Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Alzheimers Res Ther . 2026 Feb 27;18:72. doi: 10.1186/s13195-026-01988-8 Search in PMC Search in PubMed View in NLM Catalog Add to search Polypharmacy in people with dementia: a nationwide Danish study Nelsan Pourhadi Nelsan Pourhadi 1 Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Inge Lehmanns Vej, entrance 8, Copenhagen, 2100 Denmark 2 Department of Neurology, Bispebjerg Hospital, Copenhagen, 2400 Denmark Find articles by Nelsan Pourhadi 1, 2, ✉ , Christina Jensen-Dahm Christina Jensen-Dahm 1 Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Inge Lehmanns Vej, entrance 8, Copenhagen, 2100 Denmark 3 Department of Clinical Medicine, University of Copenhagen, Copenhagen, 2100 Denmark Find articles by Christina Jensen-Dahm 1, 3 , Thomas Munk Laursen Thomas Munk Laursen 4 National Centre for Register-Based Research, Aarhus University, Aarhus, 8000 Denmark Find articles by Thomas Munk Laursen 4 , Christiane Gasse Christiane Gasse 5 Department of Affective Disorders, Aarhus University Hospital Psychiatry, Aarhus, 8200 Denmark 6 Department of Clinical Medicine, Aarhus University, Aarhus, 8000 Denmark Find articles by Christiane Gasse 5, 6 , Gunhild Waldemar Gunhild Waldemar 1 Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Inge Lehmanns Vej, entrance 8, Copenhagen, 2100 Denmark 3 Department of Clinical Medicine, University of Copenhagen, Copenhagen, 2100 Denmark Find articles by Gunhild Waldemar 1, 3 , Janet Janbek Janet Janbek 1 Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Inge Lehmanns Vej, entrance 8, Copenhagen, 2100 Denmark Find articles by Janet Janbek 1 Author information Article notes Copyright and License information 1 Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Inge Lehmanns Vej, entrance 8, Copenhagen, 2100 Denmark 2 Department of Neurology, Bispebjerg Hospital, Copenhagen, 2400 Denmark 3 Department of Clinical Medicine, University of Copenhagen, Copenhagen, 2100 Denmark 4 National Centre for Register-Based Research, Aarhus University, Aarhus, 8000 Denmark 5 Department of Affective Disorders, Aarhus University Hospital Psychiatry, Aarhus, 8200 Denmark 6 Department of Clinical Medicine, Aarhus University, Aarhus, 8000 Denmark ✉ Corresponding author. Received 2025 Aug 27; Accepted 2026 Feb 12; Collection date 2026. © The Author(s) 2026 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ . PMC Copyright notice PMCID: PMC13049764 PMID: 41761361 Abstract Background Polypharmacy, particularly central nervous system (CNS)-active polypharmacy, is widespread in individuals with dementia and may accelerate cognitive decline and increase hospitalization and mortality risks. Identifying the extent and trends of polypharmacy is essential for optimizing medication use in this vulnerable population. We examined the prevalence, time trends, and adjusted odds of polypharmacy and CNS-active polypharmacy in older adults with dementia compared to those without dementia. Methods The study was a series of nationwide cross-sectional population-based studies based on the national Danish registers. All Danish residents aged ≥ 65 years ( N = 1,184,366) were included as of January 1, 2022, including 38,252 individuals with dementia. Dementia, along with somatic and psychiatric comorbidities, was identified through hospital diagnoses, while medication use was assessed based on filled prescriptions. Historical trends were examined from 2012 to 2022. Dementia was based on diagnoses or dementia-specific medication use. Polypharmacy was defined as concurrent use of ≥ 5 medications, and CNS-active polypharmacy as ≥ 3 CNS-active drugs (antidepressants, antipsychotics, antiepileptics, anxiolytics, hypnotics, or opioids). Age- and sex-standardized prevalences were calculated by direct standardization. Adjusted odds ratios (ORs) for polypharmacy and CNS-active polypharmacy were estimated using logistic regression. Results Among 1,184,366 individuals in 2022, 38,252 (3.2%) had dementia (59.4% female) with median age of 82 years (IQR, 77–87 years). Polypharmacy was identified in 56.2% of those with dementia, compared to 35.6% without dementia, fully adjusted OR, 1.47 (95% CI, 1.44–1.51). CNS-active polypharmacy was observed in 10.1% of individuals with dementia and 2.3% of those without, fully adjusted OR, 2.70 (95% CI, 2.59–2.81). Cardiovascular medications were the most frequently used among individuals with dementia experiencing polypharmacy. For CNS-active polypharmacy, antidepressants, opioids, and antipsychotics were most common. Between 2012 and 2022, polypharmacy prevalence in dementia declined from 65.1% to 56.2%, and CNS-active polypharmacy from 15.0% to 10.1%. Patterns differed by living situation with dementia being linked to higher polypharmacy in community-dwelling individuals but lower in nursing homes. Conclusions While polypharmacy and CNS-active polypharmacy in dementia have declined over the past decade, likely influenced by targeted safer prescribing initiatives, they remain disproportionately high in individuals with dementia. The findings reinforce the need for continued interventions to support safe medication use in dementia care. Supplementary Information The online version contains supplementary material available at 10.1186/s13195-026-01988-8. Keywords: