TY - JOUR

T1 - Prognostic value of complementary biomarkers of neurodegeneration in a mixed memory clinic cohort

AU - Gramkow, Mathias Holsey

AU - Gjerum, Le

AU - Koikkalainen, Juha

AU - Lötjönen, Jyrki

AU - Law, Ian

AU - Hasselbalch, Steen Gregers

AU - Waldemar, Gunhild

AU - Frederiksen, Kristian Steen

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Magnetic resonance imaging

KW - Neurodegenerative disease

KW - Neuroimaging

KW - Positron-emission tomography

KW - Prognosis

KW - Tau

U2 - 10.7717/peerj.9498

DO - 10.7717/peerj.9498

M3 - Journal article

C2 - 32714664

AN - SCOPUS:85091344535

VL - 2020

JO - PeerJ

JF - PeerJ

SN - 2167-8359

IS - 7

M1 - e9498

ER -