---
title: "Pre-diagnostic 1-year prevalence of polypharmacy and PIMcog in Norwegian outpatients with MCI or d"
id: "plos-one-14-one-year-pre-diagnostic-prevalence-and-associated-factors-of-polypharmacy-and"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-14-one-year-pre-diagnostic-prevalence-and-associated-factors-of-polypharmacy-and"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356275"
published_at: "2026-08-18T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Pre-diagnostic 1-year prevalence of polypharmacy and PIMcog in Norwegian outpatients with MCI or d
## Provenance & Clinical Metadata
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- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356275)
- **Published At:** 2026-08-18T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This registered report protocol describes a retrospective registry-based cohort study using Norwegian national data sources to estimate the 12-month pre-diagnostic prevalence of **polypharmacy** and **potentially inappropriate medications for cognitive impairment (PIMcog)** among community-dwelling adults assessed in specialist outpatient clinics for cognitive symptoms between 2014 and 2024. - The study will link the Norwegian Registry of Persons Assessed for Cognitive Symptoms (**NorCog**) with dispensing data from the Norwegian Prescribed Drug Registry (**NorPD**) and comorbidity data from the Norwegian Patient Registry (NPR) using personal identifiers. - The population comprises all patients diagnosed with mild cognitive impairment (MCI) or dementia in NorCog during 2014–2024; NorCog includes data from 46 clinics and about 27,500 patients (mean age ≈74) with ~85% diagnosed with MCI or dementia. - Primary outcomes are the twelve-month prevalence of polypharmacy and PIMcog use prior to diagnosis. The protocol will compare sociodemographic and clinical characteristics between PIMcog users and non-users and model factors associated with PIMcog use, including comorbidity burden. - Rationale: older adults with cognitive impairment frequently have multiple comorbidities and higher medication counts; prior studies report ~50% polypharmacy in dementia and variable PIMcog prevalence (20–82% in different settings), but no Nordic specialist outpatient prevalence estimates exist. - PIMcog are defined according to established tools (STOPP, Beers) and include CNS depressants, benzodiazepines, certain antipsychotics, and drugs with strong anticholinergic effects that may worsen cognition or increase adverse drug events. - NorPD provides individual-level dispensing records, enabling precise measurement of medication exposure in the year before diagnosis; NPR contributes comorbidity information, and linkage is subject to legal and ethical restrictions on data sharing. - Expected impact: findings aim to inform targeted deprescribing interventions, safer prescribing strategies, and improved medication safety for individuals with cognitive impairment. Study materials will be shared on OSF; individual-level data access requires application to data custodians and approvals. - Funding: part of a PhD project funded by Foundation Dam via the Norwegian Health Association. The authors declare no competing interests.
## Clinical Analysis & Structured Key Points
One year pre-diagnostic prevalence and associated factors of polypharmacy and potentially inappropriate medication use in community-dwelling adults with mild cognitive impairment or dementia in Norway (2014–2024): A registered report protocol | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Background People with cognitive impairment frequently have multiple comorbidities, and polypharmacy is highly prevalent, affecting nearly half of individuals with mild cognitive impairment and dementia. The use of potentially inappropriate medications (PIMs), including those specifically problematic for cognitive impairment (PIMcog), increases with the total number of medications and may exacerbate cognitive symptoms or increase the risk of adverse drug events. However, the prevalence of polypharmacy and PIMcog use among patients diagnosed with MCI or dementia in Norwegian specialist outpatient clinics has not been described. Methods We will conduct a retrospective cohort study linking national health registries to estimate the prevalence of polypharmacy and PIMcog use in the year prior to diagnosis of mild cognitive impairment or dementia. Data from the Norwegian Registry of Persons Assessed for Cognitive Symptoms will be linked to dispensing