Change in brain amyloid load and cognition in patients with amnestic mild cognitive impairment: a 3-year follow-up study.

BACKGROUND: Our aim was to investigate the discriminative value of 18F-Flutemetamol PET in longitudinal assessment of amyloid beta accumulation in amnestic mild cognitive impairment (aMCI) patients, in relation to longitudinal cognitive changes. METHODS: We investigated the change in 18F-Flutemetamol uptake and cognitive impairment in aMCI patients over time up to 3 years which enabled us to investigate possible association between changes in brain amyloid load and cognition over time. Thirty-four patients with aMCI (mean age 73.4 years, SD 6.6) were examined with 18F-Flutemetamol PET scan, brain MRI and cognitive tests at baseline and after 3-year follow-up or earlier if the patient had converted to Alzheimer´s disease (AD). 18F-Flutemetamol data were analyzed both with automated region-of-interest analysis and voxel-based statistical parametric mapping. RESULTS: 18F-flutemetamol uptake increased during the follow-up, and the increase was significantly higher in patients who were amyloid positive at baseline as compared to the amyloid-negative ones. At follow-up, there was a significant association between 18F-Flutemetamol uptake and MMSE, logical memory I (immediate recall), logical memory II (delayed recall) and verbal fluency. An association was seen between the increase in 18F-Flutemetamol uptake and decline in MMSE and logical memory I scores. CONCLUSIONS: In the early phase of aMCI, presence of amyloid pathology at baseline strongly predicted amyloid accumulation during follow-up, which was further paralleled by cognitive declines. Inversely, some of our patients remained amyloid negative also at the end of the study without significant change in 18F-Flutemetamol uptake or cognition. Future studies with longer follow-up are needed to distinguish whether the underlying pathophysiology of aMCI in such patients is other than AD.

Simple ratio analysis of 18F-fluorodopa uptake in striatal subregions separates patients with early Parkinson disease from healthy controls.

UNLABELLED: 6-(18)F-fluoro-l-dopa ((18)F-FDOPA) is widely used to investigate dopaminergic hypofunction, for instance, in Parkinson disease (PD). Conventionally, a 90-min scan with either a graphical or a metabolite-purified plasma input approach has been used for quantification. In the clinical setting, to increase compliance, especially in patients with more advanced disease, and to increase the efficacy of tracer and scanner time use, a shorter acquisition and a simple quantitative analysis are desirable. Taking into account the asymmetry of clinical symptoms and the uneven distribution of striatal dopaminergic hypofunction may also improve the use of (18)F-FDOPA PET in early disease detection. Therefore, we compared subregional striatal (18)F-FDOPA PET data from a large group of nonmedicated patients with early PD and a set of healthy elderly volunteers to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. METHODS: A total of 89 nonmedicated patients with early PD and 21 healthy volunteers were studied with (18)F-FDOPA PET, and both a region-to-reference (striatal-to-occipital) ratio (SOR) calculated from 75 to 90 min after injection and a graphical analysis of data calculated from 15 to 90 min after (18)F-FDOPA injection (yielding the influx constant [K(i)(ref)]) were used. RESULTS: Both SOR and K(i)(ref) values in the PD patients were lowest, relative to those in the healthy controls, in the posterior putamen contralateral to the side with predominant clinical symptoms. The contralateral posterior putamen showed the largest areas under the receiver operating characteristic (ROC) curve-0.994 for SOR and 0.998 for K(i)(ref)-indicating excellent separation of the PD and control groups. The caudate nucleus and the ventral striatum were less impressive in this respect. CONCLUSION: A single 15-min scan 75 min after tracer injection seems to be sufficient for separating patients with PD from healthy controls in a clinical research environment. This method represents a powerful and economical alternative for research on the disease mechanism and differential diagnosis.

A follow-up study on 6-[18F]fluoro-L-dopa uptake in early Parkinson's disease shows nonlinear progression in the putamen.

Sixteen subjects with de novo Parkinson's disease (PD) underwent three 6-[18F]fluoro-L-dopa (Fdopa) positron emission tomography (PET) scans during a follow-up time of 5 years (mean +/- SD 5.5 +/- 0.4 years) to study the progression of striatal dopaminergic hypofunction. Throughout the study, the smallest Fdopa uptake values were found in the dorso-caudal part of the putamen contralateral to the side with dominant motor symptoms. The rate of decline in Fdopa uptake in the contralateral putamen was faster in the beginning of the disease and slowed down as the disease progressed. The annual decline in Fdopa influx constant (Ki, unit x 10(-3) min(-1)) was on average 0.5 during the first 2 years and 0.2 during the subsequent 3 years (P = 0.002) in the contralateral putamen. In caudate, the rate of decline in Fdopa values was slower than in the putamen and did not change significantly during the follow-up time, annual decline in the contralateral caudate being 0.1 between baseline and 2 years and 0.3 between 2 and 5 years (P = 0.4). These results suggest that progression of putaminal dopaminergic hypofuncion in PD follows a nonlinear pattern at least in the contralateral side being faster in the beginning of the disease.