Detection Gap of Right-Asymmetric Neuronal Degeneration by CERAD Test Battery in Alzheimer’s Disease
Authors: Kreuzer Annika , Sauerbeck Julia , Scheifele Maximilian , Stockbauer Anna , Schönecker Sonja , Prix Catharina , Wlasich Elisabeth , Loosli Sandra V. , M. Kazmierczak Philipp , Unterrainer Marcus , Catak Cihan , Janowitz Daniel , Pogarell Oliver , Palleis Carla , Perneczky Robert , Albert Nathalie L. , Bartenstein Peter , Danek Adrian , Buerger Katharina , Levin Johannes , Zwergal Andreas , Rominger Axel , Brendel Matthias , Beyer Leonie 
Published: February 2021

Objectives: Asymmetric disease characteristics on neuroimaging are common in structural and functional imaging of neurodegenerative diseases, particularly in Alzheimer‘s disease (AD). However, a standardized clinical evaluation of asymmetric neuronal degeneration and its impact on clinical findings has only sporadically been investigated for F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG-PET). This study aimed to evaluate the impact of lateralized neuronal degeneration on the detection of AD by detailed clinical testing. Furthermore, we compared associations between clinical evaluation and lateralized neuronal degeneration between FDG-PET hypometabolism and hippocampal atrophy. Finally, we investigated if specific subtests show associations with lateralized neuronal degeneration.

Methods: One-hundred and forty-six patients with a clinical diagnosis of AD (age 71 ± 8) were investigated by FDG-PET and the “Consortium to Establish a Registry for Alzheimer’s disease” (CERAD) test battery. For assessment of neuronal degeneration, FDG-PET hypometabolism in brain regions typically affected in AD were graded by visual (3D-surface projections) and semiquantitative analysis. Asymmetry of the hippocampus (left-right) in magnetic resonance tomography (MRI) was rated visually by the Scheltens scale. Measures of asymmetry were calculated to quantify lateralized neuronal degeneration and asymmetry scores were subsequently correlated with CERAD.

Results: Asymmetry with left-dominant neuronal degeneration to FDG-PET was an independent predictor of cognitive impairment (visual: β = −0.288, p &lt; 0.001; semiquantitative: β = −0.451, p &lt; 0.001) when controlled for age, gender, years of education and total burden of neuronal degeneration, whereas hippocampal asymmetry to MRI was not (β = −0.034; p = 0.731). Direct comparison of CERAD-PET associations in cases with right- and left-lateralized neuronal degeneration estimated a detection gap of 2.7 years for right-lateralized cases. Left-hemispheric neuronal degeneration was significantly associated with the total CERAD score and multiple subscores, whereas only MMSE (semiquantitative: β = 0.429, p &lt; 0.001) and constructional praxis (semiquantitative: β = 0.292, p = 0.008) showed significant associations with right-hemispheric neuronal degeneration.

Conclusions: Asymmetry of deteriorated cerebral glucose metabolism has a significant impact on the coupling between neuronal degeneration and cognitive function. Right dominant neuronal degeneration shows a delayed detection by global CERAD testing and requires evaluation of specific subdomains of cognitive testing.