Dementia, Polypharmacy, Medication use, Epidemiology, Nursing home Background Polypharmacy among older adults, commonly defined as simultaneous use of five or more drugs, is associated with several adverse outcomes including hospitalization, increased mortality, and drug-drug interactions [ 1 , 2 ]. Although prescribed in accordance with labelled indications, the harms of some pharmacological products may outweigh the benefits, particularly in older adults with dementia [ 2 , 3 ]. Additionally, dementia complicates the assessment and reporting of both the effectiveness and side effects of medications [ 4 ]. The high prevalence of multimorbidity and polypharmacy in people with dementia coupled with increased vulnerability to the risks of polypharmacy give rise to clinical and public health challenges [ 2 , 5 ]. People with dementia often have somatic and psychiatric comorbidities leading to complex medical and psychosocial needs. Despite limited evidence of efficacy, behavioral and psychological symptoms are often treated pharmacologically with central nervous system (CNS)-active drugs e.g., psychotropic medications. CNS-active polypharmacy among people with dementia may further worsen cognition and accelerate the progression of symptoms [ 6 ]. Additionally, anticholinergics and sedatives have been associated with increased mortality and hospitalization among people with dementia [ 7 ]. Although, it is not well established whether these risks exceed those among individuals without dementia, interventions to optimize prescribing practices are crucial, especially for this vulnerable population [ 8 ]. Nationwide data on the presence of polypharmacy and CNS-active polypharmacy in adults with dementia is limited. In Denmark, from 2000 to 2015, the use of potentially inappropriate medication declined among older adults [ 9 ]. Nonetheless, in 2014, 62.6% of individuals with dementia were exposed to polypharmacy versus 35.1% in individuals without dementia [ 10 ]. However, it is unknown whether this is entirely explained by differential burden of somatic and psychiatric comorbidity or whether subsequent recommendations on safe prescribing including non-pharmacological practices [ 11 , 12 ] have altered the presence of polypharmacy and CNS-active polypharmacy [ 8 , 13 – 16 ]. To update previous findings, the aim of this nationwide cross-sectional study of the Danish population aged 65 + years was to investigate the prevalence and odds of polypharmacy and CNS-active polypharmacy considering burden of disease in individuals with dementia compared to individuals without dementia. Additionally, we investigated time trends of polypharmacy levels, the influence of living situation (community-dwelling or nursing home), and the most frequently used drugs in the older adult Danish population. Methods Study design and population Using the national Danish registers, we conducted a nationwide cross-sectional study of the Danish population. The study population comprised a cohort of all Danish residents aged 65 years and above at baseline on 1 January 2022. A history of young onset dementia before age 65 years was an exclusion criterion due to the focus on late-onset all-cause dementia. Individuals immigrating to Denmark after 1 January 2022 were not included. Individuals who died or emigrated during the study period from 1 January 2022 to 31 March 2022 were included in the study population. This study was based on national register data from the (1) Danish National Patient Register [ 17 ], (2) Danish Psychiatric Central Research Register [ 18 ], (3) Danish National Prescription Register [ 19 ], (4) Danish Education Register [ 20 ], and (5) Care Home Data [ 21 ]. In Denmark, all residents are assigned a unique personal identification number registered in the Civil Registration System [ 22 ] allowing for reliable linkage of data across the registers. Dementia Dementia status was assessed for the study population on 1 April 2022 (end of study period). People with dementia included individuals with prevalent late-onset all-cause dementia (from age 65 + years) registered before 1 April 2022. Dementia was defined as the first date of a registered dementia syndrome diagnosis or treatment with dementia-specific medication (Appendix Table 1). Dementia syndrome diagnoses in Danish hospital registers have high validity with a positive predictive value of 85.8% [ 23 ]. Polypharmacy Information on use of pharmacological products in the study population was drawn from the National Danish Prescription Register providing complete data on all prescriptions redeemed from Danish community pharmacies since 1995. Drug use was identified through the specific Anatomical Therapeutic Chemical (ATC) codes. Other than the ATC-code, prescription data further included the date of purchase, package/unit size, and generic drug name. Polypharmacy was defined as prescription redemption of five or more different drugs (ATC drug substance level 5) within the first quarter of 2022 (1 January to 31 March). A three-month observation window was selected to maintain comparability with previous Danish studies using the same timeframe to estimate concurrently used medications [ 1 , 10 , 24 ]. Although shorter windows may underestimate infrequent prescription redemptions, longer windows may capture medications