Is there a difference in regional read [18F]flutemetamol amyloid patterns between end-of-life subjects and those with amnestic mild cognitive impairment?

Visual interpretation of PET [18F]flutemetamol images relies on systematic review of five brain regions and is considered positive when an elevated signal is observed in at least one region. Amnestic mild cognitive impairment (aMCI) is an early clinical presentation of Alzheimer’s disease (AD); hence it is of interest to determine if the pattern of visually read regional positivity between end-of-life (EoL) patients with and without dementia and aMCI patients is different.

A total of 180 EoL patients with and without dementia (mean age 81 years, range 59 to 95 years) and 232 aMCI patients (mean age 71 years, range 53 to 91 years) were scanned following intravenous administration of 185-370 MBq [18F]flutemetamol. Images from both studies were read by two groups of five blinded readers who independently classified each of the five regions as either positive or negative. The majority interpretation made by at least three of the five readers was used as the imaging endpoint and compared with a composite standardized uptake value ratio (SUVR) analysis using a predetermined threshold.

Amyloid-positive images from 71 of 106 EoL patients coming to autopsy and from 97 aMCI patients were included. In the images from the EoL patients widespread deposition of amyloid was observed, with 76% of the images positive in all five regions and a further 20% positive in four regions. In the images from the aMCI patients, similar results were observed with 87% of the images positive in five regions and a further 5% positive in four regions. The mean SUVR of these positively read images was 2.24 (range 1.48 to 3.14) and 2.08 (range 1.28 to 3.04) in the autopsy and aMCI groups, respectively. There was 95.3% agreement between the visual reading and SUVR quantitation in the aMCI group and 90.4% agreement in the autopsy group.

Patients with aMCI showed a similar distribution of amyloid deposition determined by both visual reading and SUVR to that observed in patients with and without dementia coming to autopsy. Most of the aMCI patients, who are already within the AD continuum, had widespread amyloid deposition in terms of amount and topographical progression. Attempts to observe potential initial signs of amyloid deposition should focus on populations earlier in the dementia spectrum such as patients with subjective cognitive decline or even at-risk subjects with earlier stages of disease.