Relationship between ALS and the degree of cognitive impairment, markers of neurodegeneration and predictors for poor outcome. A prospective study.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease affecting motor neurons and may be associated with impaired cognition. Reliable prognostic factors for ALS patients are still missing.
METHODS: We prospectively included 67 patients, 42 women and 25 men, with clinically defined ALS. The disease severity was assessed and the patients underwent SPECT, lumbar puncture with determination of tau, hyperphosporylated tau (p-tau) and beta-amyloid and a detailed neuropsychological assessment using a standardized test battery. In patients who died, a detailed neuropathologic evaluation was performed.
RESULTS: The mean survival duration was 26.8 months. The delay between the first signs and confirmation of the diagnosis was 12.75 months. Cognitive impairment did not have an impact on the evolution of the disease. There was no correlation between neuropsychological and SPECT findings. Higher age at onset, more pronounced handicap and elevated beta-amyloid in the CSF were associated with shorter survival times. In brain tissue from nine of the deceased patients with ALS and dementia, all showed signs of comorbidity, six had hallmarks of frontotemporal lobar degeneration (FTLD) and three showed Alzheimer disease pathology. Brain tissues form 11 deceased ALS patients who did not show signs of dementia, had only changes compatible with a diagnosis of motor neuron disease.
CONCLUSION: In our prospective study, age, disease severity and CSF beta-amyloid levels taken together were a risk factor suggesting shorter survival times. Dementia is relatively frequent in ALS and may be a consequence of either FTLD or result from co-existing Alzheimer disease.