Background The increased risk of adverse drug reactions due to age-related altered pharmacokinetics and pharmacodynamics is a challenge when prescribing medications to older people, and especially among older people with major neurocognitive disorder who are particularly sensitive to drug effects. The aim of this study was to investigate the use of potential inappropriate medications (PIMs) in 2012 and 2017 among old people with major neurocognitive disorder. A secondary aim was to investigate factors associated with PIM use. Methods This register-study was based on the Swedish registry for cognitive/dementia disorders and the Swedish prescribed drug register. Criteria from the National Board of Health and Welfare were used to identify PIMs between 1 July–31 December 2012 and 1 July-–31 December 2017 among people ≥ 65 years. Drug use was defined as one or more filled prescriptions during each timeframe. Results The total use of PIMs declined significantly between 2012 (28.7%) and 2017 (21.7%). All PIMs and PIM groups declined between these years, except for antipsychotic drugs, which increased from 11.6% to 12.3%. The results from the multiple regression model found that PIM use was associated with younger age (OR: 0.97 CI: 0.96–0.97), a lower Mini Mental State Examination score (OR: 0.99 CI: 0.99–1.00), the use of multi-dispensed drugs (OR: 2.05 CI: 1.93–2.18), and compared to Alzheimer’s disease, with the subtypes dementia with Lewy bodies and Parkinson’s disease dementia (OR: 1.57 CI: 1.40–1.75), frontotemporal dementia (OR: 1.29 CI: 1.08–1.54) and vascular dementia (OR: 1.10 CI: 1.03–1.16). Conclusions Overall, the use of PIMs decreased between the years 2012 and 2017. The increase of antipsychotic drugs and the association between PIM use and multi-dispensed drugs warrant concern.