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Amyloid and Tau Accumulation in Young Adults With ADAD
Although the medial temporal lobe is typically the first area of neurofibrillary tangle deposition in aging populations, it is not clear if this is the case for younger individuals who are predisposed to autosomal dominant Alzheimer disease (ADAD). In a cross-sectional study, Quiroz and coauthors used positron emission tomography imaging to measure amyloid and tau deposition in 24 participants (mean [SD] age, 38.0 [7.4] years) from a large Colombian kindred with ADAD. The authors report that amyloid accumulates in the cortex of unimpaired presenilin 1 E280A mutation carriers 10 to 15 years before symptom onset, whereas tau deposits emerge in the medial temporal lobe approximately 6 years before and then spread into the cortex as carriers move closer to clinical onset. These findings suggest that amyloid prompts the spread of tau pathology beyond the medial temporal lobe and that the presence of tau is closely associated with memory decline. Editorial perspective is provided by McDade and Bateman.
Risk of Serotonin Syndrome With Triptans and Antidepressants
In 2006, the US Food and Drug Administration issued a warning regarding the potential risk of serotonin syndrome with coprescription of triptan antimigraine drugs and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants based on a small number of case reports. In this population-based study using data from the Partners Research Data Registry, Orlova and coauthors identified 47 968 patients who had been prescribed triptans and 19 017 patients who had been prescribed antidepressants between January 2001 and December 2014. A total of 17 patients had possible serotonin syndrome, and only 2 patients received a confirmed diagnosis of serotonin syndrome. Affective disorder can likely be treated safely in the patients who also need triptans to treat migraine and who are at a low risk for serotonin syndrome. This study also demonstrates that the frequency of concomitant use of these medications remained stable over the study period, illustrating a clear need to treat both conditions.
Continuing Medical Education
Developing a Myotonic Dystrophy Type 1 Prognosis Score
Life expectancy is greatly shortened in patients with myotonic dystrophy type 1, but there is no reliable prognostic risk score to predict survival. In this longitudinal cohort study from January 2000 to November 2014, Wahbi and coauthors studied 1296 adults (mean [SD] age, 39.8 [13.7] years) with myotonic dystrophy type 1 and developed and validated a practical risk score that predicts 10-year survival based on a set of common patient characteristics, including age, diabetes, need for support when walking, heart rate, systolic blood pressure, first-degree atrioventricular block, bundle-branch block, and lung vital capacity. The score may prove useful for patients living with myotonic dystrophy type 1 and physicians.
Circadian Rest-Activity Pattern Changes and Preclinical AD
Disturbances of circadian rhythm are associated with both aging and neurodegenerative diseases, but it is not clear if circadian changes are present in the presymptomatic phase of Alzheimer disease (AD). In this cross-sectional study, Musiek and coauthors assessed circadian rest-activity patterns in 189 cognitively normal individuals (mean [SD] age, 66.6 [8.3] years) relative to AD biomarkers. Preclinical AD was associated with fragmentation of circadian rest-activity patterns, even after correction for age and sex. These findings indicate that circadian disturbance occurs very early in AD, prior to any cognitive symptoms.
Highlights. JAMA Neurol. 2018;75(5):525. doi:10.1001/jamaneurol.2017.2636
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