not used simultaneously. To evaluate the robustness of this definition, we also performed a 6-month sensitivity analysis. Polypharmacy included all filled prescriptions provided by the prescription register except for anti-dementia medication which were excluded. CNS-active polypharmacy was defined as prescription redemption of three or more different CNS-active drugs (ATC level 5) within the first quarter of 2022. This definition corresponds to a previous study on CNS-active polypharmacy among individuals with dementia [ 25 ]. CNS-active drugs included antidepressants (N06A), antipsychotics (N05A), antiepileptics (N03A), anxiolytics (N05B), hypnotics (N05C), and opioids (N02A, N07BC). Comorbidity and other variables Sociodemographic variables comprised age, sex, educational level (elementary/secondary school; vocational education; university education) and living situation (community dwelling; nursing home). The presence of chronic somatic comorbidity as defined in diagnoses of the Charlson Comorbidity Index (excluding dementia diagnoses) [ 26 ] and psychiatric comorbidity was assessed from International Classification of Diseases 8th and 10th revision (ICD-8 and ICD-10) diagnoses provided by the Danish National Patient Register and the Danish Psychiatric Central Research Register (Appendix Table 1). Psychiatric comorbidities included psychotic disorders, mood disorders, and anxiety disorders. Variables were assessed at baseline on 1 January 2022. Data analysis Descriptive statistics were applied to evaluate polypharmacy, CNS-active polypharmacy, and categorical and continuous characteristics. The polypharmacy period prevalence proportion was calculated from the number of individuals with polypharmacy during the first quarter of 2022 as the numerator, and the total number of individuals as the denominator. Calculations were performed separately for polypharmacy and CNS-active polypharmacy in people with and without dementia. The age- and sex-standardized period prevalence proportions in people with dementia, and confidence intervals (CI) were calculated by direct standardization according to the age- and sex- distribution in people without dementia. Logistic regression analyses providing odds ratios (ORs) and 95% CIs were used to compare the odds of polypharmacy in people with dementia compared with those without. Three models were applied: (1) crude model, (2) adjustment for age, sex, and education, (3) further adjustment for CCI score and psychiatric disorders. Among individuals with dementia, the most frequently used pharmacological subgroups (ATC level 3) and the single most frequently used specific generic drug within each pharmacological subgroup were identified and ranked for all drugs in people with polypharmacy and for CNS-active drugs in people with CNS-active polypharmacy. We additionally studied time trends in the period prevalence proportion of polypharmacy and CNS-active polypharmacy by performing individual cross-sectional analyses for the years 2012–2021 in independent populations in the same age groups and with the same inclusion/exclusion criteria as the main study population, requiring individuals to be alive and reside in Denmark on 1 January of the respective year. Thus, individuals may contribute to multiple annual cross-sectional populations. Furthermore, the prevalence and adjusted ORs of polypharmacy in 2022 was calculated stratified by living situation (community dwelling; nursing home). A sensitivity analysis investigated polypharmacy defined from prescriptions within the first six months of 2022 instead of the first three months. Another sensitivity analysis investigated polypharmacy additionally defined from prescriptions on ATC level 4 instead of level 5. Data were processed and analyzed using SAS software version 9.4 (SAS Institute) and R statistical software (R Core Team, 2020) [ 27 ]. Results Among the entire study population of 1,184,366 individuals aged 65 + years, 38,252 (3.2%) had dementia of which 59.4% were female. The median age at baseline (IQR) was 82 years (77–87 years) for people with dementia and 74 years (70–80 years) for people without dementia. Overall, people with dementia had a higher prevalence of somatic and psychiatric comorbidity. Detailed characteristics across the study population are shown in Table 1 . Table 1. Baseline characteristics of the study population according to dementia status Variable All-cause dementia ( n = 38,252) No dementia ( n = 1,146,114) Sex, No. (%) Female 22,718 (59.4) 616,278 (53.8) Male 15,534 (40.6) 529,836 (46.2) Age, median (IQR), y 82 (77–87) 74 (70–80) Age, No. (%), y 65–70 937 (2.4) 286,412 (25.0) 70–75 3,879 (10.1) 296,787 (25.9) 75–80 8,560 (22.4) 275,514 (24.0) 80–85 9,972 (26.1) 158,786 (13.9) 85+ 14,904 (39.0) 128,615 (11.2) Education, No. (%) Elementary/secondary school 15,882 (41.5) 361,218 (31.5) Vocational education 14,926 (39.0) 509,571 (44.5) University education 6,634 (17.3) 257,727 (22.5) Missing 810 (2.1) 17,598 (1.5) Charlson Comorbidity Index, No. (%) 0 12,523 (32.7) 529,312 (46.2) 1–2 16,019 (41.9) 416,326 (36.3) 3–5 8,195 (21.4) 163,716 (14.3) 6+ 1,515 (4.0) 36,760 (3.2) Cerebrovascular.disease 9,977 (26.1) 146,723 (12.8) Diabetes with complications 2,265 (5.9) 44,659 (3.9) Diabetes without complications 3,059 (8.0) 61,043 (5.3) Myocardial.infarction 