Neuroimaging in Dementia

Dementia is a common illness with an incidence that is rising as the aged population increases. There are a number of neurodegenerative diseases that cause dementia, including Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal dementia, which is subdivided into the behavioral variant, the semantic variant, and nonfluent variant. Numerous other neurodegenerative illnesses have an associated dementia, including corticobasal degeneration, Creutzfeldt–Jakob disease, Huntington’s disease, progressive supranuclear palsy, multiple system atrophy, Parkinson’s disease dementia, and amyotrophic lateral sclerosis. Vascular dementia and AIDS dementia are secondary dementias. Diagnostic criteria have relied on a constellation of symptoms, but the definite diagnosis remains a pathologic one. As treatments become available and target specific molecular abnormalities, differentiating amongst the various primary dementias early on becomes essential. The role of imaging in dementia has traditionally been directed at ruling out treatable and reversible etiologies and not to use imaging to better understand the pathophysiology of the different dementias. Different brain imaging techniques allow the examination of the structure, biochemistry, metabolic state, and functional capacity of the brain. All of the major neurodegenerative disorders have relatively specific imaging findings that can be identified. New imaging techniques carry the hope of revolutionizing the diagnosis of neurodegenerative disease so as to obtain a complete molecular, structural, and metabolic characterization, which could be used to improve diagnosis and to stage each patient and follow disease progression and response to treatment. Structural and functional imaging modalities contribute to the diagnosis and understanding of the different dementias

Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications

In the past decade, positron emission tomography (PET) with carbon-11-labeled Pittsburgh Compound B (PIB) has revolutionized the neuroimaging of aging and dementia by enabling in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer's disease (AD). Studies suggest that PIB-PET is sensitive for AD pathology, can distinguish AD from non-AD dementia (for example, frontotemporal lobar degeneration), and can help determine whether mild cognitive impairment is due to AD. Although the short half-life of the carbon-11 radiolabel has thus far limited the use of PIB to research, a second generation of tracers labeled with fluorine-18 has made it possible for amyloid PET to enter the clinical era. In the present review, we summarize the literature on amyloid imaging in a range of neurodegenerative conditions. We focus on potential clinical applications of amyloid PET and its role in the differential diagnosis of dementia. We suggest that amyloid imaging will be particularly useful in the evaluation of mildly affected, clinically atypical or early age-at-onset patients, and illustrate this with case vignettes from our practice. We emphasize that amyloid imaging should supplement (not replace) a detailed clinical evaluation. We caution against screening asymptomatic individuals, and discuss the limited positive predictive value in older populations. Finally, we review limitations and unresolved questions related to this exciting new technique

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS