Abstract
Memory impairment in motor neuron disease (MND) is still an underrecognized feature and has traditionally been attributed to executive dysfunction. Here, we investigate the rate of memory impairment in a longitudinal cohort of MND patients, its relationship to other cognitive functions and the underlying neuroanatomical correlates. 142 patients with MND and 99 healthy controls (HC) underwent comprehensive neuropsychological testing and structural MRI at 3T up to four times over a period of 18 months. Linear-mixed effects models were fitted to identify changes at baseline and over time in episodic memory function (learning, immediate and delayed recall, recognition), composed cognitive scores (memory, verbal fluency, executive function), and memory-related structural brain regions (hippocampus, entorhinal cortex, parahippocampal gyrus). Associations between episodic memory performance and volumetric or cortical thickness changes of these regions were computed using Pearson's r. Learning, immediate and delayed recall, as well as recognition performance were significantly reduced in MND when compared to controls at baseline. Performances in these subtests improved over time although MND showed less improvement than controls. This relationship did not change when only "classical" ALS patients were considered. Patients with MND showed thinning of the right parahippocampal gyrus (PhG) in comparison to controls that was progressing over time. Bilateral hippocampal atrophy was observed in MND patients with memory impairment after splitting the group according to their overall episodic memory performance, with the right hippocampus shrinking over time. In MND patients, the bilateral hippocampal atrophy was associated with impairment in learning, recall, and recognition at baseline. In contrast, left PhG thinning was associated with a poorer learning performance. These results show that episodic memory impairment in MND is a frequent cognitive dysfunction. Since deficits are not clearly declining with disease course, an early involvement of this cognitive domain in the disease seems probable. The memory performance-dependent atrophy of the hippocampus and PhG provide evidence for a widespread involvement of these non-motor cortical areas in disease pathology.