2,914 (7.6) 70,506 (6.2) AIDS/HIV < 20 (< 0.1) 828 (0.1) Chronic pulmonary disease 5,239 (13.7) 131,610 (11.5) Heart failure 3,299 (8.6) 67,569 (5.9) Hemiplegia/paraplegia 187 (0.5) 4,968 (0.4) Mild liver disease 637 (1.7) 17,463 (1.5) Peptic ulcer disease 2,744 (7.2) 49,391 (4.3) Peripheral vascular disease 3,276 (8.6) 77,029 (6.7) Renal disease 1,612 (4.2) 30,825 (2.7) Rheumatic disease 2,437 (6.4) 61,786 (5.4) Severe liver disease 164 (0.4) 4,639 (0.4) Any malignancy 8,620 (22.5) 221,791 (19.4) Metastatic solid tumor 436 (1.1) 17,445 (1.5) Leukemia 183 (0.5) 6,511 (0.6) Lymphoma 458 (1.2) 14,718 (1.3) Psychiatric comorbidity, No. (%) 7,958 (20.8) 107,515 (9.4) Psychotic disorders 1,131 (3.0) 14,638 (1.3) Mood disorders 5,696 (14.9) 58,054 (5.1) Anxiety disorders 3,572 (9.3) 65,548 (5.7) Open in a new tab The prevalence proportion of polypharmacy in the first quarter of 2022 was 56.2% among people with dementia and 35.6% among people without dementia (Table 2 ). After age- and sex-standardization, the prevalence of polypharmacy in individuals with dementia was 51.6%. For CNS-polypharmacy, the prevalences were 10.1% (standardized 10%) and 2.3% respectively for individuals with and without dementia. The fully adjusted OR (95% CI) of polypharmacy among people with dementia was 1.47 (1.44–1.51) compared to people without dementia while the OR was 2.70 (2.59–2.81) for CNS-polypharmacy (Table 2 ). Detailed characteristics of the study population according to polypharmacy status are displayed in Supplementary Table S2. Table 2. Period prevalence proportion and odds ratios (OR) of polypharmacy in individuals with dementia compared to individuals without dementia Dementia status Prevalence % Age/sex-standardized e prevalence % (95% CI) Crude OR (95% CI) Adjusted OR c (95% CI) Adjusted OR d (95% CI) Polypharmacy a Dementia 56.2 51.6 (50.7–52.5) 2.32 (2.27–2.37) 1.62 (1.59–1.66) 1.47 (1.44–1.51) No dementia 35.6 35.9 (35.8–36.0) 1 1 1 CNS-active polypharmacy b Dementia 10.1 10.1 (9.5–10.7) 4.75 (4.58–4.92) 3.80 (3.66–3.94) 2.70 (2.59–2.81) No dementia 2.3 2.3 (2.3–2.3) 1 1 1 Open in a new tab a Concurrent use of ≥ 5 drugs b Concurrent use of ≥ 3 CNS-active drugs c Adjusted for age, sex, and educational level d Additionally adjusted for CCI score and psychiatric disorders e Standardized to the age and sex distribution of older adults without dementia in 2022 Table 3 ranks the most frequently used pharmacological subgroups and the most frequently used generic drug within each respective subgroup among individuals with dementia and polypharmacy/CNS-active polypharmacy. The most used drug groups particularly included drugs used in the treatment and prevention of cardiovascular disease. The most used CNS-active drug groups included antidepressants, opioids, and antipsychotics. Corresponding user proportions within the 3-month observation window are provided in Supplementary table S8. Table 3. Most frequently used Pharmacological subgroups and products among individuals with dementia and polypharmacy Rank ATC 3rd level Pharmacological subgroup Most frequent generic drug Most used drug groups/drugs in people with dementia and polypharmacy 1 N02B Other analgesics and antipyterics Paracetamol 2 B01A Antithrombotic agents Acetylsalicylic acid 3 N06A Antidepressants Sertraline 4 A06A Drugs for constipation Macrogol 5 C10A Lipid modifying agents Atorvastatin 6 J01C Penicillins Pivmecillinam 7 N02A Opioids Tramadol 8 A02B Drugs for acid related disorders Pantoprazole 9 C07A Beta blocking agents Metoprolol 10 A12B Potassium Potassium chloride 11 C08C Selective calcium channel blockers Amlodipine 12 C03C High-ceiling diuretics Furosemide 13 A10B Glucose lowering drugs, excl. insulins Metformin 14 N05A Antipsychotics Quetiapine 15 N05C Hypnotics and sedatives Zopiclone 16 C09C Angiotensin II receptor blockers Losartan 17 R03A Adrenergics, inhalants Terbutaline 18 N04B Dopaminergic agents Pramipexole 19 C09A ACE inhibitors Enalapril 20 B03B Vitamin B12 and folic acid Vitamin B12 Most used CNS-active drug groups/drugs in people with dementia and CNS-active polypharmacy 1 N06A Antidepressants Sertraline 2 N02A Opioids Tramadol 3 N05A Antipsychotics Quetiapine 4 N05C Hypnotics and sedatives Zopiclone 5 N03A Antiepileptics Lamotrigine 6 N05B Anxiolytics Oxazepam 7 N07B Drugs used in addictive disorders Buprenorphine Open in a new tab Figure 1 demonstrates polypharmacy time trends according to dementia status. The prevalence of polypharmacy among people with dementia declined by 8.9% points (14% relative reduction) between 2012 and 2022 from 65.1% (standardized 59.3%) to 56.2% (standardized 51.6%) while it remained stable for people without dementia at around 35–36%. CNS-active polypharmacy declined by 5.0% points from 15.0% to 10.0% in people with dementia and by 1.2% points from 3.5% to 2.3% in people without dementia (33% and 34% relative reductions, respectively) (Fig. 2 ). Exact values for time trends are shown in Supplementary Tables S3-S4. Fig. 1. Open in a new tab Time trends of the crude and age-/sex-standardized a prevalence of polypharmacy according to dementia status. a Standardized to the age and sex distribution of older adults without dementia in the corresponding year Fig. 2. Open in a new tab Time trends of the crude and age-/sex-standardized