Genetic risk factors for cerebral small vessel disease - Long term health follow up
University of Cambridge · Academic
In term In term in the September 2026 edition: the latest version runs to 31 October 2029.
- Reference
- DARS-NIC-606084-D1D6T
- Current version
- v2.5
- Term of current version
- 6 August 2026 to 31 October 2029
- Start date
- 10 May 2023
- Data controller
- Joint Data Controller
- Commercial purposes
- No
- Sublicensing
- No
- Files released to date
- 17
Data controllers
Why the data was released
Objective for processing
Cerebral small vessel disease (SVD) is a term that describes disease of the small brain blood vessels, which supply the deep parts of the brain. SVD is a serious health problem responsible for about a fifth of all strokes (lacunar stroke) worldwide and is the major cause of vascular cognitive impairment and dementia, and is also an important pathology into underlying intracerebral haemorrhage (bleeding into the brain tissue), which is the second most common cause of stroke and the most deadly.
Despite its importance, the cause of SVD is largely unknown, and this knowledge gap is a major factor behind the lack of specific therapies to delay SVD progression. Much less is understood about SVD than for other types of stroke.
One way to identify entirely novel mechanisms in diseases such as stroke, is genetics. The Genome-Wide Association Study (GWAS, a study design used to detect associations between genetic variants and common diseases in a population) approach has been successfully applied to many complex diseases over the last decade. However, GWAS to date in SVD has not been as successful as in other vascular diseases or in other types of stroke. This is surprising as epidemiological data from studies looking at the distribution (frequency) and determinants (causes and risk factors), suggests genetic risk factors are particularly important for the SVD stroke type. Previous family history of stroke is a risk factor for SVD, particularly in younger individuals. Twin and family studies suggest genetic factors account for 55-71% of total risk of leukoaraiosis (pathological appearance of the brain white matter), a component of the SVD phenotype (set of observable characteristics specific to SVD stroke). This discrepancy is likely due to a combination of relatively small sample size studies (<2000 cases) and issues related to phenotyping (characterisation) and heterogeneity of SVD. Heritability is a measure of how well differences in people’s genes account for differences in their traits. Previous genetic studies in stroke populations that applied a method that can estimate heritability from GWAS data, were not able to show any significant heritability for the SVD stroke subtype.
Recently, it has been shown that if you apply more accurate phenotyping (characterisation), using brain magnetic resonance imaging (MRI) to confirm cases, then the estimated heritability of SVD stroke is in the same range of diseases like Alzheimer's disease, schizophrenia, and multiple sclerosis, in which large-scale GWAS have been highly successful.
Using such an approach, the Cambridge stroke research group at University of Cambridge recently performed the first large scale GWAS in lacunar stroke which identified 12 genetic loci which are associated with an increase in SVD stroke risk.
(1). This samples from MRI-defined lacunar strokes and controls from several studies including DNA Lacunar 1 and 2 (UK studies managed by the Cambridge stroke research group), and studies from collaborators within the International Stroke Genetics Consortium (ISGC). This analysis showed the success of an approach with MRI based characterisation of SVD stroke cases.
The Cambridge Stroke Research group is continuing with this work in two ways funded by a British Heart Foundation programmed grant:
- Increasing the sample size of MRI confirmed lacunar stroke by continuing recruitment to DNA lacunar 2 to a sample size of 2000 (the DNA Lacunar 2 study has currently recruited about 1300 participants).
- Collection of long-term follow-up data on dementia to allow the identification of risk factors for developing dementia, and develop predictive scores.
A dreaded complication of SVD is dementia. Vascular dementia is the second most common form of dementia after Alzheimer's disease. It is caused when decreased blood flow damages brain tissue. SVD is the most common pathology underlying vascular dementia, and SVD changes act additively with other neurodegenerative pathology such as Alzheimer’s disease to increase the chance these pathologies result in clinical dementia. Therefore, SVD related cognitive decline is an enormous health burden. Despite its importance, not all patients with SVD develop dementia - in the St George's Cognition and Neuroimaging in Stroke (SCANS) Study, the Cambridge Stroke Research group demonstrated that 20% developed dementia over a 5-year follow-up (2).
