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Kidney disease and dementia are both common in older adults, posing a significant burden on individuals and society. Growing evidence suggests that there may be links between the kidney and the brain. However, few studies have explored how these two conditions are connected in the general population. Understanding this link could help improve care for people living with either or both conditions.
This observational project aims to explore the two-way relationship between kidney disease and dementia. The main questions the investigators want to answer are:
To answer these questions, the investigators will analyze data collected over a period of 12 years, including people diagnosed with dementia, kidney disease, or both, using several large Swedish and international health registries:
This study will apply both traditional and advanced epidemiological methods, including multivariable regression, survival analysis, mixed-effects models, and machine learning (ML) techniques to examine long-term trends and associations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Swedish Dementia Registry (SveDem) Cohort | SveDem was established in 2007 with the purpose of increasing the quality of dementia care in Sweden. SveDem aims to register all dementia patients in Sweden at the time of dementia diagnosis and includes annual follow-ups. The registry stores data on demographics, living conditions, cognitive evaluation by Mini-Mental State Examination (MMSE), type of dementia, community support and pharmacological management. |
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| The SCREAM project | SCREAM is a healthcare utilization cohort of all Stockholm residents that accessed SLL healthcare and had a measurement of serum creatinine in either in- or outpatient care. The database includes 2 million individuals (and >60 million laboratory tests). The kidney function and other laboratory tests are already collected. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kidney disease | Other | This is a registry-based observational study investigating the association between kidney disease and dementia-related outcomes. Kidney disease is not assigned or manipulated by the researchers but is classified as an exposure based on diagnostic codes (e.g., ICD codes), and related laboratory test recorded in health registers. |
| Measure | Description | Time Frame |
|---|---|---|
| Mini Mental Status Examination | The Mini-Mental State Examination (MMSE) is a standardized test used to screen for cognitive impairment and dementia. It assesses five domains of cognitive function including: orientation, registration, attention and calculation, recall, and language. The score range from 0 to 30. A score of 23 or lower is indicative of cognitive impairment. The MMSE takes only 5-10 minutes to test. MMSE is used at both baseline and follow-up visits. | MMSE will be assessed at baseline (dementia diagnosis) and at each follow-up visit every 12 months, up to 15 years or until death, whichever occurs first. Data will be reported at each time point and at study completion. |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause mortality | All-cause mortality will be defined as death from any cause, identified through linkage with the national death registry. Date of death will be recorded to calculate time-to-death from baseline. | Will be assessed continuously from baseline up to 15 years until the end of follow-up. |
| Incidence of advanced dementia |
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Inclusion Criteria:
Exclusion Criteria:
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This project uses the Swedish Dementia Registry (SveDem), merged with the Stockholm CREAtinine Measurements (SCREAM) project, to access healthcare data and obtain measurements of serum creatinine from both inpatient and outpatient care. It also uses the Swedish National Patient Registry (NPR) to include diagnoses made in specialist clinics and hospitals, the Prescribed Drug Registry (which includes all prescribed medications), and the Total Population Register and Causes of Death Registry (CDR) to obtain dates of death.
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| Name | Affiliation | Role |
|---|---|---|
| Hong Xu | Karolinska Institutet | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska Institutet | Stockholm | 171 77 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 7974647 | Background | Greenwald R. The handling of corneal donor tissue before penetrating keratoplasty. Todays OR Nurse. 1994 Sep-Oct;16(5):33-5. | |
| 28192452 | Background | Tsai HH, Yen RF, Lin CL, Kao CH. Increased risk of dementia in patients hospitalized with acute kidney injury: A nationwide population-based cohort study. PLoS One. 2017 Feb 13;12(2):e0171671. doi: 10.1371/journal.pone.0171671. eCollection 2017. |
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The data contains specific categories of personal data according to Article 9 of the General data protection regulation (GDPR) and KI is thus prohibited from sharing the data without an explicit consent from the registered or approval from the Swedish Ethical Review Authority (according to Section 3 and section 6 of the Ethical Review Act (2003:456)).
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Advanced dementia will be defined based on MMSE score ≤10. MMSE scores range from 0 to 30, with lower scores indicating worse cognitive function. MMSE score will be identified from clinical follow-up records. |
| Will be assessed annually from baseline (dementia) up to 15 years or until death, whichever occurs first. |
| 33741639 | Background | Xu H, Garcia-Ptacek S, Jonsson L, Wimo A, Nordstrom P, Eriksdotter M. Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality. Neurology. 2021 Apr 27;96(17):e2220-e2230. doi: 10.1212/WNL.0000000000011832. Epub 2021 Mar 19. |
| 15809354 | Background | Saeed RW, Varma S, Peng-Nemeroff T, Sherry B, Balakhaneh D, Huston J, Tracey KJ, Al-Abed Y, Metz CN. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med. 2005 Apr 4;201(7):1113-23. doi: 10.1084/jem.20040463. |
| 23727170 | Background | Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, Matsushita K, Wen CP. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013 Jul 27;382(9889):339-52. doi: 10.1016/S0140-6736(13)60595-4. Epub 2013 May 31. |
| 23727165 | Background | Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Kottgen A, Levey AS, Levin A. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet. 2013 Jul 13;382(9887):158-69. doi: 10.1016/S0140-6736(13)60439-0. Epub 2013 May 31. |
| 28960209 | Background | Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloid-beta metabolism beyond the brain. Nat Rev Neurol. 2017 Sep 29;13(10):612-623. doi: 10.1038/nrneurol.2017.111. |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D058186 | Acute Kidney Injury |
| D003704 | Dementia |
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
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