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

Abstract

IMPORTANCE Previous studies have evaluated the diagnostic effect of amyloid positron emission tomography (PET) in selected research cohorts. However, these research populations do not reflect daily practice, thus hampering clinical implementation of amyloid imaging. OBJECTIVE To evaluate the association of amyloid PET with changes in diagnosis, diagnostic confidence, treatment, and patients' experiences in an unselected memory clinic cohort. DESIGN, SETTING, AND PARTICIPANTS Amyloid PET using fluoride-18 florbetaben was offered to 866 patients who visited the tertiary memory clinic at the VU University Medical Center between January 2015 and December 2016 as part of their routine diagnostic dementia workup. Of these patients, 476 (55%) were included, 32 (4%) were excluded, and 358 (41%) did not participate. To enrich this sample, 31 patients with mild cognitive impairment from the University Medical Center Utrecht memory clinic were included. For each patient, neurologists determined a preamyloid and postamyloid PET diagnosis that existed of both a clinical syndrome (dementia, mild cognitive impairment, or subjective cognitive decline) and a suspected etiology (Alzheimer disease [AD] or non-AD), with a confidence level ranging from 0% to 100%. In addition, the neurologist determined patient treatment in terms of ancillary investigations, medication, and care. Each patient received a clinical follow-up 1 year after being scanned. MAIN OUTCOMES AND MEASURES Primary outcome measures were post-PET changes in diagnosis, diagnostic confidence, and patient treatment. RESULTS Of the 507 patients (mean [SD] age, 65 (8) years; 201 women [39%]; mean [SD] Mini-Mental State Examination score, 25 [4]), 164 (32%) had AD dementia, 70 (14%) non-AD dementia, 114 (23%) mild cognitive impairment, and 159 (31%) subjective cognitive decline. Amyloid PET results were positive for 242 patients (48%). The suspected etiology changed for 125 patients (25%) after undergoing amyloid PET, more often due to a negative (82 of 265 [31%]) than a positive (43 of 242 [18%]) PET result (P < .01). Post-PET changes in suspected etiology occurred more frequently in patients older (>65 years) than younger (<65 years) than the typical age at onset of 65 years (74 of 257 [29%] vs 51 of 250 [20%]; P < .05). Mean diagnostic confidence (SD) increased from 80 (13) to 89 (13%) (P < .001). In 123 patients (24%), there was a change in patient treatment post-PET, mostly related to additional investigations and therapy. CONCLUSIONS AND RELEVANCE This prospective diagnostic study provides a bridge between validating amyloid PET in a research setting and implementing this diagnostic tool in daily clinical practice. Both amyloid-positive and amyloid-negative results had substantial associations with changes in diagnosis and treatment, both in patients with and without dementia.

Clinical applicability of diagnostic biomarkers in early‐onset cognitive impairment

“…The percentage of diagnostic/therapeutic change due to biomarkers is in accordance with other publications although most of them evaluated it in late‐onset AD . These data together reflect the important impact of AD biomarkers in daily clinical practice in the diagnostic work‐up of early‐onset cognitive impairment.…”

“…In our cohort, amyloid‐PET and CSF increased the diagnostic confidence. The improvement in diagnostic confidence by amyloid‐PET and its superiority over other biomarkers, such as FDG‐PET, has also been suggested . Previous studies also suggest that CSF biomarkers improve diagnostic confidence, with a high correlation with amyloid‐PET results .…”

Added value of amyloid PET in individualized risk predictions for MCI patients

“…The Harrell's C statistic was 0.73 (0.68-0.77) ( Table 2). Probabilities of progression ranged from 1% (0-2) in one year and 5% (3)(4)(5)(6)(7)(8)(9) in three years in young (age 60) APOE ε4 negative patients with a high MMSE score (30) to 23% (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) in one year and 62% in three years in older (age 80) APOE ε4 positive patients with a lower MMSE score (25).…”

“…Of note, including APOE ε4 count also resulted in similar model performances as the models with APOE ε4 presence and patient with one and two ε4 alleles were equally at risk. Based on demographic and basic clinical information only, this patient would have a probability to progress to ADdementia of 13% (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) in one year and 42% in three years. These progression probabilities are elevated in comparison with the baseline risk of 24% in 3 6 2 years in this cohort.…”

“…Taking into account the result of the amyloid PET scan but without looking at the information from the MRI, a negative amyloid PET would result in a decreased risk of 4% (2)(3)(4)(5)(6)(7)(8)(9) in one year and 15% in three years. In case of a positive amyloid PET, this risk would increase to 20% (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) in one year and 58% in three years.…”