Positive PET Results and Hippocampal Volume Predict Progression From MCI to Dementia

PET scan of brain with Alzheimers
PET scan of brain with Alzheimers
An international team of investigators assessed the ability of flutemetamol F 18-labeled PET and other biomarkers to predict risk of clinical progression from amnestic mild cognitive impairment to probable Alzheimer disease.

Impaired cognitive function, low hippocampal volume, and positive results detected on flutemetamol F 18-labeled positron emission tomography (PET) β-amyloid brain scan can predict the risk for progression from amnestic mild cognitive impairment (aMCI) to clinical Alzheimer disease (AD) at up to 3 years, according to results of a study published in JAMA.

Patients aged ≥55 years who met criteria for aMCI were included in the analysis (n=232). At baseline, investigators performed a total of six 5-minute-frame β-amyloid PET brain scans following the intravenous administration of 185 MBq flutemetamol F 18. Patients also underwent local clinical evaluations every 6 months for 36 months. Interpreters of the scans were blinded to patient data and deemed results as either positive or negative based on instructions by the manufacturer. The study investigators also measured and estimated changes in patients’ hippocampal volume from baseline to follow-up.

The primary measure for this study was the time from PET scan to probable AD from baseline, with the addition of age, PET scan results, hippocampal volume, and aMCI stage at baseline representing the primary variables in the analysis. The positive and negative standardized uptake volume ratio values — derived from the bilateral frontal, anterior cingulate, parietal, lateral temporal, and posterior cingulate and precuneus cortical brain regions — were >1.56 and ≤1.56, respectively.

Approximately 42.2% of the study cohort had positive PET scan results vs 57.8% of participants whose results were deemed negative by the blinded investigators. By the end of the study, 36.2% of participants had received a diagnosis of probable AD. A greater proportion of patients with positive PET results were more likely to have a diagnosis of probable AD at 36 months compared with participants receiving negative PET results (53.6% vs 22.8%, respectively).

According to Cox proportional hazards logistic regression analysis, positive results on a β-amyloid scan alone were associated with a 2.5-times greater risk for progression to probable AD from aMCI when compared with negative results (hazard ratio [HR], 2.51; 95% CI, 1.57-3.99; P <.001). Low hippocampal volume (HR 5.60; 95% CI 3.14-9.98; P <.001) and poor cognitive status (HR 8.45; 95%, CI 4.40-16.24; P <.001) represented additional biomarkers associated with progression from aMCI to AD.

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The investigators noted that the study population with negative PET results had higher progression rates to AD compared with previously published research, suggesting the possibility of false-positive diagnoses and/or false-negative interpretations of PET scan results.

The evaluation of PET scan results, hippocampal volume, and cognitive status “could enhance the precision with which one can determine the likelihood of functional decline, which is of considerable importance to patients with mild cognitive symptoms.”


Wolk DA, Sadowsky C, Safirstein B, et al. Use of flutemetamol F 18-labeled positron emission tomography and other biomarkers to assess risk of clinical progression in patients with amnestic mild cognitive impairment [published online May 14, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.0894