a prevalence of CNS-active polypharmacy according to dementia status. a Standardized to the age and sex distribution of older adults without dementia in the corresponding year. For community-dwelling individuals, the prevalence of polypharmacy was higher among people with dementia compared to people without dementia (50.0% versus 34.8%, adjusted OR 1.24 (1.20–1.27)) (Supplementary Table S5). In contrast, for individuals living in nursing home, polypharmacy was less frequent among people with dementia compared to people without dementia (64.8% versus 73.8%, adjusted OR 0.74 (0.71–0.78)). The corresponding prevalences for CNS-active polypharmacy were 6.1% versus 2.0% for community-dwelling individuals and 15.5% versus 14.8% for nursing home residents. Polypharmacy prevalences increased among people with and without dementia when defined from prescriptions within the first six months of 2022 instead of the first three months (Supplementary Table S6). Nonetheless, both crude and adjusted ORs of polypharmacy and CNS-active polypharmacy remained largely unchanged compared with the main results. Switching ATC level 5 with level 4 in the definition of polypharmacy did not change the results (Supplementary Table S7). Discussion Principal findings In this nationwide Danish study, 56% of people with dementia had polypharmacy and 10% had CNS-active polypharmacy in 2022 (36% and 2% for people without dementia). The prevalence declined from 65% in 2012 for polypharmacy, and from 15% for CNS-active polypharmacy. Despite this trend, the odds of experiencing polypharmacy were 1.47-fold higher for people with dementia than those without, and 2.7-fold higher in CNS-active polypharmacy even after adjustment for sociodemographic and health-related covariates. Comparison with previous studies Our findings align with a previous Danish study documenting declining use of potentially inappropriate medication in people with dementia from 2000 to 2015 [ 9 ]. Comparable to our observations, the authors still reported a widespread use of polypharmacy in the older population with a markedly higher prevalence in people with dementia [ 10 ]. Our findings further align with studies reporting extensive use of polypharmacy in individuals with dementia in the US driven by diverse medication classes [ 28 ]. This study confirms a nationwide decades-long decline in polypharmacy while documenting persistent disparities in medication load among individuals with and without dementia. A recent meta-analysis pooling 28 studies reported a global prevalence of polypharmacy of 62% (95% CI 52–71) among older individuals with dementia, although there was substantial heterogeneity across regions and care settings [ 29 ]. Cross-national analyses of Israel and 24 European Union countries (2015–2019) showed that polypharmacy among people living with dementia ranged from about 20% in Estonia to 85% in Cyprus, with increasing trends in Switzerland, Poland, Austria, and the Czech Republic and decreasing trends in Spain, Estonia, Denmark, Bulgaria, and the Netherlands [ 30 ]. Despite differences in study populations, periods, and definitions, the evidence consistently indicates a high prevalence of polypharmacy among people with dementia. Our finding of markedly higher prevalence and odds ratio of CNS-active polypharmacy among people with dementia compared to people without dementia is in line with a recent study based on US data. In that study, 14% of older adults with dementia experienced CNS-active polypharmacy in 2018, particularly with high exposure to antidepressants, antipsychotics, and opioids similar to our Danish findings [ 25 ]. In addition, recent findings demonstrate that psychotropic polypharmacy is highly prevalent among Australians with dementia, particularly involving the use of antipsychotics and opioids [ 31 ]. This reliance on psychotropic medications across healthcare systems underscores the urgent need for safer prescribing practices to mitigate potential risks, including cognitive impairment and adverse health outcomes [ 2 , 32 ]. Our finding of persistently elevated CNS-active polypharmacy after adjustment may reflect unrecorded neuropsychiatric symptoms, reduced deprescribing in dementia, or potential contribution to cognitive decline, leading to earlier recognition of dementia. While the prevalence of polypharmacy remained relatively low and stable for people without dementia throughout the last decade, there was a declining trend among people with dementia. Several factors may have influenced this seemingly positive development. Both national [ 15 , 16 ] and international guidelines and initiatives with particular focus on dementia have heightened awareness of medication risks, prompting clinicians to conduct more frequent and systematic medication reviews [ 14 ]. For instance, in 2018, the Danish Health Authority published a national clinical guideline on dementia and medicine [ 16 ]. Additionally, non-pharmacological interventions for behavioral and psychological symptoms of dementia have been recommended and emphasized during the study period [ 11 , 12 ]. Updated prescribing tools (e.g., the updated Beers Criteria) may also have influenced deprescribing efforts. In addition, published evidence and its dissemination have drawn attention to potential prescribing issues