Amyloid-beta Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

作者：Frings Lars^*; Spehl Timo S; Weber Wolfgang A; Huell Michael; Meyer Philipp T

来源：Journal of Nuclear Medicine, 2013, 54(11): 1909-1914.

DOI：10.2967/jnumed.113.120378

• Alzheimer's disease
• episodic memory
• positron emission tomography
• Pittsburgh compound beta
• amyloid

Amyloid-beta (A beta) deposition is a pathologic hallmark of Alzheimer disease (AD). Although the typical spatial distribution pattern of A beta 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 A beta load, regional neuronal function, and memory impairment. Methods: Thirty patients with early AD underwent combined C-11-Pittsburgh compound B (C-11-PIB) and F-18-FDG PET and memory assessments. Composite measures of hemispheric A beta load were calculated by volume-weighted mean values of neocortical C-11-PIB binding. Voxelwise F-18-FDG uptake was used as a measure of regional glucose metabolism reflecting neuronal activity. We investigated the relationship between left-and right-hemispheric A beta load and regional glucose metabolism (voxelwise analyses). In addition, we assessed the correlations of hemispheric A beta load (region-ofinterest- based analyses) and regional glucose metabolism (voxelwise analysis) with memory performance. Analyses were corrected for age and sex. Results: Higher A beta load in the left hemisphere was associated with reduced glucose metabolism of the left medial temporal lobe (MTL; r(2) = 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 (r(2) = 0.24). Conclusion: We demonstrated an association between the left-hemispheric A beta 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.

• 出版日期2013-11-1