To take the field forward the following two related questions need to be addressed:
• What are the biological factors that determine whether SVD results in dementia?
• How can doctors predict which patients with SVD will progress to dementia?
The Stroke Research group from University of Cambridge and other international research teams working on similar topics (using different datasets), have shown that disease severity on brain imaging, and particularly the degree of white matter tract damage, and therefore brain network disruption, is a factor in determining whether cognitive impairment occurs - but fails to account for all the variability.
The current hypothesis is that genomic and other data generated from Omics technologies (high-throughput biochemical assays that measure simultaneously many different molecules in a biological sample) will both provide additional insights into the biological factors resulting in dementia in SVD, and also improve clinical risk prediction.
The DNA Lacunar 2 study provides a unique opportunity to determine risk factors, both genetic and other, for dementia in a well-characterised group of MRI-confirmed SVD.
The Stroke Research group at the University of Cambridge is responsible for the management of the DNA Lacunar 2 study. Ethics approval was obtained in July 2016 and the first study participant was recruited in August 2016. Currently there are about 1,300 participants recruited from 44 actively recruiting hospitals in England and Wales, and a further number of participants (about 1,200) have been confirmed eligible after review of their MRI. The funding of the study from the British Heart Foundation has been extended until the end of 2026, which will allow recruitment to carry on until the end of 2025 with a target of 2,000 participants recruited. The total number of participants throughout may fluctuate as a result of cohort members passing away or withdrawing from the study.
In 2020, the ethics approval for the DNA Lacunar 2 study was amended to collect follow-up data including dementia incidence from the cohort of confirmed eligible study participants. This will allow the investigation of risk factors for vascular dementia and to examine the predictive value of clinical, MRI, and genomic markers in identifying those SVD cases who will convert to dementia.
Currently the DNA Lacunar 2 management team has been collecting this follow-up data by contacting participants and their GPs. The DNA Lacunar 2 management team would like to collect long-term follow-up via health records to increase the coverage. Initially the data collected from NHS England health records will be used in conjunction with the follow-up done directly with the participants and/or GPs, particularly in those cases where the DNA Lacunar 2 management team cannot easily contact the study participant. However if the NHS England approach is successful, this may mean the DNA Lacunar 2 management team can avoid individual study participant follow-up which will save considerable time and reduce burden on the study participant.
The main aim of this Agreement is to answer the following research question:
Can clinical, MRI and genetic determinants which predict future stroke, and dementia be identified in patients with SVD by following up the study participants every two years?
Data collected at trial entry includes: Demographics including contact details and GP information, risk factors, stroke presentation, blood test results, family history, medications and brief cognition assessments (such as the Brief Memory and Executive Test and the Geriatric Depression Scale). The Brief Memory and Executive Test is a short cognitive screen to detect the cognitive deficit seen in patients with vascular cognitive impairment due to SVD; and the Geriatric Depression Scale is a 30-item self-rated scale assessing depression in elderly individuals. Anonymized MRI data as well as a blood sample for the genetic analysis are also collected for each DNA Lacunar 2 study participant.
The DNA Lacunar 2 study is jointly sponsored by the University of Cambridge and University Cambridge Hospitals NHS Foundation Trust. The Chief Investigator (CI) of the study, has an Honorary Contract with University Cambridge Hospitals NHS Foundation Trust.
The University of Cambridge and University Cambridge Hospitals NHS Foundation Trust (CUH) are joint data controllers for the study as both organisations are responsible for decision-making regarding the collection and processing of data for this study. However, only the University of Cambridge will process the data of the study. All data obtained for the study will be stored by the University of Cambridge only and all data processing will only occur within the University of Cambridge network. University Cambridge Hospitals NHS Foundation Trust will not be processing the data.
