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Abstract
Alzheimer's disease is the most common form of dementia. Its prodromal stage amnestic
mild cognitive impairment is characterized by deficits of anterograde episodic memory.
The development of standardized imaging inclusion criteria has to be regarded as a
prerequisite for future diagnostic systems. Moreover, successful treatment requires
isolating imaging markers predicting the disease. Accordingly, we conducted a systematic
and quantitative meta-analysis to reveal the prototypical neural correlates of Alzheimer's
disease and its prodromal stage. To prevent any a priori assumptions and enable a
data-driven approach only studies applying quantitative automated whole brain analysis
were included. Finally, 40 studies were identified involving 1351 patients and 1097
healthy control subjects reporting either atrophy or decreases in glucose utilization
and perfusion. The currently most sophisticated and best-validated of coordinate-based
voxel-wise meta-analyses was applied (anatomical likelihood estimates). The meta-analysis
reveals that early Alzheimer's disease affects structurally the (trans-)entorhinal
and hippocampal regions, functionally the inferior parietal lobules and precuneus.
Results further may suggest that atrophy in the (trans-)entorhinal area/hippocampus
and hypometabolism/hypoperfusion in the inferior parietal lobules predicts most reliably
the progression from amnestic mild cognitive impairment to Alzheimer's disease, whereas
changes in the posterior cingulate cortex and precuneus are unspecific. Fully developed
Alzheimer's disease involved additionally a frontomedian-thalamic network. In conclusion,
the meta-analysis characterizes the prototypical neural substrates of Alzheimer's
disease and its prodromal stage amnestic mild cognitive impairment. By isolating predictive
markers it enables successful treatment strategies in the future and contributes to
standardized imaging inclusion criteria for Alzheimer's disease as suggested for future
diagnostic systems.