Clinical trial NCT05817188: Medication Repurposing to Stop Cognitive Decline in Dementia
Official title: Translational Identification of Medication Repurposing Candidates to Slow Cognitive Decline in Dementia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Dementia
Dementia Disorders
Keywords: medication
repurposing
cognitive decline
dementia
Mini-Mental State Examination
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: KTH Royal Institute of Technology
name: Region Stockholm
First posted: 2023-04-18
Enrollment: 100000
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study includes \>100,000 patients in SveDem and ca. 144,000 measures of Mini-mental State Examination (MMSE) including base registration and follow-ups. Our current merged dataset contains 80,004 individuals, but we periodically conduct new merges which will increase the sample size in the future: this may be necessary for rarer medications.

Brief summary: Dementia creates a great personal and societal burden and there are currently no treatments to stop memory loss. Many patients with dementia take medications to treat other conditions, e.g. high blood pressure and cholesterol. Some of these medications may have central effects on the pathophysiological processes leading to dementia.

Medication repurposing is a cost and time-effective way to discover new treatments. Swedish registers are a unique tool to detect medication candidates for repurposing. The Swedish Dementia Registry (SveDem) has \>100000 patients and ca. 144000 measures of cognition over time (measured with the Mini-Mental State Examination-MMSE), making it perfect to examine whether certain medications are associated with less cognitive decline in patients with dementia. Cholesterol and kidney function affect treatment and cognition and are available for 25000 patients. The investigators propose a study combining traditional cohort studies and newer artificial intelligence (machine learning) techniques to detect medications associated with slower cognitive decline in patients from SveDem. The investigators will test pre-specified hypotheses since the investigators suspect specific medications are better candidates to prevent cognitive decline, but the investigators will also let the machine learning algorithms explore the data to find associations that the investigators do not suspect in advance. Finally, the candidate medications will be tested in animal and cellular models to determine the mechanisms of their effects.


Eligibility criteria: Inclusion Criteria:

All patients with dementia registered in SveDem.

Exclusion Criteria:

Lack of Swedish personal identification number or coordination number.

Primary outcomes:
measure: Cognitive decline
timeFrame: Through study completion, at least 1 year
Secondary outcomes:
measure: Rate of nursing home placement
timeFrame: Through study completion, at least 1 year
measure: Mortality
timeFrame: Through study completion, at least 1 year
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet
Study officials:
affiliation: Karolinska Institutet
name: Sara Garcia-Ptacek, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Religa D, Fereshtehnejad SM, Cermakova P, Edlund AK, Garcia-Ptacek S, Granqvist N, Hallback A, Kawe K, Farahmand B, Kilander L, Mattsson UB, Nagga K, Nordstrom P, Wijk H, Wimo A, Winblad B, Eriksdotter M. SveDem, the Swedish Dementia Registry - a tool for improving the quality of diagnostics, treatment and care of dementia patients in clinical practice. PLoS One. 2015 Feb 19;10(2):e0116538. doi: 10.1371/journal.pone.0116538. eCollection 2015.
citation: Garcia-Ptacek S, Kareholt I, Farahmand B, Cuadrado ML, Religa D, Eriksdotter M. Body-mass index and mortality in incident dementia: a cohort study on 11,398 patients from SveDem, the Swedish Dementia Registry. J Am Med Dir Assoc. 2014 Jun;15(6):447.e1-7. doi: 10.1016/j.jamda.2014.03.001. Epub 2014 Apr 8.
citation: Roheger M, Zupanic E, Kareholt I, Religa D, Kalbe E, Eriksdotter M, Garcia-Ptacek S. Mortality and nursing home placement of dementia patients in rural and urban areas: a cohort study from the Swedish Dementia Registry. Scand J Caring Sci. 2018 Dec;32(4):1308-1313. doi: 10.1111/scs.12574. Epub 2018 Apr 14.
citation: Garcia-Ptacek S, Modeer IN, Kareholt I, Fereshtehnejad SM, Farahmand B, Religa D, Eriksdotter M. Differences in diagnostic process, treatment and social Support for Alzheimer's dementia between primary and specialist care: resultss from the Swedish Dementia Registry. Age Ageing. 2017 Mar 1;46(2):314-319. doi: 10.1093/ageing/afw189.
citation: Cermakova P, Nelson M, Secnik J, Garcia-Ptacek S, Johnell K, Fastbom J, Kilander L, Winblad B, Eriksdotter M, Religa D. Living Alone with Alzheimer's Disease: Data from SveDem, the Swedish Dementia Registry. J Alzheimers Dis. 2017;58(4):1265-1272. doi: 10.3233/JAD-170102.
citation: Garcia-Ptacek S, Kareholt I, Cermakova P, Rizzuto D, Religa D, Eriksdotter M. Causes of Death According to Death Certificates in Individuals with Dementia: A Cohort from the Swedish Dementia Registry. J Am Geriatr Soc. 2016 Nov;64(11):e137-e142. doi: 10.1111/jgs.14421. Epub 2016 Nov 1.
citation: Mo M, Abzhandadze T, Hoang MT, Sacuiu S, Jurado PG, Pereira JB, Naia L, Kele J, Maioli S, Xu H, Eriksdotter M, Garcia-Ptacek S. Antidepressant use and cognitive decline in patients with dementia: a national cohort study. BMC Med. 2025 Feb 25;23(1):82. doi: 10.1186/s12916-025-03851-3.
citation: Grau-Jurado P, Mostafaei S, Xu H, Mo M, Petek B, Kalar I, Naia L, Kele J, Maioli S, Pereira JB, Eriksdotter M, Chatterjee S, Garcia-Ptacek S. Medications and cognitive decline in Alzheimer's disease: Cohort cluster analysis of 15,428 patients. J Alzheimers Dis. 2025 Feb;103(3):931-940. doi: 10.1177/13872877241307870. Epub 2025 Jan 8.
citation: Petek B, Habel H, Xu H, Villa-Lopez M, Kalar I, Hoang MT, Maioli S, Pereira JB, Mostafaei S, Winblad B, Gregoric Kramberger M, Eriksdotter M, Garcia-Ptacek S. Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study. Alzheimers Res Ther. 2023 Dec 20;15(1):220. doi: 10.1186/s13195-023-01360-0.