Temporal association tracts and the breakdown of episodic memory in mild cognitive impairment

Abstract

Objective: To examine the pattern of association between microstructure of temporal lobe connections and the breakdown of episodic memory that is a core feature of mild cognitive impairment (MCI).Methods: Twenty-five individuals with MCI and 20 matched controls underwent diffusion MRI and cognitive assessment. Three temporal pathways were reconstructed by tractography: fornix, parahippocampal cingulum (PHC), and uncinate fasciculus. Tissue volume fraction-a tract-specific measure of atrophy-and microstructural measures were derived for each tract. To test specificity of associations, a comparison tract (corticospinal tract) and control cognitive domains were also examined.Results: In MCI, tissue volume fraction was reduced in the fornix. Axial and radial diffusivity were increased in uncinate and PHC implying more subtle microstructural change. In controls, tissue volume fraction in the fornix was the predominant correlate of free recall. In contrast, in MCI, the strongest relationship was with left PHC. Microstructure of uncinate and PHC also correlated with recognition memory, and recognition confidence, in MCI.Conclusions: Episodic memory in MCI is related to the structure of multiple temporal association pathways. These associations are not confined to the fornix, as they are in healthy young and older adults. In MCI, because of a compromised fornix, alternative pathways may contribute disproportionally to episodic memory performance. Breakdown of episodic memory is a core feature of mild cognitive impairment (MCI).1 Previous studies of MCI have focused on changes in the medial temporal lobe (MTL). However, the MTL is one node of wider networks for memory that include frontal and parietal lobes.2 The "extended hippocampal system" 3 incorporates the fornix-a large fiber tract composed mostly of connections associated with the hippocampal formation. 4 Alternatively, MTL-cortical interactions can be mediated by parahippocampal tracts including the uncinate fasciculus and the temporal portion of the cingulum bundle (parahippocampal cingulum [PHC]).In healthy older adults, the microstructure of the fornix is an established correlate of episodic memory performance. Fornix microstructure accounts for both age-related and age-independent variations in free recall.5 Recent diffusion MRI studies have found that fornix microstructure is compromised in MCI and Alzheimer disease. 6,7 Early damage might lead to engagement of alternative interactions, 8 so that episodic memory becomes disproportionately associated with microstructure of tracts other than the fornix. To test this hypothesis, diffusion MRI tractography was used to reconstruct the fornix, PHC, and uncinate in MCI and controls. Intrinsic microstructure and subtle atrophy were quantified separately 9,10 dealing with an important confound in MCI and aging.

Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment

“…Consistent with previous studies, MD, AxD and RD appeared to be more sensitive than FA for the detection of white matter microstructural changes (Acosta-Cabronero et al, 2010;Metzler-Baddeley et al, 2012). By looking at MD and AxD DTI scalars, we highlighted changes in white matter integrity in superior and posterior corona radiata in MCI A+N+.…”

“…Using NBS, network scale indices and node scale indices we did not highlight significant cluster impairment or connectome topological changes in MCI A+N-compared to CN A-N-or others MCI subgroups. In particular, MCI A+N-did not display alteration of the fornix, showing that even though fornix alterations have been described at the MCI stage, they are not present in all MCI patients (Madhavan et al, 2015;Metzler-Baddeley et al, 2012). term of conversion rate and cognitive deterioration, but discrepancies appear between studies (Caroli et al, 2015;Petersen et al, 2013;Vos et al, 2015;Wisse et al, 2015).…”

Sleep apnoea and the brain: a complex relationship

“…CPAP normalises these EEG changes 103 . 'Hypofunctioning' fornix likely alters DG neurogenesis and possibly also contributes to mild cognitive decline in OSA 104,105 . Reproduced with permission from 106,2 .…”

Topographic separation of fornical fibers associated with the anterior and posterior hippocampus in the human brain: An MRI‐diffusion study

“…Fibers associated with the anterior hippocampus were located laterally within the body of the fornix, whereas fibers associated with the posterior hippocampus were located medially. These findings pave the way for future work to determine whether these fornical subpopulations contribute to different cognitive functions and whether they are differentially affected by pathological conditions such as Mild Cognitive Impairment and Alzheimer's disease, both known to be associated with microstructural changes in the fornix (Fletcher et al., 2013; Metzler‐Baddeley, Hunt, et al., 2012; Sexton et al., 2010). The present findings offer, for example, a means to help determine whether there are differential rates of disruption in the white matter associated with the anterior and posterior hippocampus in these diseases.…”

“…Neuropsychological investigations of patients with fornix damage first highlighted the importance of this tract for episodic memory (Aggleton et al., 2000; D'Esposito, Verfaellie, Alexander, & Katz, 1995; Gaffan & Gaffan, 1991; Vann et al., 2008). Neuroimaging findings from healthy participants, as well as from patients with fornix pathology, have further established the importance of this tract for episodic memory (Metzler‐Baddeley, Jones, Belaroussi, Aggleton, & O'Sullivan, 2011; Metzler‐Baddeley, Hunt, et al., 2012; Oishi, Mielke, Albert, Lyketsos, & Mori, 2012; Zhuang, Sachdev, et al., 2012; Zhuang, Wen, et al., 2012). Despite the role of this tract in cognition, surprisingly little is understood about the organization of the fibers within the human fornix and how this might relate to its various connections.…”