Cognitive impairment was found in 30% of patients with amyotrophic lateral sclerosis in a study designed to assess the prevalence of cognitive involvement in what used to be considered a disease restricted to the motor system, according to Dr. Gregory A. Rippon and his associates.
In an editorial comment accompanying this report, Dr. Michael J. Strong of the University of Western Ontario, London, said that the 30% prevalence of dementia found in this study may actually underestimate the prevalence in the general population.
These subjects were evaluated “long before the institution of detailed tests of frontotemporal lobe dysfunction,” which would likely have detected dementia in more of them. Moreover, subjects with a family history of neurodegenerative diseases were excluded from this study, which again may have led to an underrepresentation of dementia cases, he said.
Dr. Rippon agreed that estimates must be considered unreliable at best, since the studies from which they were derived were flawed by small sample sizes, selection bias, widely varying definitions of cognitive impairment, and very different methods for assessing cognition.
As ALS is increasingly recognized as a multisystem neurodegenerative disorder, researchers have revised their estimates of cognitive involvement from 2% up to as much as 52%.
In what Dr. Rippon and his associates at Columbia University College of Physicians and Surgeons, New York, described as one of the largest studies of the issue to date, the researchers assessed 40 consecutively treated patients with classic ALS seen in a 1-year period at the university's Neurological Institute. These patients, along with 80 control subjects matched for age, sex, and education level, underwent a battery of neuropsychologic tests that evaluated learning and memory, executive function, attention and psychomotor speed, language, and visuospatial ability.
Twelve of the ALS patients (30%) showed cognitive impairment, including 9 (23%) who met the criteria for dementia.
Free recall, executive function, and naming were the areas of most severe impairment, while language comprehension was preserved and attention, processing speed, and visuospatial function remained normal.
This pattern is consistent with frontotemporal lobar dementia, the investigators said (Arch. Neurol. 2006;63:345–52).
Among the ALS patients, there was no difference between those with and without dementia in terms of age, sex, education level, site of symptom onset, emotional lability, subjective memory loss, or family history.
This finding is contrary to that of other researchers who suggested that patients with bulbar-onset ALS are particularly susceptible to dementia, Dr. Rippon and his associates noted.
ALS symptom severity did not seem to affect test performance. As a group, the ALS patients performed better than control subjects on most of the tasks tested.
Survival was the same in ALS patients with dementia as in those without dementia, but this study was underpowered to detect a survival difference of less than 3 years.
Previous studies have demonstrated a shorter survival time in ALS patients with frontotemporal dementia.
“Larger prospective studies with interval cognitive assessments would more fully address the possibility of differential survival,” they added.
In his editorial, Dr. Strong noted that the study's findings may provoke controversy over the clinical relevance of cognitive impairment in most ALS patients (Arch. Neurol. 2006;63:319–20).
Most cognitive impairment associated with ALS in the literature is “subtle,” not a fulminant dementia.