In vivo imaging of brain β-amyloid, a hallmark of Alzheimer disease, may assist in the clinical assessment of suspected Alzheimer disease. OBJECTIVE To determine the sensitivity and specificity of positron emission tomography imaging with flutemetamol injection labeled with radioactive fluorine 18 to detect β-amyloid in the brain using neuropathologically determined neuritic plaque levels as the standard of truth. DESIGN, SETTING, AND PARTICIPANTS Open-label multicenter imaging study that took place at dementia clinics, memory centers, and hospice centers in the United States and England from June 22, 2010, to November 23, 2011. Participants included terminally ill patients who were 55 years or older with a life expectancy of less than 1 year. INTERVENTIONS Flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation. MAIN OUTCOMES AND MEASURES Sensitivity and specificity of flutemetamol injection labeled with radioactive fluorine 18 positron emission tomography imaging for brain β-amyloid. Images were reviewed without and with computed tomography scans and classified as positive or negative for β-amyloid by 5 readers who were blind to patient information. In patients who died, neuropathologically determined neuritic plaque levels were used to confirm scan interpretations and determine sensitivity and specificity. RESULTS Of 176 patients with evaluable images, 68 patients (38%) died during the study, were autopsied, and had neuritic plaque levels determined; 25 brains (37%) were β-amyloid negative; and 43 brains (63%) were β-amyloid positive. Imaging was performed a mean of 3.5 months (range, 0 to 13 months) before death. Sensitivity without computed tomography was 81% to 93% (median, 88%). Median specificity was 88%, with 4 of 5 of the readers having specificity greater than 80%. When scans were interpreted with computed tomography images, sensitivity and specificity improved for most readers but the differences were not significant. The area under the receiver operating curve was 0.90. There were no clinically meaningful findings in safety parameters. CONCLUSIONS AND RELEVANCE This study showed that flutemetamol injection labeled with radioactive fluorine 18 was safe and had high sensitivity and specificity in an end-of-life population. In vivo detection of brain β-amyloid plaque density may increase diagnostic accuracy in cognitively impaired patients.

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IntroductionPerformance of the amyloid tracer [18F]flutemetamol was evaluated against three pathology standard of truth (SoT) measures including neuritic plaques (CERAD “original” and “modified” and the amyloid component of the 2012 NIA-AA guidelines).MethodsAfter [18F]flutemetamol imaging, 106 end-of-life patients who died underwent postmortem brain examination for amyloid plaque load. Blinded positron emission tomography scan interpretations by five independent electronically trained readers were compared with pathology measures.ResultsBy SoT, sensitivity and specificity of majority image interpretations were, respectively, 91.9% and 87.5% with “original CERAD,” 90.8% and 90.0% with “modified CERAD,” and 85.7% and 100% with the 2012 NIA-AA criteria.DiscussionThe high accuracy of either CERAD criteria suggests that [18F]flutemetamol predominantly reflects neuritic amyloid plaque density. However, the use of CERAD criteria as the SoT can result in some false-positive results because of the presence of diffuse plaques, which are accounted for when the positron emission tomography read is compared with the 2012 NIA-AA criteria.

Introduction This clinical trial evaluates the efficacy and safety of a 6‐week course of daily neuroAD™ therapy. Methods 131 subjects between 60 and 90 years old, unmedicated for Alzheimer's disease (AD), or on stable doses of an acetylcholinesterase inhibitor and/or memantine, with Mini–Mental State Examination scores between 18 and 26, clinical dementia rating scale scores of 1 or 2, enrolled for a prospective, randomized, double‐blind, sham‐controlled, multicenter clinical trial. Structural brain MRIs were obtained for transcranial magnetic stimulation targeting. Baseline Alzheimer's disease assessment scale—cognitive (ADAS‐Cog) and Clinical Global Impression of Change were assessed. 129 participants were randomized to active treatment plus standard of care (SOC) or sham treatments plus SOC. Results Subjects with baseline ADAS‐Cog ≤ 30 (~85% of study population) showed a statistically significant benefit favoring active over sham. Responder analysis showed 31.7% participants in the active group with ≤ −4 point improvement on ADAS‐Cog versus 15.4% in the sham group. Discussion neuroAD™ Therapy System provides a low‐risk therapeutic benefit for patients with milder AD (baseline ADAS‐Cog ≤30) beyond pharmacologic SOC.

clinicaltrials.gov Identifier: NCT01584440.

Alzheimer’s disease (AD) is the most common cause for dementia worldwide. Until recently, all approved treatments for AD were symptomatic and not disease modifying. On 7 June 2021, the US FDA approved aducanumab, a human IgG1 anti-Aβ monoclonal antibody selective for Aβ aggregates, as the first disease-modifying treatment for AD. Aducanumab is approved in the United States for the treatment of mild cognitive impairment or mild-dementia stage of AD. In this Editorial, we review the trial data for aducanumab in the treatment of AD and the controversies that its approval has generated.

This randomized clinical trial evaluates the safety and efficacy of the monoclonal anti-tau antibody semorinemab in individuals with prodromal to mild Alzheimer disease.

IMPORTANCE Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression. OBJECTIVE To evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD. DESIGN, SETTING, AND PARTICIPANTS In this multicenter cohort study, from November 11, 2009, to January 16, 2014, patients with aMCI underwent positron emission tomography (PET) at baseline followed by local clinical assessments every 6 months for up to 3 years. Patients with aMCI (365 screened; 232 were eligible) were recruited from 28 clinical centers in Europe and the United States. Physicians remained strictly blinded to the results of PET, and the standard of truth was an independent clinical adjudication committee that confirmed or refuted local assessments. Flutemetamol F 18-labeled PET scans were read centrally as either negative or positive by 5 blinded readers with no knowledge of clinical status.