Cognitive deterioration affects a large proportion of multiple sclerosis (MS) patients, but it occurs also with healthy aging. The effects of aging on cognitive performance in MS have not been fully investigated yet.
By evaluating a large multicentric cohort of healthy controls (HC) and MS patients, we compared the age-related decline of cognitive functions occurring in HC and MS patients.
Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was evaluated in 301 healthy controls (HC) (150 females, age 18-76 years, mean education=14.9 years) and 664 MS patients (421 females; age 18-77 years; mean education=13.3 years; 536 relapsing-remitting and 128 progressive MS) recruited from 3 centers of the Italian Neuroimaging Network Initiative (INNI, www.inni-ms.org). BRB-N allowed to assess verbal memory (Selective Reminding Test [SRT]), visuospatial memory (10/36 Spatial Recall Test [SPART] and delayed-recall), information processing speed (Symbol Digit Modalities Test [SDMT], Paced Auditory Serial Addition Test [PASAT] 3” and 2”) and verbal fluency (Word List Generation [WLG]). Raw scores of each test were converted to Z-scores, based on HC’s cohort by running linear models to regress out the effects of sex, age, education and center. The residuals for both HC and MS patients were then divided by the HC’s error term. Linear models were built for investigating the association of standardized scores with age in MS patients.
In HC, scores of all the BRB-N tests except PASAT 3” and WLG declined significantly with aging (p from <0.0001 to 0.003). Compared to HC, MS patients showed significant worse estimated mean performances already from the age of 20 years in all BRB-N tests (p from <0.0001 to 0.003), except for SPART, SPART delayed-recall and PASAT 3”, whose estimated mean scores significantly worsened later in age (p from 0.03 to 0.04). MS patients showed also a steeper age-related decline of SPART, SPART delayed-recall, SDMT, PASAT 3”, PASAT 2” performances compared to HC (p from <0.0001 to 0.008). No differential effect of age compared to HC was detected in MS patients for WLG and SRT.
Cognitive deficits already affect young adult MS patients and progress faster during patients’ lifespan compared to healthy aging. A different susceptibility to age-effect exists in the cognitive tests currently used to assess cognition in MS patients. The accumulation of MS-related damage combined with brain aging may have synergic detrimental effects on cognitive performances of MS patients.
Funding. This project has been supported by a research grant from the Fondazione Italiana Sclerosi Multipla (FISM2018/S/3), and financed or co-financed with the ‘5 per mille’ public funding.