Clinical Deep Phenotyping of ABCA7 Mutation Carriers

Background and ObjectivesPutative loss-of-function (pLOF) ABCA7 variants that increase Alzheimer disease (AD) risk were identified; however, deep phenotypic characterization of these variants in mutation carriers is limited. We aimed to obtain deep clinical phenotypes of ABCA7 pLOF mutation carriers from a large retrospectively reviewed series.MethodsGenotypes were determined for 5,353 individuals evaluated at Mayo Clinic for 6 reported ABCA7 pLOF variants (p.E709fs, p.Trp1214X, p.L1403fs, c.4416+2T>G, p.E1679X, and c.5570+5G>C). Medical records of 100 mutation carriers were reviewed for demographics, clinical phenotypes, and diagnoses. Eleven mutation carriers had autopsy-based neuropathologic diagnoses.ResultsWe confirmed that ABCA7 pLOF mutations confer AD risk in our series of 2,495 participants with AD and 2,858 cognitively unaffected participants. Clinical review of 100 mutation carriers demonstrated phenotypic variability of clinical presentations with both memory and nonmemory cognitive impairment and a subset presenting with motor symptoms. There was a wide range of age at onset of cognitive symptoms (ages 56–92 years, mean = 75.6). Ten of the 11 autopsied mutation carriers had AD neuropathology. ABCA7 pLOF mutation carriers had higher rates of depression (41.6%) and first-degree relatives with cognitive impairment (38.1%) compared with the general population.DiscussionOur study provides a deep clinical review of phenotypic characteristics of mutation carriers for 6 ABCA7 pLOF mutations. Although memory impairment was the most common initial symptom, nonmemory cognitive and/or motor symptoms were present in a substantial number of mutation carriers, highlighting the heterogeneity of clinical features associated with these mutations. Likewise, although AD neuropathology is the most common, it is not the only autopsy-based diagnosis. Presence of earlier ages at onset, higher rates of depression, and first-degree relatives with cognitive impairment among mutation carriers suggest that these genetic variants may have more aggressive clinical features than AD in the general population. This deep phenotyping study of ABCA7 pLOF mutation carriers provides essential genotype-phenotype correlations for future precision medicine approaches in the clinical setting.

Pain management in the emergency department: a clinical review

Pain is one of the most common reasons for patients to visit the emergency department. The ever-growing research on emergency department analgesia has challenged the current practices with respect to the optimal analgesic regimen for acute musculoskeletal pain, safe and judicious opioid prescribing, appropriate utilization of non-opioid therapeutics, and non-pharmacological treatment modalities. This clinical review is set to provide evidence-based answers to these challenging questions.

Drug information of Aducanumab and its effectiveness for Alzheimer’s disease: A clinical review

Alzheimer’s disease (AD) is the main cause of disability in people older than 60 years. More than 1 million cases per year reported in India. AD and other kinds of dementia are more common as individuals become older, affecting 1 in every 14 people over the age of 65 and 1 in every 6 people over the age of 80. ADUHELM (Aducanumab) is a monoclonal antibody, new class of medication needed for treatment of AD. The latest drug used to treat underlying cause of AD and recent studies shown to be efficacious and safe for the AD. Our review emphasizes on the drug information of Aducanumab and its clinical importance in AD.