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.