and supported the development of initiatives aimed at safer medication use in dementia care [ 25 , 33 ] . The indication or appropriateness of drug use was not considered, thus, the presence of polypharmacy itself did not distinguish between potentially appropriate or inappropriate medications. Thus, higher polypharmacy prevalence in dementia may partly reflect multimorbidity rather than inappropriate prescribing. For instance, as reflected by the list of most used drug classes, individuals with dementia frequently use antihypertensives, antithrombotic agents, lipid modifying agents, and antidepressants likely due to higher prevalence of the conditions treated [ 34 ]. In contrast to community-dwelling individuals, we observed a lower prevalence and odds of polypharmacy among dementia residents in nursing homes than residents without dementia corroborating similar findings from a previous Danish study on the topic [ 10 ]. This relatively lower occurrence of polypharmacy in nursing home residents with dementia is likely influenced by that fact that residents in nursing homes without dementia are likely there for health-related reasons (requiring medication) different than those with dementia, whose presence is largely driven by cognitive and functional decline. Second, the difference might also be due to specific nursing home initiatives such as nursing home physicians and prioritization of nonpharmacological interventions for behavioral disturbances [ 11 – 13 , 34 – 37 ]. Regular medication audits and staff education may have further reduced medication load in this setting. Another possibility is that patients with advanced dementia may discontinue certain preventive therapies, contributing to a lower total count of prescribed medications. Finally, the proportionally higher polypharmacy among nursing home residents without recorded dementia may reflect undiagnosed dementia with higher prevalence of neuropsychiatric symptoms as well as more cautious prescribing for residents with confirmed dementia. Overall, nursing homes might serve as relevant settings for investigating and improving safe prescribing strategies. Despite improvements, the high prevalence of polypharmacy in dementia reflects not only the clinical challenges posed by multimorbidity and neuropsychiatric symptoms, but also necessitates targeted interventions and further research. Future studies should investigate specific drugs/drug classes contributing to medication burden, the clinical appropriateness of polypharmacy, and the impact of deprescribing efforts in real-world settings. Furthermore, the development of dementia-specific treatment guidelines incorporating both pharmacological and nonpharmacological management is critical [ 11 , 12 , 16 ]. Strengths and limitations The national Danish registers enable highly valid assessment of prescription patterns and diagnoses at the individual level of a nationwide population minimizing both selection and information bias. This study has limitations. First, while polypharmacy was based on filled prescriptions in accordance with previous literature [ 1 , 24 , 25 ], we could not ensure that the medication was consumed. Information on drugs bought over the counter was not available, thus, leading to an underestimation of drug use. Second, while dementia syndrome diagnoses in Danish hospital registers have a high positive predictive value, dementia is expectedly underdiagnosed in the population as a whole potentially leading to misclassification. E.g., in nursing homes, a substantial proportion of residents are likely to have dementia or cognitive impairment, even in the absence of a formal diagnosis or treatment. Third, residual bias cannot be ruled out in the adjusted analyses. Because drug use is inherently linked to underlying health conditions, and comorbidities differ between people with and without dementia, the adjusted models should be interpreted as descriptive associations. Our regression analyses were intended to characterize differences in polypharmacy patterns after accounting for measured covariates. In conclusion, both polypharmacy and CNS-active polypharmacy declined among individuals with dementia between 2012 and 2022 suggesting growing awareness of the associated risks. Nonetheless, the prevalence of polypharmacy remains substantially higher in dementia. The findings highlight the continued need for safer prescribing practices taking morbidities and associated medication risks into account. Supplementary Information Supplementary Material 1. (93.7KB, docx) Abbreviations ATC Anatomical therapeutic chemical classification system CCI Charlson comorbidity index CI Confidence interval CNS Central nervous system ICD International classification of diseases IQR Interquartile range OR Odds ratio Authors’ contributions The study was initiated by NP, GW, CJD, and JJ. All authors contributed to the study design and methods. NP, JJ, CJD, GW, and TML had access to the data. Data was verified by NP and JJ, and analyses were conducted by NP. All authors contributed to interpretation. NP drafted the manuscript, and all authors contributed to review and editing. All authors had access to analyzed data, approved the final version of the manuscript, and agreed with submission for publication. Funding Open access funding provided by