Summary Background Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and ...pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies. Methods In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of tau neurofibrillary tangles, neuritic plaques, α-synuclein inclusions, and other pathological changes in cortical regions. These samples were graded on an ordinal scale and genotyped for variants associated with synucleinopathies. We assessed the interval from onset of motor symptoms to onset of dementia, and overall survival in groups with varying levels of comorbid Alzheimer's disease pathology according to US National Institute on Aging–Alzheimer's Association neuropathological criteria, and used multivariate regression to control for age at death and sex. Findings On the basis of data from 213 patients who had been followed up to autopsy and met inclusion criteria of Lewy body disorder with autopsy-confirmed α synucleinopathy, we identified 49 (23%) patients with no Alzheimer's disease neuropathology, 56 (26%) with low-level Alzheimer's disease neuropathology, 45 (21%) with intermediate-level Alzheimer's disease neuropathology, and 63 (30%) with high-level Alzheimer's disease neuropathology. As levels of Alzheimer's disease neuropathology increased, cerebral α-synuclein scores were higher, and the interval between onset of motor and dementia symptoms and disease duration was shorter (p<0·0001 for all comparisons). Multivariate regression showed independent negative associations of cerebral tau neurofibrillary tangles score with the interval between onset of motor and dementia symptoms (β −4·0, 95% CI −5·5 to −2·6; p<0·0001; R2 0·22, p<0·0001) and with survival (–2·0, −3·2 to −0·8; 0·003; 0·15, <0·0001) in models that included age at death, sex, cerebral neuritic plaque scores, cerebral α-synuclein scores, presence of cerebrovascular disease, MAPT haplotype, and APOE genotype as covariates. Interpretation Alzheimer's disease neuropathology is common in synucleinopathies and confers a worse prognosis for each increasing level of neuropathological change. Cerebral neurofibrillary tangles burden, in addition to α-synuclein pathology and amyloid plaque pathology, are the strongest pathological predictors of a shorter interval between onset of motor and dementia symptoms and survival. Diagnostic criteria based on reliable biomarkers for Alzheimer's disease neuropathology in synucleinopathies should help to identify the most appropriate patients for clinical trials of emerging therapies targeting tau, amyloid-β or α synuclein, and to stratify them by level of Alzheimer's disease neuropathology. Funding US National Institutes of Health (National Institute on Aging and National Institute of Neurological Disorders and Stroke).
Despite the extensive use of complementary and alternative medicine (CAM) among cancer patients, patient-physician communication regarding CAM therapies remains limited. This study quantified the ...extent of patient-physician communication about CAM and identified factors associated with its discussion in radiation therapy (RT) settings.
We conducted a cross-sectional survey of 305 RT patients at an urban academic cancer center. Patients with different cancer types were recruited in their last week of RT. Participants self-reported their demographic characteristics, health status, CAM use, patient-physician communication regarding CAM, and rationale for/against discussing CAM therapies with physicians. Multivariate logistic regression was used to identify relationships between demographic/clinical variables and patients' discussion of CAM with radiation oncologists.
Among the 305 participants, 133 (43.6%) reported using CAM, and only 37 (12.1%) reported discussing CAM therapies with their radiation oncologists. In multivariate analyses, female patients (adjusted odds ratio AOR 0.45, 95% confidence interval CI 0.21-0.98) and patients with full-time employment (AOR 0.32, 95% CI 0.12-0.81) were less likely to discuss CAM with their radiation oncologists. CAM users (AOR 4.28, 95% CI 1.93-9.53) were more likely to discuss CAM with their radiation oncologists than were non-CAM users.
Despite the common use of CAM among oncology patients, discussions regarding these treatments occur rarely in the RT setting, particularly among female and full-time employed patients. Clinicians and patients should incorporate discussions of CAM to guide its appropriate use and to maximize possible benefit while minimizing potential harm.
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