9 research outputs found
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Dementia assessment and management in primary care settings: a survey of current provider practices in the United States.
BACKGROUND:Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management. METHODS:A cross-sectional survey with 150 PCPs and 50 neurologists in the United States who evaluated more than 10 patients over age 55 per month. The 51-item survey assessed clinical practice characteristics, and confidence, perceived barriers, and typical practices when diagnosing and managing patients with NCDs. RESULTS:PCPs and neurologists reported similar confidence and approaches to general medical care and laboratory testing. Though over half of PCPs performed cognitive screening or referred patients for cognitive testing in over 50% of their patients, only 20% reported high confidence in interpreting results of cognitive tests. PCPs were more likely to order CT scans than MRIs, and only 14% of PCPs reported high confidence interpreting brain imaging findings, compared to 70% of specialists. Only 21% of PCPs were highly confident that they correctly recognized when a patient had an NCD, and only 13% were highly confident in making a specific NCD diagnosis (compared to 72 and 44% for neurologists, both p < 0.001). A quarter of all providers identified lack of familiarity with diagnostic criteria for NCD syndromes as a barrier to clinical practice. CONCLUSIONS:This study demonstrates how PCPs approach diagnosis and management of patients with NCDs, and identified areas for improvement in regards to cognitive testing and neuroimaging. This study also identified all providers' lack of familiarity with published diagnostic criteria for NCD syndromes. These findings may inform the development of new policies and interventions to help providers improve the efficacy of their decision processes and deliver better quality care to patients with NCDs
The Brain Health Assessment for Detecting and Diagnosing Neurocognitive Disorders
Background/objectivesBrief cognitive screens lack the sensitivity to detect mild cognitive impairment (MCI) or support differential diagnoses. The objective of this study was to validate the 10-minute, tablet-based University of California, San Francisco (UCSF) Brain Health Assessment (BHA) to overcome these limitations.DesignCross-sectional.SettingUCSF Memory and Aging Center.ParticipantsOlder adults (N = 347) (neurologically healthy controls (n = 185), and individuals diagnosed with MCI (n = 99), dementia (n = 42), and as normal with concerns (n = 21)).MeasurementsThe BHA includes subtests of memory, executive function and speed, visuospatial skills, and language and an optional informant survey. Participants completed the Montreal Cognitive Assessment (MoCA) and criterion-standard neuropsychological tests. Standardized structural 3T brain magnetic resonance imaging was performed in 145 participants.ResultsAt a fixed 85% specificity rate, the BHA had 100% sensitivity to dementia and 84% to MCI; the MoCA had 75% sensitivity to dementia and 25% to MCI. The BHA had 83% sensitivity to MCI likely due to AD and 88% to MCI unlikely due to AD, and the MoCA had 58% sensitivity to MCI likely AD and 24% to MCI unlikely AD. The BHA subtests demonstrated moderate to high correlations with the criterion-standard tests from their respective cognitive domains. Memory test performance correlated with medial temporal lobe volumes; executive and speed with frontal, parietal, and basal ganglia volumes; and visuospatial with right parietal volumes.ConclusionThe BHA had excellent combined sensitivity and specificity to detect dementia and MCI, including MCI due to diverse etiologies. The subtests provide efficient, valid measures of neurocognition that are critical in making a differential diagnosis
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Protein network analysis reveals selectively vulnerable regions and biological processes in FTD.
ObjectiveThe neuroanatomical profile of behavioral variant frontotemporal dementia (bvFTD) suggests a common biological etiology of disease despite disparate pathologic causes; we investigated the genetic underpinnings of this selective regional vulnerability to identify new risk factors for bvFTD.MethodsWe used recently developed analytical techniques designed to address the limitations of genome-wide association studies to generate a protein interaction network of 63 bvFTD risk genes. We characterized this network using gene expression data from healthy and diseased human brain tissue, evaluating regional network expression patterns across the lifespan as well as the cell types and biological processes most affected in bvFTD.ResultsWe found that bvFTD network genes show enriched expression across the human lifespan in vulnerable neuronal populations, are implicated in cell signaling, cell cycle, immune function, and development, and are differentially expressed in pathologically confirmed frontotemporal lobar degeneration cases. Five of the genes highlighted by our differential expression analyses, BAIAP2, ERBB3, POU2F2, SMARCA2, and CDC37, appear to be novel bvFTD risk loci.ConclusionsOur findings suggest that the cumulative burden of common genetic variation in an interacting protein network expressed in specific brain regions across the lifespan may influence susceptibility to bvFTD
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Frequency of frontotemporal dementia gene variants in C9ORF72, MAPT, and GRN in academic versus commercial laboratory cohorts.
BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia, and elucidating its genetic underpinnings is critical. FTLD research centers typically recruit patient cohorts that are limited by the center's specialty and the ways in which its geographic location affects the ethnic makeup of research participants. Novel sources of data are needed to get population estimates of the contribution of variants in known FTLD-associated genes.MethodsWe compared FLTD-associated genetic variants in microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome nine open reading frame 72 (C9ORF72) from an academic research cohort and a commercial clinical genetics laboratory. Pathogenicity was assessed using guidelines of the American College of Medical Genetics and Genomics and a rule-based DNA variant assessment system. We conducted chart reviews on patients with novel or rare disease-associated variants.ResultsA total of 387 cases with FTLD-associated variants from the commercial (n=2,082) and 78 cases from the academic cohort (n=2,089) were included for analysis. In the academic cohort, the most frequent pathogenic variants were C9ORF72 expansions (63%, n=49), followed by GRN (26%, n=20) and MAPT (11%, n=9). Each gene's contribution to disease was similarly ranked in the commercial laboratory but differed in magnitude: C9ORF72 (89%, n=345), GRN (6%, n=24), and MAPT (5%, n=19). Of the 37 unique GRN/MAPT variants identified, only six were found in both cohorts. Clinicopathological data from patients in the academic cohort strengthened classification of two novel GRN variant as pathogenic (p.Pro166Leufs*2, p.Gln406*) and one GRN variant of unknown significance as a possible rare risk variant (p.Cys139Arg).ConclusionDifferences in gene frequencies and identification of unique pathogenic alleles in each cohort demonstrate the importance of data sharing between academia and community laboratories. Using shared data sources with well-characterized clinical phenotypes for individual variants can enhance interpretation of variant pathogenicity and inform clinical management of at-risk patients and families
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia.
The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA's relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration