- Results from a new study suggest that the presence of cognitive impairment in the first 12 months after diagnosis is associated with a more rapid decline in muscle function in people with amyotrophic lateral sclerosis, while absence of early cognitive impairment is associated with slower functional decline.
- The findings illustrate the diversity (heterogeneity) in disease characteristics common in ALS and suggest that cognitive status in people with ALS may serve as a reliable marker for distinct disease subtypes.
- Practical implications include predicting disease progression after diagnosis, informing therapy development and improving clinical trial design.
The presence of cognitive impairment within the first year after a diagnosis of amyotrophic lateral sclerosis (ALS) may be associated with more rapid decline in muscle function, a team of researchers in Ireland has reported. Conversely, the absence of cognitive impairment within the first year appears to be associated with slower rates of functional decline.
The study results suggest that "the rate at which patients develop cognitive impairment and the pattern of cognitive deficits are variable in ALS, and that these are closely linked with the motor features of the illness," the investigators said. They noted that it will be necessary to confirm their findings in additional studies.
Approximately 50 percent of all people with ALS exhibit some symptoms of cognitive impairment and associated behavioral symptoms at some stage of their disease. In most people, ALS-associated cognitive impairment is so mild that only close family members may notice a difference. A small percentage of people with ALS meet the criteria for a formal diagnosis of frontotemporal dementia, or FTD. People who have both ALS and FTD are said to have ALS-FTD.
The findings, the team says, suggests a great deal of heterogeneity of disease characteristics in ALS and demonstrate that — along with site of symptom onset and rate of disease progression — cognitive status in people ALS may be a reliable, "important and clinically relevant" marker for distinct disease subtypes. Such a marker could have practical implications for predicting disease progression after diagnosis, and informing therapy development and clinical trial design.
The research team, led by Orla Hardiman at Beaumont Hospital and Trinity College in Dublin, Ireland, published its results online April 4, 2013, in Neurology. The full report is available for a fee: Cognitive Changes Predict Functional Decline in ALS A Population-Based Longitudinal Study.
About the study
Investigators conducted home visits to collect clinical and neuropsychological data on 186 people in Ireland who received a diagnosis of ALS during the study period (October 2006 to February 2011).
The study results did not include people who have ALS caused by a mutation in the C9ORF72 gene. Although 18 people with C9ORF72-related ALS were identified and observed, the small number precluded detailed analysis, the researchers wrote.
Visits began within 12 months of diagnosis and were conducted at six-month intervals until participants were no longer able to continue due to advanced physical disability or death.
Disease severity was assessed at each visit using the revised ALS Functional Rating Scale (ALSFRS-R). Cognitive function was measured using a comprehensive battery of neuropsychological tasks. Information on behavior was obtained via direct evaluation of the patients and information received from caregivers.
Of the 186 people who participated in the study, 22 were found to have ALS-FTD. The investigators classified the remaining participants into three subgroups:
- 94 had no cognitive abnormality;
- 47 had executive dysfunction (problems with completing tasks that require complex planning, forethought or organization); and
- 23 had nonexecutive dysfunction (abnormalities unrelated to executive function, such as language dysfunction or impaired memory).
About the results
Data showed that cognitive impairment — particularly difficulties with executive dysfunction — that appeared within the first 12 months after receiving an ALS diagnosis was associated with higher study dropout rates and faster decline in motor progression. This finding also was true for the appearance of ALS-FTD within the first 12 months.
- Study participants in whom no cognitive abnormality was detected at baseline (the first study visit) had slower rates of motor decline and a tendency to remain "cognitively intact."
- Participants who showed executive dysfunction at the first visit had more aggressive disease progression and experienced a spread of impairment over time.
- Decline in cognitive function was faster in those who showed signs of cognitive impairment at baseline.
- Four out of five study participants who initially presented with executive dysfunction later developed nonexecutive dysfunction as well. However, only one out of five patients who showed signs of nonexecutive dysfunction at the first home visit later developed executive dysfunction. The majority of these changes had occurred before the first six-month follow-up.
In limited analysis of people with C9ORF72-associated ALS, data showed that proportionally more of them had developed new-onset cognitive impairment by the first six-month follow-up visit than people with other forms of ALS. But the number of C9ORF72-affected participants was too small for detailed analysis.
For more information
To learn more about cognitive impairment in ALS, read: