The cognitive profile of amyotrophic lateral sclerosis: A meta-analysis.

We aimed to clarify the profile of cognitive impairment in ALS, by meta-analysis of published studies. Criteria for inclusion were: ALS diagnosed according to El Escorial criteria; control group matched for age and education; correction for bias due to motor impairment or dysarthria; no dementia in patients and controls. Effect sizes reflecting a difference in neuropsychological performance between ALS patients and controls were calculated for 12 cognitive domains. The effect of demographic and clinical variables (age, disease duration, site of onset) on cognition was assessed in a moderator analysis. Of 48 eligible articles, 16 studies encompassing 554 ALS patients were included. Significant effect sizes were found for the Mini Mental State Examination (d=0.8), immediate verbal memory (d=0.5), visual memory (d=0.4), fluency (d=0.5), psychomotor speed (d=0.7), language (d=0.5) and executive functioning (d=0.3). The results of the latter three domains are less reliable due to the possibility of publication bias. Psychomotor speed, and to a lesser extent fluency, may have been influenced by motor impairment, despite attempts to correct for motor slowness. In conclusion, the diversity of cognitive problems in ALS seems greater than was previously thought. ALS patients may suffer from cognitive impairment in multiple domains, including memory dysfunction.