The lawful basis for processing this data under GDPR is:
- Article 6(1)(e): processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller. The results of this study will provide information about potential risk factors for the diagnosis of dementia, recurrent strokes and occurrence of cardiovascular events in patients with small vessel disease. University of Cambridge is a public authority (university) carrying out a research project.
- Article 9(2)(j): processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The study is a scientific research project.
User involvement: The study team have discussed the design of the genetic studies with Patient and Public Involvement (PPI) groups previously at St George’s University Hospital in London. This led to the decision to treat all genetic results anonymously.
The DNA Lacunar 2 study relies on participant consent to satisfy the common law duty of confidentiality. Participants included patients with lacunar stroke with an anatomically corresponding lacunar infarct confirmed on MRI., where the stroke occurred within two years of recruitment and the MRI within one year of stroke. Patients are recruited from in and out patient stroke, neurology and medical services. In addition to prospective screening they can be recruited from retrospective review of patient records. Any patient who was unwilling or unable to consent was not approached.
DNA Lacunar 2 study participants have all signed a consent form giving permission for collection of information about their health status by consulting the records held by NHS England.
All study participants are more than 18 years old when they consented to the study. Further narrowing by age is not possible as the DNA Lacunar 2 study includes study participants of variable age with the youngest being in their 30s and the oldest in their 90s. Lacunar strokes occur more frequently in older individuals with the mean age for a lacunar stroke of 65 years old & Lacunar infarctions are not commonly seen in the paediatric population, therefore the focus for the study and the participants recruited is individuals over 18 years old. Participation to the study requires collection of medical history, family history, blood sample collection and cognitive assessment, therefore the study has recruited participants who are able to consent by themselves as it is more appropriate with the requirements of the study.
The DNA Lacunar 2 study currently has 44 recruiting sites across England however the study recently gained ethics approval for recruitment in Wales and collection of Welsh data from NHS England (July 2022). Therefore the number of recruitment sites will increase from 44 to 58 during the course of this Agreement. Study participants are located all over England and Wales and the search cannot be further limited geographically.
The DNA Lacunar 2 management team intend to collect long-term follow-up information every two years because deterioration in cognition leading to a diagnosis of dementia is a very gradual process and studies of similar populations have shown significant cognitive changes over this longer timescale.
The DNA Lacunar 2 management team are requesting record level data to link a single individual. There may be one or many records per individual. This is because the DNA Lacunar 2 management team needs to link long-term health data for each study participant to previous data collected such as MRI parameters and cognitive performance at trial entry.
The other alternatives to collect long-term health data are:
1) to contact directly each study participant, however this is intrusive for participants; it is limited because inevitably some participants will not be reachable and the data collected are not always reliable; it is also very time and resource consuming for the research team;
2) to contact GP but again this time consuming for GPs and the research team and will not solve the problem of study participant who have moved away since taking part of the study.
This data is required to identify DNA Lacunar 2 study participants who had an appointment at a hospital for a specific purpose (in relation to some cardiovascular event, in relation to a diagnosis of dementia or in relation to a consultation with a memory clinic). The list of participants to collect information on will be provided on a yearly basis following identifiers being provided to NHS England.
Participants are followed up every two years, so the list of participants provided will be updated by the DNA Lacunar 2 management team every year. Participants who have passed away will be removed from the list, whereas new participants due for follow-up will be added.
The data requested is limited to the cohort participants. the study team will use this data to identify four types of diagnosis/procedures:
- cardiovascular events such as: stroke, heart attack or Myocardial Infarction, angina
- cardiovascular procedures: Coronary artery bypass graft (CABG) or heart bypass; Coronary angioplasty
- dementia
- referral to memory clinic
The DNA Lacunar 2 study is funded by the British Heart Foundation via a 5-years program grant. The initial grant was awarded in May 2016 and has been renewed recently until 2026. The funder does not make any decisions regarding the data and does not have access to any of the data. The British Heart Foundation is not involved in or determining the method of the processing of NHS England data.
