Early Amyloid PET Leads to High Diagnostic Confidence for Patients With CI

Early amyloid PET in patients with memory issues, compared with those who underwent PET later, led to a diagnosis with very high confidence at 3 months.

Early amyloid positron emission tomography (PET) in patients with cognitive impairment strengthens diagnostic confidence and reduces diagnostic workup time, according to study findings published in JAMA Neurology

Amyloid PET is a tool that directly allows the visualization of amyloid deposition, a hallmark of Alzheimer disease (AD). Despite its use, evidence on its clinical utility and cost-effectiveness is limited. As such, researchers aimed to investigate whether patients who received amyloid PET in early diagnostic workup were able to obtain an etiological diagnosis with a high diagnostic confidence, compared with those who have not undergone testing.

In the Amyloid Imaging to Prevent Alzheimer’s Disease Diagnostic and Patient Management Study (AMYPAD-DPMS; ClinicalTrialsRegister.eu EudraCT Number: 2017-002527-21), a prospective, multicenter, randomized controlled trial, the researchers assessed the clinical effects of amyloid PET in patients from a memory clinic from April 16, 2018 to October 30, 2020. Participants were enrolled from 8 European academic memory clinics and subdivided into 3 study groups.

Arm 1: Amyloid PET was performed within 1-month of diagnostic workup.

Arm 2: Patients had late amyloid PET (after 2 months from baseline) in diagnostic workup.

Arm 3: Amyloid PET was performed upon the physician’s request (free choice arm).

All participants had clinical variables, such as cognitive stage, etiological diagnosis and diagnostic confidence, and treatment plan obtained during clinical visits (up to 5 clinical visits; baseline and after 3, 6, 13, and 18 months).

[W]idespread implementation of this imaging technique may improve the timely diagnostic workup of patients under evaluation for cognitive decline.

Inclusion criteria consisted of patients with a cognitive concern that the managing physician considered was possibly due to AD, as well as undergoing diagnostic workup, including magnetic resonance imaging (MRI) and/or computed tomography (CT). Individuals with prior PET and/or AD biomarker workup were excluded from the study.

Primary outcome was proportion of participants who received an etiological diagnosis with a high diagnostic confidence (>90%) after 3 months in arm 1 vs arm 2. Secondary outcomes included changes in etiological diagnosis, diagnostic confidence, or treatment plan.

Of 840 enrolled patients, 794 were included in the final analysis, that of which 736 underwent amyloid PET during the course of the study. Amyloid positivity was found in 369 of 736 cases (50%). The prevalence of amyloid positivity was associated with an increased severity of cognitive stage:

  • 67 of 222 participants (30%) with subjective cognitive decline (SCD),
  • 146 of 297 (49%) with mild cognitive decline (MCI), and
  • 156 of 217 (72%) with dementia (P <.001).

A higher proportion of participants with a high diagnostic confidence (≥90%) after 3 months was found in those in arm 1 (mean age, 71 years; 55% men; 109/272, 40%; 95% CI, 34%-46%; P < .001) compared with arm 2 (mean age, 71 years; 52% men; 30/260, 11%; 95% CI, 8%-16%). Diagnostic confidence was found to be higher in arm 1 across the entire spectrum of cognitive decline (SCD vs MCI vs dementia).

Arm 1 had a higher proportion of participants changing etiological diagnosis (112/253, 44%) than in arm 3 (77/262, 29%; P = .002) and arm 2 (28/259, 11%; P < .001). In arm 1 and arm 3, changes in etiological diagnosis were found to be more consistent than inconsistent with accompanying amyloid PET result (arm 1: 107/112, 96% vs 5/112, 4%; P < .001; arm 3: 63/68, 93% vs 5/68, 7%; P <.001).

Diagnostic confidence increased more in participants with a diagnosis of AD after 3 months in arm 1 and arm 3 compared with arm 2 (+14%, from 71% to 85%; P < .001; +11%, from 73% to 84%; P <.001; +1%, from 73% to 74%, respectively).

No statistically significant changes in cognition-specific medications after 3 months were found in any of the 3 arms, although cognition-specific medications occurred more frequently in arm 1 and arm 3 after a positive, rather than a negative amyloid PET (arm 1: 31/37, 84% vs 6/37, 16%; P <.001; arm 3: 24/27, 89% vs 3/27, 11%; P <.001).

Limitations include the lack of health-related outcomes (improving quality of life, preventing death and disability), as these outcomes require long term follow up. Additionally, generalizability is limited as the sample population was taken from academic memory clinic populations.

The researchers concluded that “This evidence from AMYPAD-DPMS of the clinical effect of amyloid PET in a European memory clinic population suggests that widespread implementation of this imaging technique may improve the timely diagnostic workup of patients under evaluation for cognitive decline.”

Disclosures: Several study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.


Altomare D, Barkhof F, Caprioglio C, et al. Clinical effect of early vs late amyloid positron emission tomography in memory clinic patients: the AMYPAD-DPMS randomized clinical trial. JAMA Neurol. Published online May 8, 2023. doi:10.1001/jamaneurol.2023.0997