Episodic memory decline is one of the earliest cognitive signs of Alzheimer’s dementia however memory deficits are also common in clinically normal elderly. The ability to form memories for novel events is supported by brain regions within the medial temporal lobe including the entorhinal cortex and hippocampus. Tau neurofibrillary tangles in entorhinal cortex are commonly seen in old age, whilst the spread of tau pathology to neocortex in the progression towards Alzheimer’s disease requires the presence of Aβ plaques. Using tau- and Aβ specific PET (Positron Emission Tomography) tracers, we can assess the regional pattern and progression of Alzheimer’s pathology in the living human brain (Schöll, Maass et al, 2018; see Figure 1). Recent tau PET data indicate that entorhinal tau pathology is linked to episodic memory deficits in cognitively normal elderly, independent of Aβ burden (Maass et al., 2018; Figure 2). Does entorhinal tau pathology in the absence of Aβ pathology constitute early Alzheimer’s disease? Which factors induce the spread of tau tangles in the progression of the disease? How can some individuals maintain cognitive performance in the face of pathology? These are open question, which we hope to address in the future.
By combining molecular imaging with functional, structural and vascular MRI, our group aims to understand how specific memory pathways are disrupted in old age and Alzheimer’s disease. The use of high-resolution functional and structural MRI at 7T allows us to study memory networks and their dysfunction at the level of hippocampal-entorhinal subregions (Maass et al., 2014, Nat Commun). This will be crucial as different subregions subserve specific memory functions and show selective vulnerability to pathology. The use of multimodal imaging approaches will aid the development of more sensitive and disease-stage specific imaging and cognitive markers of Alzheimer’s disease.
Moreover, we want to better understand which factors underlie or impact brain plasticity to develop efficient exercise and cognitive intervention that promote healthy aging and prevent cognitive decline. Previous work at the DZNE has shown that vascular plasticity of the aged human hippocampus can improve episodic memory function (Maass et al., 2014, Mol Psychiatry). However, further research is necessary to understand the causes of individual variability in neurovascular plasticity.