data from the Norwegian Prescribed Drug Registry and comorbidity data from the Norwegian Patient Registry. The study population will include all patients diagnosed with mild cognitive impairment or dementia in Norwegian specialist outpatient clinics from 2014 to 2024. We will estimate the twelve-month prevalence of polypharmacy and PIMcog use preceding diagnosis, compare sociodemographic and clinical characteristics between PIMcog users and non-users, and identify factors associated with PIMcog use. Expected impact By describing the one-year prevalence and patterns of polypharmacy and PIMcog use and associated factors prior to mild cognitive impairment and dementia diagnosis, the findings may inform targeted deprescribing interventions and safer prescribing strategies for individuals with cognitive impairment. Citation: Kersten H, Vaksvik TMB, Romskaug R, Bruun Wyller T, Jaioun K, Botteri E, et al. (2026) One year pre-diagnostic prevalence and associated factors of polypharmacy and potentially inappropriate medication use in community-dwelling adults with mild cognitive impairment or dementia in Norway (2014–2024): A registered report protocol. PLoS One 21(8): e0356275. https://doi.org/10.1371/journal.pone.0356275 Editor: Mohammed Mustapha, Qatar University, QATAR Received: January 23, 2026; Accepted: July 31, 2026; Published: August 18, 2026 Copyright: © 2026 Kersten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The study uses data from Norwegian national health registries (NorCog, NorPD, NPR). Due to legal and ethical restrictions, individual-level data cannot be made publicly available, as public deposition would breach the conditions of approval by ethics committees and data protection regulations. Qualified researchers may apply for access through the relevant data custodians, including NorPD, NPR, and the NorCog Expert Council, subject to ethical and regulatory approvals. Study materials and supporting documentation will be made available via the Open Science Framework (OSF). Funding: This is part of a PhD project funded by Foundation Dam ( https://www.dam.no) through the Norwegian Health Association ( https://nasjonalforeningen.no) . HK received the funding. (SDAM_FOR701628) The Norwegian Health Association accepted the application to the Foundation Dam. Foundation Dam requires two-steps publication with RR Protocol and then RR report. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Abbreviations: BPSD, Behavioral and psychological symptoms of dementia; CCI, Charlson Comorbidity Index; CSDD, Cornell Scale for Depression in Dementia; CFS, Clinical Frailty Scale; MCI, Mild cognitive impairment; NPI-Q, Neuropsychiatric Inventory Questionnaire; NorCog, Norwegian Registry of Persons Assessed for Cognitive Symptoms; NorPD, Norwegian Prescribed Drug Registry; NPR, Norwegian Patient Registry; PIM, Potentially inappropriate medication; PIMcog, Potentially inappropriate medication for cognitive impairment Introduction The risk of developing dementia and mild cognitive impairment (MCI) increases markedly with age. By 2050, one-fifth of Norway’s population of 6.2 million will be aged ≥70 years [ 1 ]. In 2025, the prevalence of dementia in Norway is estimated at 115,000, and this number is expected to more than double to 237,000 by 2050 [ 2 ]. As the prevalence of dementia rises, there is increasingly focus on identifying modifiable risk factors that may be targeted to delay disease onset and mitigate the symptom burden [ 3 ]. The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established as a national quality registry in 2013. The purpose of NorCog is to harmonize and improve the diagnostic work-up across specialized healthcare units assessing persons with cognitive symptoms [ 4 ]. In 2024, there were 46 clinics providing data to the registry. In total, 27,500 patients are included in the register, with a mean age of about 74 years. Almost 85% of these patients have been diagnosed with MCI or dementia. NorCog constitutes a large research cohort with extensive diagnostic and treatment data and has contributed to 74 published studies [ 5 ]. Multiple comorbid conditions develop with aging, and the prevalence of comorbid medical illnesses in individuals with dementia increases with dementia severity [ 6 ]. Older adults with dementia have more than twice the burden of physical comorbid conditions compared to age- and sex-matched controls without dementia [ 7 ]. Common coexisting conditions in dementia include depression, diabetes, coronary heart