Citations

ObjectiveWhite matter hyperintensities (WMHs) are areas of increased signal on T2‐weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD.MethodsThe study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first‐degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed‐effects piece‐wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO.ResultsMutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset.InterpretationAutosomal‐dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929–939

SummaryBackgroundThyroid ultrasound to assess for nodular growth is commonly performed during the follow‐up of patients with benign thyroid nodules, with the goal of identifying patients with a missed diagnosis of thyroid cancer. The objective of this study was to summarize the evidence regarding the diagnostic accuracy of growth during follow‐up of benign thyroid nodules for thyroid cancer.MethodsWe searched multiple electronic databases using a search strategy designed by an experienced medical librarian from inception to March 2015. Eligible studies included patients with benign thyroid nodules assessed for growth during follow‐up and evaluated for thyroid cancer either by surgical histology or a repeat fine needle aspiration biopsy. Reviewers working independently and in duplicate recorded data and assessed each study.ResultsThe seven eligible studies lacked safeguards against bias and generated results that were imprecise with wide confidence intervals and inconsistent across studies. This warrants very low confidence in these results. The odds of nodule growth in patients with thyroid cancer on histopathology over these odds in patients without thyroid cancer (diagnostic odds ratio) was 0·58 (95% CI: 0·26–1·3); the diagnostic odds ratio was 2·2 (95% CI: 0·26–18) when an abnormal repeat biopsy was the reference standard.ConclusionThe body of evidence linking nodule growth with thyroid cancer during the follow‐up of benign nodules warrants very low confidence. In the era of high‐value health care, the commonplace practice of following benign thyroid nodules with serial ultrasound assessment of growth to diagnose cancer can be questioned, calling for imminent evaluation.