RT Journal Article
SR Electronic
T1 Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1909
OP 1914
DO 10.2967/jnumed.113.120378
VO 54
IS 11
A1 Lars Frings
A1 Timo S. Spehl
A1 Wolfgang A. Weber
A1 Michael Hüll
A1 Philipp T. Meyer
YR 2013
UL http://jnm.snmjournals.org/content/54/11/1909.abstract
AB Amyloid-β (Aβ) deposition is a pathologic hallmark of Alzheimer disease (AD). Although the typical spatial distribution pattern of Aβ deposition in early AD mainly involves regions distant from the hippocampus, the predominant clinical feature is impairment of hippocampus-dependent memory. We aimed at elucidating the relationship between neocortical Aβ load, regional neuronal function, and memory impairment. Methods: Thirty patients with early AD underwent combined 11C-Pittsburgh compound B (11C-PIB) and 18F-FDG PET and memory assessments. Composite measures of hemispheric Aβ load were calculated by volume-weighted mean values of neocortical 11C-PIB binding. Voxelwise 18F-FDG uptake was used as a measure of regional glucose metabolism reflecting neuronal activity. We investigated the relationship between left- and right-hemispheric Aβ load and regional glucose metabolism (voxelwise analyses). In addition, we assessed the correlations of hemispheric Aβ load (region-of-interest–based analyses) and regional glucose metabolism (voxelwise analysis) with memory performance. Analyses were corrected for age and sex. Results: Higher Aβ load in the left hemisphere was associated with reduced glucose metabolism of the left medial temporal lobe (MTL; r2 = 0.38) and correlated with worse wordlist recall (r = −0.37; partial correlation controlled for sex and age). Furthermore, wordlist recall correlated with regional glucose metabolism in the bilateral MTL and precuneus–posterior cingulate cortex and right lingual gyrus (r2 = 0.24). Conclusion: We demonstrated an association between the left-hemispheric Aβ load and impairment of the left MTL in AD at 2 different levels: regional hypometabolism and verbal memory. This correlation suggests that neocortical amyloid deposition is connected to or even drives neuronal dysfunction and neurodegeneration of the MTL, which is associated with impaired episodic memory processing as a clinical core symptom of AD.