disease, stroke, hypertension, heart failure, and incontinence [ 7 – 9 ]. These conditions are typically managed with multiple medications. In addition, pharmacological treatment is often used to manage cognitive symptoms and behavioral and psychological symptoms of dementia (BPSD) [ 10 , 11 ]. Consequently, around 50% of individuals with dementia are exposed to polypharmacy, and their average medication use is higher than that of individuals without dementia [ 6 , 12 ]. In a population-based study from Norway, including 187 community-dwelling patients with Alzheimer’s dementia and 200 controls, the age- and sex-adjusted mean number of medications was 5.1 ± 3.6 among individuals with Alzheimer’s dementia compared to 2.9 ± 2.4 among cognitively healthy controls [ 13 ]. According to the Screening Tool of Older Persons’ Prescriptions (STOPP) and the Beers criteria, widely used prescription tools in geriatric medicine, CNS-depressants such as benzodiazepines (BZDs), BZD-related drugs, certain antipsychotics, and drugs with strong anticholinergic effects are considered potentially inappropriate medications for individuals with cognitive disorders (PIMcog) [ 14 , 15 ]. This inappropriateness is due to drug–disease interactions, which can exacerbate cognitive decline and functional impairment [ 16 – 19 ]. Despite their risks, PIMcog are still commonly prescribed for managing BPSD. In the United States, 82% of patients referred to a hospital for evaluation of cognitive decline used sedatives or anticholinergic drugs [ 18 ]. Other studies have shown a 20–30% prevalence of PIMcog in community-dwelling older adults with cognitive disorders [ 16 , 20 ]. A systematic review, including 11 studies from memory clinics in eight different countries, found PIM- and polypharmacy rates of 38% and 60%, respectively, with significant variation between countries. No prevalence studies from the Nordic countries were included in the review [ 21 ]. Prescription patterns and PIMcog prevalence vary with local pharmacotherapeutic practices, highlighting the need for studies in Nordic specialist outpatient clinics. No such prevalence studies have previously been conducted in Norway, but trends of psychotropic drug use in nursing homes and among community-dwelling individuals with dementia have shown a decrease in antipsychotic drug use in the last decades, but only minor changes for the other psychotropic drugs [ 22 , 23 ]. The Norwegian Prescribed Drug Registry (NorPD) contains detailed information on all prescriptions dispensed at Norwegian pharmacies, recorded at the individual level using unique national personal identifying number. This enables linkage to other national health registries [ 24 ]. In this registry based study, we link NorCog data with NorPD to estimate the twelve-month prevalence of polypharmacy and PIMcog use prior to diagnosis of MCI or dementia in Norwegian outpatient clinics. In addition, we will incorporate information on comorbidities to identify clinical characteristics associated with PIMcog use. The findings may inform targeted screening and deprescribing strategies, improve medication safety, and support optimization of pharmacological treatment in this vulnerable population [ 21 ]. The present study This study aims to estimate the 12-month prevalence of polypharmacy and potentially inappropriate cognitive-impairing medications in the year preceding a diagnosis of MCI and dementia in Norwegian specialist outpatient clinics. By characterizing prescribing patterns and identifying patient characteristics associated with PIMcog use, the study seeks to inform targeted deprescribing strategies and improve the quality of pharmacological care. Ultimately, the goal is to reduce drug-related cognitive decline and preserve functional autonomy and quality of life in individuals living with MCI and dementia. Objectives and hypotheses The objectives of the present study are to: 1] Estimate the 12-month prevalence of polypharmacy (≥5 concurrent medications) and PIMcog - including benzodiazepines, benzodiazepine derivatives, benzodiazepine-related drugs, anticholinergics and antipsychotics- among community-dwelling individuals in the year prior to a diagnosis of MCI or dementia in Norwegian outpatient clinics during the period 2014–2024. 2] Compare the characteristics of PIMcog users and non-users, and identify factors associated with PIMcog use among community-dwelling individuals diagnosed with MCI or dementia who are registered in NorCog from 2014 to 2024. We hypothesize that: 1). The prevalence of polypharmacy has increased over the study period, while PIMcog prescribing patterns have changed and vary across regions. 