Background Biomarkers of neurodegeneration, e.g. MRI brain atrophy and [¹⁸F]FDG-PET hypometabolism, are often evaluated in patients suspected of neurodegenerative disease. Objective Our primary objective was to investigate prognostic properties of atrophy and hypometabolism. Methods From March 2015-June 2016, 149 patients referred to a university hospital memory clinic were included. The primary outcome was progression/stable disease course as assessed by a clinician at 12 months follow-up. Intracohort defined z-scores of baseline MRI automatic quantified volume and [¹⁸F]FDG-PET standardized uptake value ratios were calculated for all unilaterally defined brain lobes and dichotomized as pronounced atrophy (+A)/ pronounced hypometabolism (+H) at z-score <0. A logistic regression model with progression status as the outcome was carried out with number of lobes with the patterns +A/-H, -A/+H, +A/+H respectively as predictors. The model was mutually adjusted along with adjustment for age and sex. A sensitivity analysis with a z-score dichotomization at −0.1 and −0.5 and dichotomization regarding number of lobes affected at one and three lobes was done. Results Median follow-up time was 420 days [IQR: 387-461 days] and 50 patients progressed. Patients with two or more lobes affected by the pattern +A/+H compared to patients with 0–1 lobes affected had a statistically significant increased risk of progression (odds ratio, 95 % confidence interval: 4.33, 1.90–9.86) in a multivariable model. The model was partially robust to the applied sensitivity analysis. Conclusion Combined atrophy and hypometabolism as assessed by MRI and [¹⁸F]FDG-PET in patients under suspicion of neurodegenerative disease predicts progression over 1 year.