Advances in neuroimaging in frontotemporal dementia

Frontotemporal dementia (FTD) is a clinically and neuroanatomically heterogeneous neurodegenerative disorder with multiple underlying genetic and pathological causes. Whilst initial neuroimaging studies highlighted the presence of frontal and temporal lobe atrophy or hypometabolism as the unifying feature in patients with FTD, more detailed studies have revealed diverse patterns across individuals, with variable frontal or temporal predominance, differing degrees of asymmetry, and the involvement of other cortical areas including the insula and cingulate, as well as subcortical structures such as the basal ganglia and thalamus. Recent advances in novel imaging modalities including diffusion tensor imaging, resting-state functional magnetic resonance imaging and molecular positron emission tomography imaging allow the possibility of investigating alterations in structural and functional connectivity and the visualisation of pathological protein deposition. This review will cover the major imaging modalities currently used in research and clinical practice, focusing on the key insights they have provided into FTD, including the onset and evolution of pathological changes and also importantly their utility as biomarkers for disease detection and staging, differential diagnosis and measurement of disease progression. Validating neuroimaging biomarkers that are able to accomplish these tasks will be crucial for the ultimate goal of powering upcoming clinical trials by correctly stratifying patient enrolment and providing sensitive markers for evaluating the effects and efficacy of disease-modifying therapies

Molecular nexopathies: a new paradigm of neurodegenerative disease.

Neural networks provide candidate substrates for the spread of proteinopathies causing neurodegeneration, and emerging data suggest that macroscopic signatures of network disintegration differentiate diseases. However, how do protein abnormalities produce network signatures? The answer may lie with 'molecular nexopathies': specific, coherent conjunctions of pathogenic protein and intrinsic network characteristics that define network signatures of neurodegenerative pathologies. Key features of the paradigm that we propose here include differential intrinsic network vulnerability to propagating protein abnormalities, in part reflecting developmental structural and functional factors; differential vulnerability of neural connection types (e.g., clustered versus distributed connections) to particular pathogenic proteins; and differential impact of molecular effects (e.g., toxic-gain-of-function versus loss-of-function) on gradients of network damage. The paradigm has implications for understanding and predicting neurodegenerative disease biology

Engaging Patients in Health System Transformation: The experience of the Maine Health Access Foundation\u27s (MeHAF) Advancing Payment Reform Initiative

In 2001, the Institute of Medicine (IOM) identified patient centeredness as one of six essential aims of “a new health care system for the 21st century”.1 Since that time, we have begun a gradual shift from a professionally driven system toward one that is more “patient centered” or “consumer centered,” recognizing and incorporating patients’ perspectives in decisions in clinical care, delivery system, and policies. As the health care system responds to new payment approaches and positions itself to achieve the Triple Aim (i.e. better care, lower cost, enhanced patient experience), it is important to assess how organizations that are moving to advance health care service delivery and payment reform are integrating patient engagement into the health system transformation process. Since 2011, the Maine Health Access Foundation’s Advancing Payment Reform initiative has funded 13 health system transformation projects. Diverse in their approach, each has undertaken efforts to achieve greater patient engagement ranging from involving patients and families as informed and active participants in their own health care (e.g. shared decision making, self-management) to involving patients at the organizational or policy-level through consumer advisory boards and other means to provide guidance for health system transformation. This brief summarizes the experience of these grantees in developing and implementing strategies to engage patients in payment reform and delivery system redesign.2 The purpose is to identify common themes and lessons within and across these initiatives to inform future patient engagement efforts

Novel associations of bile acid diarrhoea with fatty liver disease and gallstones: a cohort retrospective analysis.

Background Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods A cohort of patients with chronic diarrhoea who underwent 75selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively. Additional clinical details available from the electronic patient record, including imaging, colonoscopy, chemistry and histopathology reports were used to calculate the prevalence of fatty liver disease, gallstones, colonic neoplasia and microscopic colitis, which was compared for BAD, the primary BAD subset and control patients with diarrhoea. Findings Of 578 patients, 303 (52%) had BAD, defined as a SeHCAT 7d retention value 31 ng/mL with imaging showing fatty liver (p40 IU/L. In 176 subjects with gallbladder imaging, 27% had gallstones, 7% had a prior cholecystectomy and 34% either of these. The median SeHCAT values were lower in those with gallstones (3.8%, p<0.0001), or gallstones/cholecystectomy (7.2%, p<0.001), compared with normal gallbladder imaging (14%). Overall, BAD had an OR of 2.0 for gallstones/cholecystectomy (p<0.05). BAD was not significantly associated with colonic adenoma/carcinoma or with microscopic colitis. Interpretation The diagnosis of BAD is associated with fatty liver disease and with gallstones. The reasons for these associations require further investigation into potential metabolic causes

The Role of Organizational Change in Health System and Payment Reform

The Maine Health Access Foundation (MeHAF) has awarded grants to 14 Maine health organizations to date to mitigate the increasing cost of health care in Maine through innovative delivery system and payment reform strategies that preserve access, improve quality, and offer better value. As part of the evaluation of this initiative, the University of Southern Maine Muskie School of Public Service (Muskie School) is producing a series of issue briefs that capture common themes and challenges across grantees in achieving payment reform and health system delivery change to assess lessons learned. This is the first issue brief which describes our evaluation approach and presents an analysis of the role of organizational change among grantees engaged in delivery system and payment reform

A novel A781V mutation in the CSF1R gene causes hereditary diffuse leucoencephalopathy with axonal spheroids

We report a family with a novel CSF1R mutation causing hereditary diffuse leucoencephalopathy with axonal spheroids. Family members presented with neuropsychiatric and behavioural symptoms, with subsequent development of motor symptoms and gait disturbance. MRI brain showed extensive white matter change with a frontal predominance and associated atrophy in two members of the family. Genetic testing revealed a novel mutation c.2342C>T (p.A781V) in the CSF1R gene in two brothers of the family. This report highlights the difficulties in diagnosing HDLS and discusses the indications for testing for mutations in the CSF1R gene

Health Data and Financing and Delivery System Reform: Is the Glass Half Full or Half Empty?

In 2011, the Maine Health Access Foundation (MeHAF) launched its Advancing Payment Reform initiative to stimulate innovative payment and delivery system reform strategies in Maine. This policy paper reports on the health data experience of the 14 program grantees, using interviews conducted in 2013-14 and other information garnered from the evaluation of the initiative. The paper focuses on the role and impact of health data in supporting implementation and monitoring of specific components of the projects’ reform strategies; the data infrastructure challenges the projects have faced and how those have been addressed; and the generalizable lessons learned so far for improving data usefulness, access, analysis, and integration to support payment and delivery system reform. Support for this policy paper was provided by the Maine Health Access Foundation