PT - JOURNAL ARTICLE AU - Elise Koch AU - Kristina Johnell AU - Karolina Kauppi TI - Longitudinal effects of using and discontinuing CNS medications on cognitive functioning AID - 10.1101/2021.09.13.460082 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.09.13.460082 4099 - http://biorxiv.org/content/early/2021/09/16/2021.09.13.460082.short 4100 - http://biorxiv.org/content/early/2021/09/16/2021.09.13.460082.full AB - Background Medications acting on the central nervous system (CNS) have been associated with accelerated cognitive decline and increased risk of dementia. However, results are inconsistent and the longitudinal effects of CNS medications on cognitive performance are still not known.Methods Using longitudinal cognitive data from healthy adults aged 25-100 years (N = 2,475) from four test waves five years apart, we investigated both the link between use of CNS medications (opioids, antidepressants, anxiolytics, hypnotics and sedatives) on cognitive task performance (episodic memory, semantic memory, visuospatial ability) across 15 years, and the effect of discontinuing these medications in linear mixed effects models.Results We found that opioid use was associated with decline in visuospatial ability, whereas antidepressant use was associated with decline in semantic memory over 15 years. A link between drug discontinuation and cognitive improvement was seen for opioids, antidepressants as well as for anxiolytics, hypnotics and sedatives.Conclusions Although our results may be confounded by subjacent conditions, they suggest that long-term use of CNS medications may have domain-specific negative effects on cognitive performance over time, whereas the discontinuation of these medications may partly reverse these effects. These results open up for future studies that address subjacent conditions on cognition to develop a more complete understanding of the cognitive effects of CNS medications.Competing Interest StatementThe authors have declared no competing interest.