Abstract
The fornix is an integral white matter bundle located in the medial diencephalon and is part of the limbic structures. It serves a vital role in memory functions and as such has become the subject of recent research emphasis in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). As the characteristic pathological processes of AD progress, structural and functional changes to the medial temporal lobes and other regions become evident years before clinical symptoms are present. Though gray matter atrophy has been the most studied, degradation of white matter structures especially the fornix may precede these and has become detectable with use of diffusion tensor imaging (DTI) and other complimentary imaging techniques. Recent research utilizing DTI measurement of the fornix has shown good discriminability of diagnostic groups, particularly early and preclinical, as well as predictive power for incident MCI and AD. Stimulating and modulating fornix function by the way of DBS has been an exciting new area as pharmacological therapeutics has been slow to develop.
Highlights
Alzheimer’s disease (AD) is the most common neurodegenerative condition in aging
In a second study (Zhuang et al, 2012), the same group showed that when compared to normal subjects who remained stable over 2 years, those who converted to amnestic MCI (aMCI) had substantial reductions in white matter (WM) integrity in the fornix, parahippocampal gyrus WM, and cingulum while gray matter structures remained relatively intact
There is a small but growing body of research directed toward the structure and function of the fornix in Mild Cognitive Impairment (MCI) and AD
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative condition in aging. AD is a growing public health problem that is projected to reach epidemic proportions if disease-modifying therapies are not found. Most recent research in the area has focused on fornix microstructure as the measurement of WM integrity This renewed direction in imaging research of the fornix was based on the hypothesis that the earliest morphological changes occurred within medial temporal lobe gray matter, the hippocampus and entorhinal structures with secondary effect to the efferent outflow tract through the fornix and mammillary bodies (Braak and Braak, 1995; Cassel et al, 1997; Aggleton and Brown, 1999). Comparing both volumetric and microstructural variables including DTI anisotropy and diffusivity, they found significant group differences in the body of the fornix, left fimbria, and the superior longitudinal fasciculus These studies emphasize the importance of microstructural integrity of the limbic lobe and the fornix in predicting the progression/conversion from preclinical to clinical AD. One study (Zhuang et al, 2013) showed that when compared to
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