Alzheimer's disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods ...integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer's disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer's disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer's disease and cognitively normal subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer's Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer's disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.
Parkinson's disease (PD) is a chronic, progressive, complex movement disorder. In addition to the motor manifestations, changes in mood and cognition frequently occur. It is understandable that ...receiving this diagnosis can be difficult for patients and their significant others. For the clinician, delivering a PD diagnosis can be challenging and requires a comprehensive patient assessment followed by a thoughtful treatment plan. How this diagnosis is conveyed can have a long-term impact on patient outcomes such as treatment adherence, participation in decision making, understanding of PD, and satisfaction with care. Because a PD diagnosis is often complicated by uncertainty about the diagnosis itself as well as future prognosis, a sensitive patient-centered approach to care, balanced with realistic expectations, is recommended. Full disclosure, honesty, and empathy on the part of the entire healthcare team are required. This includes relevant information tailored to the patient's unique needs at the time of diagnosis as well as referrals to appropriate rehabilitation and support services. Consistent, timely follow-up of all interventions is essential. It is essential that a diagnosis of PD is properly delivered to optimize understanding of PD, treatment adherence, participation in decision making, and satisfaction with care. In this article, we provide guidance on delivery of this diagnosis based on a growing body of evidence and our >35-year collective clinical experience and work developing and utilizing pertinent, creative educational tools and comprehensive, sensitive support programs for newly diagnosed patients and their significant others. Although most of the evidence we present pertains to PD, our experience suggests it could also apply to other forms of Parkinsonism and other chronic or progressive movement disorders.
Advances in medical management of Parkinson's disease (PD) have resulted in living longer with disability. Although disability worsens over the course of the disease, there are signs of disability ...even in the early stages. Several studies reveal an early decline in gait and balance and a high prevalence of nonmotor signs in the prodromal period that contribute to early disability. There is a growing body of evidence revealing the benefits of physical therapy and exercise to mitigate motor and nonmotor signs while improving physical function and reducing disability. The presence of early disability coupled with the benefits of exercise suggests that physical therapy should be initiated earlier in the disease. In this review, we present the evidence revealing early disability in PD and the effectiveness of physical therapy and exercise, followed by a discussion of a secondary prevention model of rehabilitation to reduce early disability and optimize long-term outcomes.
Shared decision making (SDM) is a process whereby decisions are made together by patients and/or families and clinicians. Nevertheless, few patients are aware of its proven benefits. This study ...investigated the feasibility, acceptability and impact of an intervention to raise public awareness of SDM in public libraries.
A 1.5 hour interactive workshop to be presented in public libraries was co-designed with Quebec City public library network officials, a science communication specialist and physicians. A clinical topic of maximum reach was chosen: antibiotic overuse in treatment of acute respiratory tract infections. The workshop content was designed and a format, whereby a physician presents the information and the science communication specialist invites questions and participation, was devised. The event was advertised to the general public. An evaluation form was used to collect data on participants' sociodemographics, feasibility and acceptability components and assess a potential impact of the intervention. Facilitators held a post-workshop focus group to qualitatively assess feasibility, acceptability and impact.
All 10 planned workshops were held. Out of 106 eligible public participants, 89 were included in the analysis. Most participants were women (77.6%), retired (46.1%) and over 45 (59.5%). Over 90% of participants considered the workshop content to be relevant, accessible, and clear. They reported substantial average knowledge gain about antibiotics (2.4, 95% Confidence Interval (CI): 2.0-2.8; P < .001) and about SDM (4.0, 95% CI: 3.4-4.5; P < .001). Self-reported knowledge gain about SDM was significantly higher than about antibiotics (4.0 versus 2.4; P < .001). Knowledge gain did not vary by sociodemographic characteristics. The focus group confirmed feasibility and suggested improvements.
