Abstract: Background: This study was designed to evaluate the validity and reliability accuracy of the physical aspects of self-reported health related quality of life (HRQoL) over a long-term follow-up in MS patients at various levels of cognitive functioning.Even though it is recognized that HRQoL is a relevant endpoint in MS research, quality of life measures have not been readily accepted as outcome measures.As a full 50% of people with MS are estimated to have cognitive impairment, the reliability of self-report in this population must be examined.We aim to assess if decline in cognitive functioning effects the reliability of HRQoL self-report. Methods:A follow-up study of relapsing-remitting MS patients, who had participated in a two-year phase III study of interferon beta-la (Avonex), was conducted approximately eight years after their baseline visit.The intent of this follow-up was to determine the predictive value of the Multiple Sclerosis Functional Composite (MSFC) on MRI, clinical, and HRQoL parameters.These data will serve to ascertain the accuracy of HRQoL measures, using the Physical Dimension score of the Sickness Impact Profile (SIP) scale, over the eight-year follow-up.Cognitive functioning was assessed using the Paced Auditory Serial Addition Test (PASAT).Results: 172 phase III clinical trial patients were eligible for follow-up.Of those patients 137 had cognitive, EDSS, and SIP assessments at each assessment time.The PASAT was divided into quartiles.Spearman rank correlation coefficients were computed between SIP Physical Dimension scores and both EDSS and MSFC, stratified by PASAT quartiles, at baseline, two year, and follow-up.As patients progressed in their disease, their HRQoL also declined.The correlation coefficients were not significantly different across PASAT quartiles at any time point.Non-significant results were also obtained by regressing residuals, obtained from regressing the Physical Dimension on EDSS, on the PASAT scores at each time point.This is a good indication that even cognitively impaired individuals can accurately evaluate their HRQoL.