Copenhagen University. The Research Fund of Rigshospitalet, Copenhagen University Hospital funded this study (E-22100-04). Danish Dementia Research Centre is supported by the Danish Ministry of Health (No. 1604063). Funders were not involved in the study design, analysis, data interpretation, or writing the manuscript. Data availability This study was based on raw data derived from the national Danish registers only available with approval from the Danish Health Data Board and the Danish Data Protection Agency. Since the data was accessible on individual level, data sharing is restricted by the General Data Protection Regulation (GDPR) of European Union (EU) law. The protocol and program code for the study can be accessed upon request from the corresponding author. Declarations Ethics approval and consent to participate This study used pseudo-anonymized data from national Danish registers, authorized by the Danish Data Protection Agency and the Danish Health Data Authority. According to Danish law, register-based studies do not require ethics committee approval or patient consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Footnotes Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol. 2012;65:989–95. 10.1016/j.jclinepi.2012.02.018. [ DOI ] [ PubMed ] [ Google Scholar ] 2. Mueller C, Molokhia M, Perera G, Veronese N, Stubbs B, Shetty H, et al. Polypharmacy in people with dementia: associations with adverse health outcomes. Exp Gerontol. 2018;106:240–5. 10.1016/j.exger.2018.02.011. [ DOI ] [ PubMed ] [ Google Scholar ] 3. Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, et al. Reducing inappropriate polypharmacy. JAMA Intern Med. 2015;175:827. 10.1001/jamainternmed.2015.0324. [ DOI ] [ PubMed ] [ Google Scholar ] 4. Pfister B, Jonsson J, Gustafsson M. Drug-related problems and medication reviews among old people with dementia. BMC Pharmacol Toxicol. 2017;18:52. 10.1186/s40360-017-0157-2. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 5. Clague F, Mercer SW, McLean G, Reynish E, Guthrie B. Comorbidity and polypharmacy in people with dementia: insights from a large, population-based cross-sectional analysis of primary care data. Age Ageing. 2016. 10.1093/ageing/afw176. [ DOI ] [ PubMed ] [ Google Scholar ] 6. Parsons C. Polypharmacy and inappropriate medication use in patients with dementia: an underresearched problem. Ther Adv Drug Saf. 2017;8:31–46. 10.1177/2042098616670798. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 7. Gnjidic D, Hilmer SN, Hartikainen S, Tolppanen A-M, Taipale H, Koponen M et al. Impact of High Risk Drug Use on Hospitalization and Mortality in Older People with and without Alzheimer’s Disease: A National Population Cohort Study. Sleegers K, editor. PLoS One. 2014;9:e83224. 10.1371/journal.pone.0083224 [ DOI ] [ PMC free article ] [ PubMed ] 8. Bayliss EA, Shetterly SM, Drace ML, Norton J, Green AR, Reeve E, et al. The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial. Trials. 2020;21:542. 10.1186/s13063-020-04482-0. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 9. Kristensen RU, Jensen-Dahm C, Gasse C, Waldemar G. Declining use of potentially inappropriate medication in people with dementia from 2000 to 2015: A repeated Cross-Sectional nationwide Register-Based study. J Alzheimer’s Disease. 2021;79:1459–70. 10.3233/JAD-200627. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 10. Kristensen RU, Nørgaard A, Jensen-Dahm C, Gasse C, Wimberley T, Waldemar G. Polypharmacy and Potentially Inappropriate Medication in People with Dementia: A Nationwide Study. Tan E, editor. Journal of Alzheimer’s Disease. 2018;63:383–94. 10.3233/JAD-170905 [ DOI ] [ PubMed ] 11. Scales K, Zimmerman S, Miller SJ. Evidence-Based nonpharmacological practices to address behavioral and psychological symptoms of dementia. Gerontologist. 2018;58:S88–102. 10.1093/geront/gnx167. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 12. Austrom MG, Boustani M, LaMantia MA. Ongoing medical management to maximize health and Well-being for persons living with dementia. Gerontologist. 2018;58:S48–57. 10.1093/geront/gnx147. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 13. Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing medications for chronic diseases management in primary care settings: A systematic review of randomized controlled trials. J Am Med Dir Assoc. 2018;19:923–e9352. 10.1016/j.jamda.2018.06.021. [ DOI ] [ PubMed ] [ Google Scholar ] 14. American Geriatrics Society. 2019 updated AGS beers Criteria ® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67:674–94. 10.1111/jgs.15767. [ DOI ] [ PubMed ] [ Google Scholar ] 15. Sundhedsstyrelsen Danish Health Authority. Evidensgennemgang for anbefalinger om polyfarmaci ved multisygdom. 2022. https://www.sst.dk 16. Sundhedsstyrelsen Danish Health Authority. National clinical guideline on dementia and medicine. https://www.sst.dk/-/media/Udgivelser/2018/NKR-medicin-og-demens/EN/Quick-Guide-NKR-demens-og-medicin_EN.ashx 17. Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National patient registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;449. 10.2147/CLEP.S91125. [ DOI ] [ PMC free article ] [ PubMed ] 18. Mors O, Perto GP, Mortensen PB. The Danish psychiatric central research register. Scand J Public Health. 2011;39:54–7. 