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Amyloid PET scans may have clinical utility in patients with cognitive impairment

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Many pitfalls and unaddressed uses of amyloid PET

While amyloid PET scans have a clear role in research and in the right clinical setting they can support a suspected diagnosis of Alzheimer’s disease or help a clinician to choose between Alzheimer’s and a non-Alzheimer’s condition, their use can have pitfalls even at a diagnostically simplified level.

Dr. Richard J. Caselli

Dr. Richard J. Caselli

We know that amyloid positivity increases with age even in the cognitively unimpaired population, and it does a poor job of marking patients with actual cognitive deficits, unlike tau PET. And even if amyloid scan results are positive, patients may still harbor significant comorbid abnormalities that contribute to clinical severity. Amyloid PET scans also do not assess cholinergic integrity, and some patients with non-Alzheimer’s dementia also have cholinergic deficiencies that may derive the same benefit from treatment.

There are at least four patient populations in whom amyloid PET scans could potentially have clinical utility, but these are not addressed in the current debate over their use or in this study: patients with early-onset dementia, patients with normal pressure hydrocephalus, patients with rapidly progressive dementia in which the differential diagnosis includes some reversible conditions that may require a diagnostic brain biopsy, and rare patients with cerebral amyloid angiopathy who develop tumorlike accumulations that necessitate a brain biopsy for diagnosis.

Dr. Bryan K. Woodruff

Dr. Bryan K. Woodruff

Regardless of the current debate, the use of molecular imaging to identify the therapeutic target through either amyloid PET for amyloid-targeted therapies or tau PET for tau-targeted therapies will be unquestioned when disease-modifying therapy arrives.

Richard J. Caselli, MD, and Bryan K. Woodruff, MD, are with the department of neurology at the Mayo Clinic Arizona, Scottsdale. Their comments are derived from an editorial accompanying Dr. Boccardi and colleagues’ report (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3792). Dr. Caselli reported receiving research funding from Merck, and Dr. Woodruff reported receiving research funding from Genentech and Avid Pharmaceuticals.


 

Amyloid PET scans can affect diagnostic thinking and patient management when used alongside routine diagnostic work up in adults suspected of having Alzheimer’s disease, results from the multicenter, open-label Assessment of the Incremental Diagnostic Value of Florbetapir 18F Imaging in Patients with Cognitive Impairment (INDIA-FBP) study reveal.

The investigators, led by Marina Boccardi, PhD, of the LANVIE-Laboratory of Neuroimaging of Aging at the University of Geneva, conducted the study to provide evidence of whether amyloid PET imaging has diagnostic utility in patients suspected of having Alzheimer’s disease because amyloid PET scanning in its current state has debatable clinical value because of a lack of disease-modifying drugs available to treat Alzheimer’s and the expense of the scans.

The trial was published in this week’s edition of JAMA Neurology and Dr. Boccardi and her colleagues found that amyloid PET scans in 228 cognitively impaired Italian adults improved diagnostic confidence and led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease and in 25% (P = .02) of patients who had a non–Alzheimer’s disease–related dementia diagnosis. A positive scan resulted in a change in diagnosis to Alzheimer’s disease 72% of the time in patients with a prescan diagnosis of frontotemporal lobar degeneration (FTLD). Cognition-specific medications were initiated in 66% of previously untreated patients and were withdrawn in 33% of previously treated patients, results from the study showed (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3751).

The scans’ ability to provide additional information to change a diagnosis justifies their use, especially when considering “reports of adverse events in patients with FTLD treated with cholinesterase inhibitors and of ineffectiveness for cognitive impairment of vascular etiology,” the investigators wrote.

The use of amyloid PET scans to change a diagnosis to Alzheimer’s disease or confirm its diagnosis also allowed for earlier detection and intervention, gave patients an opportunity to be included in clinical trials, and allowed patients to make residential and financial arrangements at a time when they were still able to express their preference.

Anticipated results from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) and Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) studies will expand on the current observations on a larger scale as well as help to quantify the cost-effectiveness of amyloid PET in clinical routine practice, they said.

In the current study, a prescan diagnosis was made by clinicians who, at the time of the work-up, estimated diagnostic confidence and provided drug treatment. At the same time, an amyloid PET/CT scan was performed and the result was communicated to the clinicians upon work-up completion. Clinicians relied on the scan results for their final clinical diagnoses and identification of the most-appropriate treatment.

Amyloid PET scans are currently not reimbursed by the Centers for Medicare & Medicaid Services outside of their use in clinical trials.

This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.

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