A prospective study of cognitive impairment in ALS

Objective: To characterize prospectively the cognitive profile in ALS. Meth ods: Clinically definite ALS patients (11 men, 2 women), age 39.9 to 74.0 y ears (mean age, 54.2 +/- 9.6 years; mean disease duration, 21.1 +/- 10.5 mo nths) underwent neuropsychologic, language, and speech testing followed by MR H-1 spectroscopy (4 T). Five spousal control subjects completed an ident ical protocol. Eight ALS patients participated in follow-up studies at a 6- month interval. Results: Relative to control subjects, ALS patients showed mild impairment in word generation, recognition memory (faces), and motor-f ree visual perception. Bulbar-onset patients showed greater impairment in a number of measures (working memory, problem solving/cognitive flexibility, visual perception, and recognition memory for words and faces), and cognit ive impairment appeared more progressive over time. ALS patients demonstrat ed anemia on a confrontation naming test, with no significant problems foll owing commands or repeating. Speech motor performance scores and intelligib ility scores were not significantly different. No significant declines in f orced vital capacity, forced expiratory volume, or peak expiratory flow rat es were observed. Although normal at initial testing (T1), MR H-1 spectrosc opy demonstrated a reduction of the N-acetylaspartate/creatine (NAA/Cr) rat io in the nondominant precentral motor strip across the two testing interva ls. In contrast, the NAA/Cr ratio obtained from-the anterior cingulate gyru s at T1 was already reduced in bulbar-onset patients (p < 0.001), whereas n o deficits were observed in limb-onset individuals in the same region. Conc lusions: Bulbar-onset ALS patients with cognitive impairments and neuronal loss in the anterior cingulate gyrus subsequently developed more profound n europsychological dysfunction whereas both language and speech capabilities remained relatively preserved. Of note, the absence of bulbar signs did no t predict an absence of cognitive decline.