COMMENTARY

Amyloid PET May Aid Clinical Diagnosis of Dementia, Whether Negative or Positive

Laurie L. Barclay, MD

Disclosures

August 30, 2018

Association of Amyloid Positron Emission Tomography With Changes in Diagnosis and Patient Treatment in an Unselected Memory Clinic Cohort: The ABIDE Project

de Wilde A, van der Flier WM, Pelkmans W, et al
JAMA Neurol. 2018 Jun 11. [Epub ahead of print]

Summary

Although previous research has assessed the diagnostic impact of amyloid positron emission tomography (PET) in various research samples, these populations may not be representative of daily practice. Clinical implementation of amyloid PET imaging based on these earlier studies is therefore problematic. The goal of the present study was to determine the association of amyloid PET findings with changes in diagnosis, diagnostic confidence, treatment, and patient experiences in an unselected memory clinic cohort.

As part of their routine diagnostic dementia workup, 866 patients seen between January 2015 and December 2016 at the VU University Medical Center (Amsterdam, Netherlands) tertiary memory clinic were offered amyloid PET scanning using fluoride-18 florbetaben. Of these patients, 358 (41%) declined to participate and 32 (4%) were excluded. To enrich the remaining sample of 476 patients, the investigators also included 31 patients with mild cognitive impairment from the University Medical Center Utrecht (Utrecht, Netherlands) memory clinic. Mean age was 65 ± 8 years, 39% of participants were women, and mean Mini-Mental State Examination score was 25 ± 4.

Neurologists determined a diagnosis before and after amyloid PET scanning for each patient. Diagnoses including a clinical syndrome such as dementia, mild cognitive impairment, or subjective cognitive decline, and a suspected etiology such as Alzheimer disease (AD) or non-AD, with a confidence level ranging from 0% to 100%. Neurologists also decided on adjunctive testing, pharmacotherapy, and other treatments for each patient. Patients underwent clinical follow-up 1 year after PET scanning. The main study endpoints were post-PET changes in diagnosis, diagnostic confidence, and patient treatment.

Diagnoses were AD dementia (32% of patients), non-AD dementia (14%), mild cognitive impairment (23%), and subjective cognitive decline (31%). Nearly half (48%) of patients had positive amyloid PET findings. After amyloid PET scanning, the suspected etiology changed for 25% of patients, more often because of a negative (31%) than a positive finding (18%; P < .01).

Patients older than the typical age at AD onset of 65 years more frequently had diagnostic changes in suspected etiology after PET scanning compared with younger patients (29% vs 20%, respectively; P < .05). Mean diagnostic confidence increased from 80% to 89% after scanning (P < .001). For nearly one quarter of patients (24%), management was changed after PET scanning, mostly because of additional workup and treatment. Disclosing the amyloid PET findings to patients reduced their uncertainty without increasing anxiety.

Viewpoint

Study limitations include lack of postmortem verification for change in diagnosis and extensive diagnostic workup performed routinely at this tertiary referral center, which may have resulted in an underestimation of the value of amyloid PET. In addition, the tertiary referral center had a high proportion of young patients, often with complex clinical presentations, which may hinder generalizability to primary care and local memory clinics.

Nonetheless, this prospective diagnostic study suggests that amyloid PET, which has previously been validated only in research settings, may be feasible and useful to implement in daily clinical practice. In patients with and without dementia or mild cognitive impairment and subjective cognitive decline, amyloid-negative as well as amyloid-positive results had an important association with changes in diagnosis and treatment. Etiologic diagnosis changed for 25% of patients after amyloid PET, more often because of a negative than a positive PET scan result. In addition, PET scanning increased diagnostic confidence by an average of 10% and led to treatment changes in 24% of patients.

Several large studies of the clinical utility of amyloid PET are ongoing, including the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) study in the United States and the Amyloid imaging to prevent Alzheimer's disease (AMYPAD) study in Europe. These studies should help quantify the cost-effectiveness of amyloid imaging, but long-term follow-up is needed to determine how amyloid PET can help predict clinical outcomes. In the meantime, clinicians should realize that amyloid PET imaging is not a definitive test for clinical AD, as diagnosis requires a complete history and physical examination, structural CT or MRI imaging, and additional laboratory and cognitive workup as directed by a clinician experienced in dementia assessment.

Abstract

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