Memory-guided navigation in amyotrophic lateral sclerosis

Abstract

Background Previous studies have yielded inconsistent results about hippocampal involvement in non-demented patients with amyotrophic lateral sclerosis (ALS). We hypothesized that testing of memory-guided spatial navigation i.e., a highly hippocampus-dependent behaviour, might reveal behavioural correlates of hippocampal dysfunction in non-demented ALS patients. Methods We conducted a prospective study of spatial cognition in 43 non-demented ALS outpatients (11f, 32 m, mean age 60.0 years, mean disease duration 27.0 months, mean ALSFRS-R score 40.0) and 43 healthy controls (14f, 29 m, mean age 57.0 years). Participants were tested with a virtual memory-guided navigation task derived from animal research (“starmaze”) that has previously been used in studies of hippocampal function. Participants were further tested with neuropsychological tests of visuospatial memory (SPART, 10/36 Spatial Recall Test), fluency (5PT, five-point test) and orientation (PTSOT, Perspective Taking/Spatial Orientation Test). Results Patients successfully learned and navigated the starmaze from memory, both in conditions that forced memory of landmarks (success: patients 50.7%, controls 47.7%, p = 0.786) and memory of path sequences (success: patients 96.5%, controls 94.0%, p = 0.937). Measures of navigational efficacy (latency, path error and navigational uncertainty) did not differ between groups (p ≥ 0.546). Likewise, SPART, 5PT and PTSOT scores did not differ between groups (p ≥ 0.238). Conclusions This study found no behavioural correlate for hippocampal dysfunction in non-demented ALS patients. These findings support the view that the individual cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.

The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update

“…In a recent study from China, the ALSci group (49.5% of a total of 1015 ALS patients) tended to harbor more ALS-plus (extramotor) symptoms than the cognitively normal ALS group [36]. In non-demented ALS patients, no cognitive/behavioral correlate for hippocampal dysfunction was found [37].…”

Update on recent advances in amyotrophic lateral sclerosis

“…However, the neuropsychological deficits in ALS are extremely heterogeneous [ 135 , 138 ]. Originally construed as a disorder of behavior and executive impairment [ 142 ], the neuropsychological profile of ALS is now known also to be associated with alterations in language, social cognition (Table 1 ) and memory [ 143 ], albeit inconsistently [ 135 , 144 ]. The revised consensus criteria for the diagnosis of cognitive and behavioral dysfunction in ALS has led to re-conceptualization that neuropsychological deficits fall along a spectrum: from no impairment to mild cognitive impairment (ALSci), mild behavioral impairment (ALSbi), both (ALScbi) or ALS-FTD; thus embracing the concept of a frontotemporal spectrum disorder [ 135 ].…”