0.59). Neither TDP-43 nor cerebrovascular disease global scales independently contributed to variability. Global scales of tau pathology (β-coefficient = 0.060, p = 0.016) and amyloid-β pathology (β-coefficient = 0.080, p < 0.001) independently predicted plasma p-tau217 when modeled together with co-pathologies, but only amyloid-β (β-coefficient = 0.33, p = 0.021) significantly predicted plasma p-tau181. While nucleus basalis of Meynert neuron count/mm
was not associated with plasma p-tau levels, a lower locus coeruleus neuron count/mm
was associated with higher plasma p-tau181 (R = -0.50, p = 0.007) and higher plasma p-tau217 (R = -0.55, p = 0.002). Cognitive scores (Adj. R
= 0.25-0.32) were predicted by the global tau scale, but not by the global amyloid-β scale or plasma p-tau when modeled simultaneously.
Higher soluble plasma p-tau levels may be the result of an intersection between insoluble deposits of amyloid-β and tau accumulation in brain, and may be associated with locus coeruleus degeneration.
Alzheimer disease (AD) is neuropathologically classified into 3 corticolimbic subtypes based on the neurofibrillary tangle distribution throughout the hippocampus and association cortices: limbic ...predominant, typical, and hippocampal sparing. In vivo, a fourth subtype, dubbed "minimal atrophy," was identified using structural MRI. The objective of this study was to identify a neuropathologic proxy for the neuroimaging-defined minimal atrophy subtype.
We applied 2 strategies in the Florida Autopsied Multi-Ethnic (FLAME) cohort to evaluate a neuropathologic proxy for the minimal atrophy subtype. In the first strategy, we selected AD cases with a Braak tangle stage IV (Braak IV) because of the relative paucity of neocortical tangle involvement compared with Braak >IV. Braak IV cases were compared with the 3 AD subtypes. In the alternative strategy, typical AD was stratified by brain weight and cases having a relatively high brain weight (>75th percentile) were defined as minimal atrophy.
Braak IV cases (n = 37) differed from AD subtypes (limbic predominant n = 174, typical n = 986, and hippocampal sparing n = 187 AD) in having the least years of education (median 12 years, group-wise
< 0.001) and the highest brain weight (median 1,140 g,
= 0.002). Braak IV cases most resembled the limbic predominant cases owing to their high proportion of
ε4 carriers (75%,
< 0.001), an amnestic syndrome (100%,
< 0.001), as well as older age of cognitive symptom onset and death (median 79 and 85 years, respectively,
< 0.001). Only 5% of Braak IV cases had amygdala-predominant Lewy bodies (the lowest frequency observed,
= 0.017), whereas 32% had coexisting pathology of Lewy body disease, which was greater than the other subtypes (
= 0.005). Nearly half (47%) of the Braak IV samples had coexisting limbic predominant age-related TAR DNA-binding protein 43 encephalopathy neuropathologic change. Cases with a high brain weight (n = 201) were less likely to have amygdala-predominant Lewy bodies (14%,
= 0.006) and most likely to have Lewy body disease (31%,
= 0.042) compared with those with middle (n = 455) and low (n = 203) brain weight.
The frequency of Lewy body disease was increased in both neuropathologic proxies of the minimal atrophy subtype. We hypothesize that Lewy body disease may underlie cognitive decline observed in minimal atrophy cases.
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