Lancet neurology
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Hereditary transthyretin (TTR) amyloid polyneuropathy is an autosomal dominant life-threatening disorder. TTR is produced mainly by the liver but also by the choroid plexus and retinal pigment epithelium. Detailed clinical characterisation, identification of clinical red flags for misdiagnosis, and use of biomarkers enable early diagnosis and treatment. ⋯ As none of the disease-modifying therapies can cross the blood-brain barrier, TTR deposition in the CNS, which can cause stroke and cognitive impairment, remains an important unaddressed issue. CRISPR-Cas9-based one-time TTR editing therapy is being investigated in a phase 1 clinical study. Identification of the earliest stages of pathogenesis in TTR variant carriers is a major challenge that needs addressing for optimal management.
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Neurodegenerative disorders, including Alzheimer's disease, are associated with microgliosis. Microglia have long been considered to have detrimental roles in Alzheimer's disease. However, functional analyses of genes encoding risk factors that are linked to late-onset Alzheimer's disease, and that are enriched or exclusively expressed in microglia, have revealed unexpected protective functions. ⋯ Several anti-TREM2 antibodies are in early clinical trials, and current efforts aim to achieve more efficient transport of these antibodies across the blood-brain barrier. PET imaging could be used to monitor target engagement. Data from animal models, and biomarker studies in patients, further support a rationale for boosting TREM2 functions during the preclinical stage of Alzheimer's disease.
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Review
Long-term risk of cardiovascular disease after traumatic brain injury: screening and prevention.
Traumatic brain injury (TBI) is highly prevalent among individuals participating in contact sports, military personnel, and in the general population. Although it is well known that brain injury can cause neurological and psychiatric complications, evidence from studies on individuals exposed to a single or repetitive brain injuries suggests an understudied association between TBI and the risk of developing chronic cardiovascular diseases and risk factors for cardiovascular disease. ⋯ Similar observations made in military and professional American-style football cohorts suggest causal pathways through which modifiable cardiovascular risk factors might mediate the relationship between brain injury and chronic neurological diseases. A better understanding of cardiovascular disease risk after TBI combined with a proactive, targeted screening programme might mitigate long-term morbidity and mortality in individuals with TBI, and improve their quality of life.
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Migraine is an evolving, and sometimes lifelong disorder. The prevalence of episodic migraine peaks among individuals aged in their late 30s, implying a tendency for the disorder to remit with increasing age thereafter, whereas chronic migraine is more likely to persist into later life. Diagnosis and treatment of migraine in older adults, defined as individuals aged 60 years or older, is rendered more complex by increasing probabilities of atypical clinical features and comorbidities, with patients' comorbidities sometimes limiting their therapeutic options. ⋯ Long-term longitudinal studies of individuals with migraine would be particularly informative, with the potential not only to suggest new research directions, but also to lead to the identification of novel therapeutic agents. Although several novel migraine medications are becoming available, their effectiveness, tolerability, and safety often remain uncertain in older adults, who have commonly been excluded from the evaluation of these agents in randomised controlled trials, or who constitute only a small proportion of study populations. There is a need to recognise these limitations in the available evidence, and the specific, and often unmet, clinical needs of older adults with migraine, not least because older adults constitute an increasing proportion of populations worldwide.
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About 300 million adults undergo non-cardiac surgery annually. Although, in this setting, the incidence of perioperative stroke is low, the absolute number of patients experiencing a stroke is substantial. Furthermore, most patients with this complication will die or end up with severe disability. ⋯ Evidence shows that traditional stroke risk factors including older age, hypertension, and atrial fibrillation are also associated with perioperative stroke; previous stroke is the strongest risk factor for perioperative stroke. Increasing evidence also suggests the pathogenic role of perioperative events, such as hypotension, new atrial fibrillation, paradoxical embolism, and bleeding. Clinicians involved in perioperative care should be aware of this evidence on prevention strategies to improve patient outcomes after non-cardiac surgery.