A prospective study of cognitive impairment in ALS

To characterize prospectively the cognitive profile in ALS.

Clinically definite ALS patients (11 men, 2 women), age 39.9 to 74.0 years (mean age, 54.2 +/- 9.6 years; mean disease duration, 21.1 +/- 10.5 months) underwent neuropsychologic, language, and speech testing followed by MR 1H spectroscopy (4 T). Five spousal control subjects completed an identical protocol. Eight ALS patients participated in follow-up studies at a 6-month interval.

Relative to control subjects, ALS patients showed mild impairment in word generation, recognition memory (faces), and motor-free 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 cognitive impairment appeared more progressive over time. ALS patients demonstrated anomia on a confrontation naming test, with no significant problems following commands or repeating. Speech motor performance scores and intelligibility scores were not significantly different. No significant declines in forced vital capacity, forced expiratory volume, or peak expiratory flow rates were observed. Although normal at initial testing (T1), MR 1H spectroscopy demonstrated a reduction of the N-acetylaspartate/creatine (NAA/Cr) ratio in the nondominant precentral motor strip across the two testing intervals. In contrast, the NAA/Cr ratio obtained from the anterior cingulate gyrus at T1 was already reduced in bulbar-onset patients (p < 0.001), whereas no deficits were observed in limb-onset individuals in the same region.

Bulbar-onset ALS patients with cognitive impairments and neuronal loss in the anterior cingulate gyrus subsequently developed more profound neuropsychological dysfunction whereas both language and speech capabilities remained relatively preserved. Of note, the absence of bulbar signs did not predict an absence of cognitive decline.