2). PIMcog use is associated with greater disease burden, including more severe dementia, higher comorbidity, older age, higher overall medication use, and a higher prevalence of BPSD. Materials and methods Design and setting This is a registry based retrospective cohort study linking data from NorCog, NorPD, and the Norwegian Patient Registry (NPR). The primary outcomes of the study are the 12-month prevalence of polypharmacy and PIMcog use among community-dwelling individuals diagnosed with MCI or dementia in Norwegian specialist outpatient clinics during the study period from 2014 to 2024. In addition, the study will identify factors associated with PIMcog use and characterize temporal trends and regional variation in prescribing patterns over the study period. Data collection Selection of the study population registered in NorCog. NorCog collects data according to a standardized assessment manual in hospital outpatient clinics in Norway, with the aim of harmonizing and improving the diagnostic work-up for individuals referred for assessment of cognitive symptoms and suspected dementia [ 4 ]. Patients are encouraged to bring a family member or another close informant with regular contact and sufficient knowledge of the patient’s cognitive and functional status. NorCog was established in 2008 with seven participating outpatient clinics, expanding to 46 outpatient clinics by the end of 2024. NorCog became a national medical quality registry in 2013 and reported a coverage ratio of 70% for individuals diagnosed with dementia in specialized healthcare units in Norway in 2024 [ 5 ]. Participation in NorCog was voluntary during the study period and required informed consent. Until the end of 2021, only patients with the capacity to provide written informed consent were eligible for inclusion. Since January 2022, patients lacking capacity to provide written informed consent could be included based on proxy consent. According to the American Geriatrics Society Beers Criteria® and STOPP version 3, both prescribing tools intended for individuals aged ≥65 years, PIMcog should be avoided in those with cognitive impairment. In this study, we will identify PIMcog among community-dwelling patients referred to specialist outpatient clinics who are diagnosed with MCI or dementia and registered in NorCog 01/01/2014 to 12/31/2024. As NorPD does not record information on medications dispensed in institutional care, only community-dwelling patients are eligible for inclusion in this study. Diagnoses are assigned following comprehensive clinical assessments in outpatient clinics specialized in the assessment and diagnosis of cognitive impairment and dementia. The assessments include medical history, cognitive testing, evaluation of functional status, clinical examination, and information from informants. When relevant, neuroimaging and laboratory investigations are also performed. Diagnostic classification is based on established criteria, with MCI defined according to the Winblad criteria and dementia diagnosed according to ICD-10 [ 25 , 26 ]. Where possible, further etiological subtyping is performed using recognized research criteria, including the National Institute on Ageing–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease criteria for Alzheimer’s disease, VASCOG criteria for vascular dementia, McKeith criteria for dementia with Lewy bodies, Emre criteria for Parkinson’s disease dementia, and Rascovsky and Gorno-Tempini criteria for frontotemporal dementia variants [ 27 – 32 ]. In total, 27,500 patients from 46 outpatient clinics from all four regional health authorities in Norway have been registered in NorCog since 2014 [ 5 ]. In 2024, 43.4% were diagnosed with dementia, and 41.5% with MCI, while the rest had subjective cognitive impairment, no cognitive impairment or other specified diagnosis such as mood disorders [ 5 ]. Based on the 2024 numbers, we expect that approximately 85% of the NorCog patients from 2014–2024 will be eligible for inclusion. Selection of the study cohort is shown in Fig 1 . Download: PNG larger image TIFF original image Fig 1. Extraction of the study cohort from NorCog. https://doi.org/10.1371/journal.pone.0356275.g001 Extraction of variables from NorCog ( Table 1 ). Demographic, social and clinical variables potentially associated with PIMcog use will be extracted from NorCog and compared between PIMcog