Asymmetries of amyloid-β burden and neuronal dysfunction are positively correlated in Alzheimer's disease.
Clinical Alzheimer's disease affects both cerebral hemispheres to a similar degree in clinically typical cases. However, in atypical variants like logopenic progressive aphasia, neurodegeneration often presents asymmetrically. Yet, no in vivo imaging study has investigated whether lateralized neurodegeneration corresponds to lateralized amyloid-β burden. Therefore, using combined (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography, we explored whether asymmetric amyloid-β deposition in Alzheimer's disease is associated with asymmetric hypometabolism and clinical symptoms. From our database of patients who underwent positron emission tomography with both (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose (n = 132), we included all amyloid-positive patients with prodromal or mild-to-moderate Alzheimer's disease (n = 69). The relationship between (11)C-Pittsburgh compound B binding potential and (18)F-fluorodeoxyglucose uptake was assessed in atlas-based regions of interest covering the entire cerebral cortex. Lateralizations of amyloid-β and hypometabolism were tested for associations with each other and with type and severity of cognitive symptoms. Positive correlations between asymmetries of Pittsburgh compound B binding potential and hypometabolism were detected in 6 of 25 regions (angular gyrus, middle frontal gyrus, middle occipital gyrus, superior parietal gyrus, inferior and middle temporal gyrus), i.e. hypometabolism was more pronounced on the side of greater amyloid-β deposition (range: r = 0.41 to 0.53, all P < 0.001). Stronger leftward asymmetry of amyloid-β deposition was associated with more severe language impairment (P < 0.05), and stronger rightward asymmetry with more severe visuospatial impairment (at trend level, P = 0.073). Similarly, patients with predominance of language deficits showed more left-lateralized amyloid-β burden and hypometabolism than patients with predominant visuospatial impairment and vice versa in several cortical regions. Associations between amyloid-β deposition and hypometabolism or cognitive impairment were predominantly observed in brain regions with high amyloid-β load. The relationship between asymmetries of amyloid-β deposition and hypometabolism in cortical regions with high amyloid-β load is in line with the detrimental effect of amyloid-β burden on neuronal function. Asymmetries were also concordant with lateralized cognitive symptoms, indicating their clinical relevance.
1 Department of Nuclear Medicine, University Medical Centre, Freiburg, Germany 2 Centre of Geriatrics and Gerontology, University Medical Centre, Freiburg, Germany lars.frings@uniklinik-freiburg.de.
Lars
L
Frings
2 Centre of Geriatrics and Gerontology, University Medical Centre, Freiburg, Germany 3 Department of Psychiatry and Psychotherapy, University Medical Centre, Freiburg, Germany.
Sabine
S
Hellwig
1 Department of Nuclear Medicine, University Medical Centre, Freiburg, Germany.
Timo S
TS
Spehl
4 Department of Neurology, University Medical Centre, Freiburg, Germany.
Tobias
T
Bormann
5 Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Germany.
Ralph
R
Buchert
6 Centre for Medical Biometry and Medical Informatics, University Medical Centre, Freiburg, Germany.
Werner
W
Vach
3 Department of Psychiatry and Psychotherapy, University Medical Centre, Freiburg, Germany 7 Freiburg Brain Imaging, University Medical Centre Freiburg, Germany.
Lora
L
Minkova
2 Centre of Geriatrics and Gerontology, University Medical Centre, Freiburg, Germany.
Bernhard
B
Heimbach
2 Centre of Geriatrics and Gerontology, University Medical Centre, Freiburg, Germany 3 Department of Psychiatry and Psychotherapy, University Medical Centre, Freiburg, Germany 7 Freiburg Brain Imaging, University Medical Centre Freiburg, Germany.
Stefan
S
Klöppel
1 Department of Nuclear Medicine, University Medical Centre, Freiburg, Germany.
Philipp T
PT
Meyer
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003072:Cognition Disorders / Q000145:classification / Q000209:etiology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000000981:diagnostic imaging / Q000209:etiology*; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D019788:Fluorodeoxyglucose F18
Alzheimer’s disease; amyloid; biomarkers; hemispheric differences; positron emission tomography