Discussion
MCI
DISEASE PROGRESSION, SECONDARY, NEURODEGENERATION
In this randomized clinical trial, we demonstrated that performing amyloid PET early in the diagnostic workup allowed 40% of memory clinic patients to receive an etiological diagnosis with very high confidence after only 3 months, 3.5 times more frequently than patients who had not yet undergone amyloid PET (11%). The major clinical impact of an early amyloid PET has been further confirmed by secondary analyses on changes in etiological diagnosis and diagnostic confidence. Interestingly, a significant clinical effect of amyloid PET was consistently observed across the 3 cognitive stages, suggesting that amyloid PET is clinically useful not only in MCI (ie, the population considered to benefit the most from biomarker assessmentA timely high-confidence diagnosis is critical to the efficacy of disease-modifying therapies, especially anti-amyloid drugs, whose efficacy might decrease with advancing disease progression. With the advent of disease-modifying therapies, amyloid PET might be used as a mere gateway to treatment, with the consequence that diagnostic outcomes will be no longer relevant. However, it has been estimated that the proportion of the real-world memory clinic population for whom aducanumab will be indicated (if the label mirrors eligibility criteria of phase 3 clinical trials) ranges between 1% and 12%,Consistent with the IDEAS study,One of the unique features of AMYPAD-DPMS is the assessment of the clinical impact of amyloid PET in individuals with SCD+ in a randomized controlled fashion. We observed that 30% of arm 1 participants with SCD+ were amyloid positive. This prevalence is slightly higher than a recent estimate of amyloid positivity in individuals with SCD of similar age (27%).It is worth noting that cerebrospinal fluid analysis might provide information similar to that provided by amyloid PET at a remarkably lower cost and can provide additional information on other biomarkers (eg, phosphorylated tau or neurofilament light). Nevertheless, amyloid PET is less invasive and better accepted by patients (indeed, in arm 3, 11% of participants explicitly wanted to undergo an amyloid PET, and 5% underwent amyloid PET because they refused lumbar puncture), and it is the biomarker of choice when lumbar puncture is contraindicated. Moreover, recent evidence shows that a dual-phase acquisition of amyloid PET imaging can also offer information on cortical perfusion (a proxy of metabolism and thus a measure of neurodegeneration) when additional early-phase images are acquired after tracer injection.