Kurzfassung

Hippocampal atrophy is a major structural imaging finding in early Alzheimer’s disease (AD). Corresponding to the neuropathological finding of early neurofibrillary tangle accumulation within the CA1 subfield recent studies showed pronounced volume loss within the lateral hippocampal regions in mild cognitive impairment and mild AD. On the other hand there is increasing evidence from neuroanatomical and fMRI studies that the anterior hippocampus plays a crucial role in the formation of...Hippocampal atrophy is a major structural imaging finding in early Alzheimer’s disease (AD). Corresponding to the neuropathological finding of early neurofibrillary tangle accumulation within the CA1 subfield recent studies showed pronounced volume loss within the lateral hippocampal regions in mild cognitive impairment and mild AD. On the other hand there is increasing evidence from neuroanatomical and fMRI studies that the anterior hippocampus plays a crucial role in the formation of memories. Using diffusion-tensor imaging (DTI) we recently showed that pathologically increased diffusivity within the left anterior hippocampus was significantly correlated to disturbed episodic memory function in early AD.
Aim of the proposed study is a multimodal assessment of hippocampal function and structure in early AD patients. By definition patients with early AD must fulfil the NINCDS-ADRCA criteria of probable AD , achieve a global Clinical Dementia Rating (CDR) score of 0.5 or 1 and a MMSE raw score ³ 23. Using a 3 Tesla scanner hippocampal BOLD signal responses will be assessed during an associative learning task (encoding and retrieval) in 20 patients and 20 age- and education-matched healthy controls. The paradigm consists of a block of associative encoding of picture pairs, of face – name – pairs, and of word pairs, a block of retrieval of the encoded pairs, and an interposed measurement of the so-called “default-mode network activity” (complete rest vs. counting with eyes open).In addition global and regional hippocampal volumes and diffusivity will be determined to test the hypotheses that (1) structural disturbances in the left anterior hippocampus that can be detected sensitively by volume loss and/or increased diffusivity are negatively associated with memory performance and hippocampal activation in early AD patients and (2) patients with relatively good preserved encoding function (median division) show normal left anterior hippocampal BOLD response and a relatively unimpaired left anterior hippocampal structure compared to patients with more severely impaired memory or normal controls. Moreover, default network activity using independent component analysis and extra-hippocampal BOLD signal response will be assessed that both might identify regional dysfunction as well as compensatory capability in early AD patients with anterior hippocampal lesions. Finally, the influence of functional and structural connectivity regarding the hippocampus and the posterior cingulate gyrus, a second neuronal substrate necessary for memory performance, especially retrieval, will be investigated by fMRI and fiber tractography.
This investigation should enlighten the relations of functional and structural substrates of memory impairment in early AD.
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