Abstract
BackgroundEpisodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging.Methodology/Principal Findings34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R2 = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R2 = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency.Conclusions/SignificanceThese findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.
Highlights
Cognitive impairment occurs in 30%–70% of multiple sclerosis (MS) patients and commonly manifests as disturbances in memory, complex attention, efficiency of information processing, executive functioning, and processing speed [1]
In particular we aim to identify the relative contribution of reduced hippocampal, thalamic and mammillary body volumes and reduced fornix tract integrity to performance in tests of visual memory/recall, verbal learning and recall, verbal recognition and a non-memory dependent test of verbal fluency
Mean fornix fractional anisotropy (FA) was strongly reduced in MS patients vs. controls (means adjusted for age and normalised fornix volume: 20.37 vs 0.46, F (1,55) = 34.6, P,.0005, Figure 3a)
Summary
Cognitive impairment occurs in 30%–70% of multiple sclerosis (MS) patients and commonly manifests as disturbances in memory, complex attention, efficiency of information processing, executive functioning, and processing speed [1]. Impairment of episodic memory is one of the most common cognitive deficits in MS, with particular involvement of recent memory and to a lesser extent immediate and remote memory [5] Both visual and verbal memory functions are affected being impaired in 56% and 34% of MS patients respectively [6]. Evidence from animal and human studies has shown that episodic memory is dependent on the extended hippocampal diencephalic system [8] This system consists of a series of direct and indirect parallel temporo-diencephalic pathways with damage to individual components leading to impairments in learning and recall, clinically manifesting as anterograde amnesia syndromes [9,10]. We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging
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