10.1177/1403494810395825. [ DOI ] [ PubMed ] [ Google Scholar ] 19. Schmidt M, Hallas J, Laursen M, Friis S. Data resource profile: Danish online drug use statistics (MEDSTAT). Int J Epidemiol. 2016;45:1401–g1402. 10.1093/ije/dyw116. [ DOI ] [ PubMed ] [ Google Scholar ] 20. Jensen VM, Rasmussen AW. Danish education registers. Scand J Public Health. 2011;39:91–4. 10.1177/1403494810394715. [ DOI ] [ PubMed ] [ Google Scholar ] 21. Kristensen GS, Wolff DL, Søndergaard J, Andersen-Ranberg K, Mogensen CB. Exploring the validity of identifying care home residents through a new National register. Scand J Public Health. 2023;51:911–7. 10.1177/14034948221081071. [ DOI ] [ PubMed ] [ Google Scholar ] 22. Pedersen CB. The Danish civil registration system. Scand J Public Health. 2011;39:22–5. 10.1177/1403494810387965. [ DOI ] [ PubMed ] [ Google Scholar ] 23. Phung TKT, Andersen BB, Høgh P, Kessing LV, Mortensen PB, Waldemar G. Validity of dementia diagnoses in the Danish hospital registers. Dement Geriatr Cogn Disord. 2007;24:220–8. 10.1159/000107084. [ DOI ] [ PubMed ] [ Google Scholar ] 24. Bjerrum L, Rosholm JU, Hallas J, Kragstrup J. Methods for estimating the occurrence of polypharmacy by means of a prescription database. Eur J Clin Pharmacol. 1997;53:7–11. 10.1007/s002280050329. [ DOI ] [ PubMed ] [ Google Scholar ] 25. Maust DT, Strominger J, Kim HM, Langa KM, Bynum JPW, Chang C-H, et al. Prevalence of central nervous System–Active polypharmacy among older adults with dementia in the US. JAMA. 2021;325:952. 10.1001/jama.2021.1195. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 26. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis [Internet]. 1987;40:373–83. 10.1016/0021-9681(87)90171-8. [ DOI ] [ PubMed ] [ Google Scholar ] 27. R Core Team. (2020) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org 28. Growdon ME, Gan S, Yaffe K, Steinman MA. Polypharmacy among older adults with dementia compared with those without dementia in the < scp>United States. J Am Geriatr Soc. 2021;69:2464–75. 10.1111/jgs.17291. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 29. Zhao M, Chen Z, Xu T, Fan P, Tian F. Global prevalence of polypharmacy and potentially inappropriate medication in older patients with dementia: a systematic review and meta-analysis. Front Pharmacol. 2023;14. 10.3389/fphar.2023.1221069. [ DOI ] [ PMC free article ] [ PubMed ] 30. Chen S, Chen X, Zhang H. Polypharmacy among people living with Dementia — Israel and 24 countries in European Union, 2015–2019. China CDC Wkly. 2022;4:1007–12. 10.46234/ccdcw2022.204. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 31. Atee M, Stafford A, Whiting D, Lee YP, Morrow C, Nyakaboyi G, et al. Psychotropic polypharmacy in dementia: A retrospective analysis for people with neuropsychiatric symptoms referred to an Australian dementia support service. Drugs Aging. 2025. 10.1007/s40266-024-01177-y. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 32. Borda MG, Castellanos-Perilla N, Tovar-Rios DA, Oesterhus R, Soennesyn H, Aarsland D. Polypharmacy is associated with functional decline in alzheimer’s disease and lewy body dementia. Arch Gerontol Geriatr. 2021;96:104459. 10.1016/j.archger.2021.104459. [ DOI ] [ PubMed ] [ Google Scholar ] 33. Nørgaard A, Jensen-Dahm C, Gasse C, Hansen ES, Waldemar G. Psychotropic Polypharmacy in Patients with Dementia: Prevalence and Predictors. Fischer C, editor. Journal of Alzheimer’s Disease. 2017;56:707–16. 10.3233/JAD-160828 [ DOI ] [ PubMed ] 34. Perron AE. Towards a prescription for change: interprofessional management of polypharmacy and deprescribing. Curr Geriatr Rep. 2024;13:152–61. 10.1007/s13670-024-00420-z. [ Google Scholar ] 35. Hung A, Kim YH, Pavon JM. Deprescribing in older adults with polypharmacy. BMJ. 2024. 10.1136/bmj-2023-074892. e074892. [ DOI ] [ PubMed ] [ Google Scholar ] 36. Tkatch R, Hudson J, Schaeffer J, Yeh CS. Non-Pharmacologic approaches to reducing polypharmacy in older adults. Public Policy Aging Rep [Internet]. 2018;28:140–2. 10.1093/ppar/pry039. [ Google Scholar ] 37. Parajuli DR, Kuot A, Hamiduzzaman M, Gladman J, Isaac V. Person-centered, non-pharmacological intervention in reducing psychotropic medications use among residents with dementia in Australian rural aged care homes. BMC Psychiatry. 2021;21:36. 10.1186/s12888-020-03033-w. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Supplementary Material 1. (93.7KB, docx) Data Availability Statement This study was based on raw data derived from the national Danish registers only available with approval from the Danish Health Data Board and the Danish Data Protection Agency. Since the data was accessible on individual level, data sharing is restricted by the General Data Protection Regulation (GDPR) of European Union (EU) law. The protocol and program code for the study can be accessed upon request from the corresponding author. Articles from Alzheimer's Research & Therapy are provided here courtesy of BMC ACTIONS View on publisher site PDF (1.0 MB) Cite Collections Permalink PERMALINK Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Add to Collections Create a new collection Add to an existing collection Name your collection * Choose a collection Unable to load your collection due to an error Please try again Add Cancel Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top