Linking data on recurrent stroke, frequency of cardiovascular events and procedures and future diagnosis of dementia obtained from Hospital Episode Statistics (HES Admitted Patient Care and Outpatient and Admitted Patient Care) and mortality data (Civil Registration - Deaths) to the DNA Lacunar 2 dataset (including genotyping data, MRI data, cardiovascular risk factor, behavioural risk factor, and family history data) will enable the study team to answer the previously mentioned study objectives.
Multiple data sources are requested to improve coverage/completeness of capturing diagnoses, as relying in a single dataset has been demonstrated to have significant limitations, especially in the context of cardiovascular disease and dementia.
Data requested:
- Access to HES Admitted Patient Care and HES Outpatient have been requested to derive study endpoints such as:
* stroke endpoints (date of event and the type of stroke)
* occurrence of future cardiovascular diseases (including admission to hospital for cardiovascular event [Angina, Myocardial Infarction, CABG, Coronary angioplasty]; date of event; primary diagnosis)
* occurrence of dementia diagnosis [including referral to memory clinic assessment; date of diagnosis; type of dementia].
- Hospital Episode Statistics (HES) data and Civil Registration - Deaths mortality data will be used to determine hospitalisations and deaths attributed to each outcome.
Processing activities
The data controllers (University of Cambridge and University Cambridge Hospitals NHS Foundation Trust ) aim to utilize the information routinely collected by NHS England for use as follow-up for those patients participating in the DNA Lacunar 2 observational study.
The University of Cambridge will submit a file containing the identifiers of the around 1,300 participants recruited to the DNA Lacunar 2 study using its secure electronic file transfer system. This will include:
• STUDY_ID
• NHS number
• Hospital number
• Name: surname and family name
• Date of Birth
• Sex
• Last known Postcode
This cohort will be submitted once a year and will be updated by the University of Cambridge's Stroke Research group. The DNA Lacunar 2 management team from the University of Cambridge collects long-term follow up data every two years post recruitment to the study. Participants known to have died will be removed from the cohort. Participants due for their 2 year follow-up will be added to the cohort sent to NHS England (based on their date of consent to the study). The selection of participants to add to the submitted cohort will be based on the participant last visit date.
The DNA Lacunar 2 study is an ongoing study and participants are continuously recruited. New recruits will be added based on their last visit date.
The University of Cambridge will not supply details of any participant who has withdrawn consent for access to their data. Data collected until the time of withdrawal will be kept. Once the participant has withdrawn consent for access to their data, no further data will be collected and the study participant will be removed from the cohort submitted to NHS England. Participants who have withdrawn from the study will be removed from the list submitted to NHS England.
The list of participants to follow up will be provided by the Stroke Research group from University of Cambridge to NHS England.
NHS England will track the clinical study patients in their cohort, providing an update of participant status including (alive/death and cause of death - Civil Registration - Deaths) and HES Admitted Patient Care (APC) and HES Outpatients dataset.
Record level data will be uploaded by NHS England to the Secure Electronic File Transfer service (SEFT) for download by the study team at the University of Cambridge.
NHS England will also return the Study ID to University of Cambridge with the data.
The data will be analysed to identify the following study endpoints such as:
* stroke endpoints (date of event and the type of stroke)
* occurrence of future cardiovascular diseases (including admission to hospital for cardiovascular event [Angina, Myocardial Infarction, CABG, Coronary angioplasty]; date of event; primary diagnosis)
* occurrence of dementia diagnosis [including referral to memory clinic assessment; date of diagnosis; type of dementia].
* deaths mortality data will be used to determine hospitalisations and deaths attributed to each outcome.
The data will be held within the Secure Research Computing Platform (SRCP), which is managed by the University Information Services (UIS) at the University of Cambridge and is run with the Information Governance Office on behalf of the Clinical School. The SRCP provides an ISO:27001 certified Safe Haven for members of the School to store sensitive data, including Personally Identifiable Data.
The SRCP provides a dedicated network, separated from the production network by a firewall, for storing sensitive personal data and hosting computers involved in its management and analysis. All equipment connected to the SRCP must be located in the UIS SRCP physically secure server rooms.