A public library intervention is feasible and effective way to increase public awareness of SDM and could be a new approach to implementing SDM by preparing potential patients to ask for it in the consulting room.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The occupational therapy intervention might not have focused on aspects of Parkinson's disease that become problematic for both caregivers and their patients in more advanced disease, such as ...cognitive deficits, other non-motor symptoms, and social isolation. Findings have shown that social concerns are a primary focus for individuals with Parkinson's disease and their caregivers and that disease symptoms and social aspects of self-care are inter-related.5 Typically, physical therapy and occupational therapy in Parkinson's disease have been prescribed when patients become substantially disabled.
Background: Research using reconstructed exposure histories has suggested an association between heavy metal exposures, including lead, and Parkinson's disease (PD), but the only study that used bone ...lead, a biomarker of cumulative lead exposure, found a nonsignificant increase in risk of PD with increasing bone lead. Objectives: We sought to assess the association between bone lead and PD. Methods: Bone lead concentrations were measured using ¹⁰⁹Cd excited K-shell X-ray fluorescence from 330 PD patients (216 men, 114 women) and 308 controls (172 men, 136 women) recruited from four clinics for movement disorders and general-community cohorts. Adjusted odds ratios (ORs) for PD were calculated using logistic regression. Results: The average age of cases and controls at bone lead measurement was 67 (SD = 10) and 69 (SD = 9) years of age, respectively. In primary analyses of cases and controls recruited from the same groups, compared with the lowest quartile of tibia lead, the OR for PD in the highest quartile was 3.21 95% confidence interval (CI), 1.17-8.83. Results were similar but slightly weaker in analyses restricted to cases and controls recruited from the movement disorders clinics only (fourth-quartile OR = 2.57; 95% CI, 1.11-5.93) or when we included controls recruited from sites that did not also contribute cases (fourth-quartile OR = 1.91; 95% CI, 1.01-3.60). We found no association with patella bone lead. Conclusions: These findings, using an objective biological marker of cumulative lead exposure among typical PD patients seen in our movement disorders clinics, strengthen the evidence that cumulative exposure to lead increases the risk of PD.
OBJECTIVETo investigate whether women and men with Parkinson disease (PD) differ in their biochemical and clinical responses to long-term treatment with inosine.
METHODSThe Safety of Urate Elevation ...in Parkinson’s Disease (SURE-PD) trial enrolled 75 people with early PD and baseline serum urate below 6 mg/dL and randomized them to 3 double-blinded treatment armsoral placebo or inosine titrated to produce mild (6.1–7.0 mg/dL) or moderate (7.1–8.0 mg/dL) serum urate elevation for up to 2 years. Parkinsonism, serum urate, and plasma antioxidant capacity were measured at baseline and repeatedly on treatment; CSF urate was assessed once, at 3 months. Here in secondary analyses results are stratified by sex.
RESULTSInosine produced an absolute increase in average serum urate from baseline that was 50% greater in women (3.0 mg/dL) than in men (2.0 mg/dL), consistent with expected lower baseline levels in women. Similarly, only among women was CSF urate significantly greater on mild or moderate inosine (+87% p < 0.001 and +98% p < 0.001, respectively) than on placebo (in contrast to men+10% p = 0.6 and +14% p = 0.4, respectively). Women in the higher inosine dosing group showed a 7.0 Unified Parkinson’s Disease Rating Scale (UPDRS) points/year lower rate of decline vs placebo (p = 0.01). In women, slower rates of UPDRS change were associated with greater increases in serum urate (r = −0.52; p = 0.001), and with greater increases in plasma antioxidant capacity (r = −0.44; p = 0.006). No significant associations were observed in men.
CONCLUSIONSInosine produced greater increases in serum and CSF urate in women compared to men in the SURE-PD trial, consistent with the studyʼs design and with preliminary evidence for slower clinical decline in early PD among women treated with urate-elevating doses of inosine.
CLINICALTRIALS.GOV IDENTIFIERNCT00833690.
CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that inosine produced greater urate elevation in women than men and may slow PD progression in women.
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