Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Nov 2021
Subjective cognitive complaints at age 70: associations with amyloid and mental health.
To investigate subjective cognitive decline (SCD) in relation to β-amyloid pathology and to test for associations with anxiety, depression, objective cognition and family history of dementia in the Insight 46 study. ⋯ This cross-sectional study demonstrates that symptoms of SCD are associated with both β-amyloid pathology, and more consistently, trait anxiety in a population-based cohort of older adults, at an age when those who are destined to develop dementia are still likely to be some years away from symptoms. This highlights the necessity of considering anxiety symptoms when assessing Alzheimer's disease pathology and SCD.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2021
Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases.
We used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres. ⋯ Integrating deep phenotyping, gene filter algorithms and biological assays increased diagnostic yield of exome sequencing, identified novel pathogenic variants and extended phenotypes of difficult to diagnose rare neurogenetic disorders in an outpatient clinic setting.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2021
ReviewBlood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer's disease: a focused review on recent advances.
Discovery and development of clinically useful biomarkers for Alzheimer's disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-β (Aβ) peptides and phosphorylated tau (P-tau). ⋯ In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish Aβ and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of Aβ peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2021
ReviewIschaemic stroke in anticoagulated patients with atrial fibrillation.
Anticoagulation substantially reduces the risk of stroke in patients with atrial fibrillation (AF). However, recent studies have shown that up to 22%-36% of patients on anticoagulation will suffer an ischaemic stroke (IS). In this narrative review, we provide an overview of risk factors, mechanisms, management of acute IS and strategies for secondary prevention for patients with AF with stroke despite oral anticoagulation. ⋯ The identification of one or more possible mechanisms of stroke despite anticoagulation may allow for a more targeted and individualised approach for secondary prevention. There are limited data to guide management in such patients, and strategies to prevent recurrent strokes include strict risk factor control and therapies targeting the most likely stroke mechanism. In cases where AF is suspected to be the culprit, clinical trials are needed to test the safety and efficacy of left atrial appendage occlusion plus anticoagulation versus continued anticoagulation alone.