users and non-users of PIMcog. The selected demographic variables allow us to analyze differences related to local pharmacotherapeutic traditions and prescription patterns. The social variables are chosen due to possible differences in drug use related to age group, sex, living conditions, and the presence of family carers [ 37 ]. Download: PNG larger image TIFF original image Table 1. Selected variables extracted from NorCog. https://doi.org/10.1371/journal.pone.0356275.t001 Somatic illnesses and comorbidity burden have been shown to be associated with polypharmacy and the risk of inappropriate drug use [ 6 , 38 ]. Measure of somatic health and comorbidity will include recorded diagnoses and the Clinical Frailty Scale (CFS) score from NorCog [ 33 ]. In addition, the Charlson Comorbidity Index (CCI) will be derived from diagnoses registered in the NPR [ 39 ]. NPR is a national health registry that contains individual-level data for all patients who receive treatment, or are awaiting, the specialist health care services in Norway [ 40 ]. BPSD will be assessed using scores from the Neuropsychiatric Inventory Questionnaire (NPI-Q) and the Cornell Scale for Depression in Dementia (CSDD) [ 34 , 35 , 41 ]. Dementia etiology and severity will also be extracted from NorCog. Drug prescriptions extracted from the Norwegian Prescribed Drug Registry (NorPD). The NorPD consists of information about all prescription drugs dispensed from pharmacies to individuals but does not include medications dispensed in institutions. Therefore, only community-dwelling patients are included in this study. All information about drug use in the study cohort will be extracted from the NorPD, including date of dispensing, medicinal product name and formulation, complete Anatomical Therapeutic Chemical (ATC) code, and the quantity of dispensed medications. Drug prescriptions dispensed to the study participants from pharmacies during the twelve months preceding the diagnostic assessment will be extracted from the NorPD. The day of the diagnostic assessment conducted at the outpatient clinics is defined as the index date. Medications taken regularly are typically prescribed for three-month periods, thus we assume that capturing dispensed medications during the twelve months prior to the index date provides a valid estimate of drug exposure over time. The total number of drugs and the prevalence of polypharmacy will be calculated. Drugs that, according to the 2023 update of the Beers Criteria and STOPP criteria version 3 (STOPPv3), should be avoided in individuals with MCI and dementia will be defined as PIMcog. Accordingly, benzodiazepines (BZDs), benzodiazepine derivatives, benzodiazepine-related drugs, antipsychotics, and drugs with strong anticholinergic properties will be categorized as PIMcog. Antipsychotics listed as anticholinergic drugs in BeersCriteria will be classified as anticholinergics. The complete list of PIMcog has been developed through adaptation to the Norwegian drug market (Supplementary S1 Table ). Analysis plan Statistical power and sample size. This study is descriptive and aims to characterize PIMcog exposure over time; therefore, no statistical power calculations have been conducted. However, we have certain assumptions regarding sample size. In a previous study, we identified a prevalence of PIMcog use of 16% in a selected cohort of 397 patients with MCI and dementia attending Norwegian outpatient clinics from 2009 to 2016 [ 42 ]. That cohort contained a relatively high proportion of individuals with young-onset dementia and frontotemporal dementia and had a median age of 71 years. As the median age in the present study cohort is expected to be higher, and the proportion of individuals with frontotemporal dementia lower, we therefore expect the prevalence of PIMcog use to exceed 16% [ 37 ]. By including about 23,000 community-dwelling patients recorded in NorCog during 2014–2024, we estimate that approximately 20% (n = 4600) individuals will have been exposed to PIMcog during the year preceding the index date, enabling robust descriptive analyses of a broad group of PIMcog users. The prevalence of specific PIMcog classes and individual PIMcog agents is more difficult to anticipate. Based on previous studies, we expect prevalence rates of 5–10% for each PIMcog class, with z-hypnotics among the most frequently used PIMcog, with an expected prevalence of 20–25% [ 42 , 43 ]. Consequently, we anticipate sample sizes of at l
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