Research group applications to store Sensitive Personal Data must be made on a per study basis, whereupon the data flows will be checked to make sure they are appropriate. Once approved, data is migrated to the SRCP network and access is provided by a secure Virtual Desktop.
To access the SRCP users must:
- Have been approved in writing by the Study’s Data Manager
- Read the SRCP security policy
- Read and agree to the SRCP acceptable use policy
- Configured their account with a 15 character password
- Received their 2-factor authentication token
Only the DNA Lacunar 2 study team at University of Cambridge will have access to the identifiable data held on the secure server. All members of the DNA Lacunar 2 study team will have a contract of employment with the University of Cambridge. Data stored on this secure server will not be shared with anyone beyond the study team of the DNA Lacunar 2 study based in the University of Cambridge.
All data imported or exported to or from the SRCP is made via a secure transfer server. All transfers are audited.
The data obtained from NHS England will be used to collect dementia and stroke endpoints for longitudinal analysis of predictors of dementia in patients with SVD.
The data received from NHS England will not be used for any purpose other than to meet objectives as stated in this Data Sharing Agreement and will not be shared with any other third party or organisation. All personnel accessing the data have been appropriately trained in data protection and confidentiality.
Only the final result of the research will be shared with our collaborators in aggregated format with small numbers suppressed (e.g. number of stroke recurrences, number of dementia diagnosis within the cohort). Only anonymised data will be released to collaborating researchers. Collaborating researchers include research teams across the world, whom the DNA Lacunar 2 management team are working with on common projects. No personal data will be ever be released to collaborating researchers.
Expected output
University of Cambridge estimate the first analysis of predictors of dementia will be published from 2026.
University of Cambridge anticipate publishing the findings from these analyses in Open Access peer-reviewed journals as well as presenting them at academic conferences as the project progresses (i.e., no restrictions on the extent and/or timing of publication) from 2026.
It is hoped that research findings will be submitted to major and internationally leading conferences such the UK stroke forum, the European Stroke Organisation Conference, the Stroke meeting (International Conference on stroke, neurology and cerebrovascular diseases). These world-leading events on stroke and cardiovascular disease bring together clinicians, academic scientists, decision-makers, industrial partners and other disciplines sharing research findings and advances in medical care promoting the improvement of stroke and cardiovascular disease and care.
Furthermore, findings will be published in medical and scientific journals from 2026. Previous studies from the Cambridge Stroke Research group have been published in high impact outputs in the field of neurology - such as Stroke (https://www.ahajournals.org/journal/str), Neurology (https://n.neurology.org/), Brain (https://academic.oup.com/brain), Lancet Neurology (https://www.thelancet.com/journals/laneur/home) - genetics (Nature Genetics (https://www.nature.com/ng/) - and general medicine journal such as British medicine journal (https://www.bmj.com/research/research).
Following publication, the study findings will be disseminated via University of Cambridge newsletters, the stroke Research group social media accounts, and engagement with the study funders’ media offices to update patients and the public on its work
All findings will be presented in aggregated format with small numbers suppressed at medical or scientific conferences, and University meetings. Participant identifiable details will never be presented or published.
Expected measurable benefits
The results of the study have the potential to have a major impact on lacunar stroke management and cerebral small vessel disease in two broad ways:
- Firstly in better prediction of individuals who will progress to dementia.
- Secondly in better understanding of the processes causing the disease and allowing new therapeutic approaches to be identified.
Any benefit may have a major impact on health both in the UK and globally. Cerebral small vessel disease is a major health problem. It causes approximately a fifth of all strokes (meaning it causes about 25,000 strokes a year in the UK) and is the most common cause of vascular dementia. Furthermore, most cases of dementia in the elderly involve multiple pathologies including both neurodegenerative pathologies such as Alzheimer’s disease and vascular pathologies such as small vessel disease. It has been clearly shown that the presence of small vessel disease markedly increases the chance that someone with Alzheimer’s pathology will develop clinical dementia. For this reason, it is believed that small vessel disease contributes to at least 50% of clinical dementia cases in the UK i.e. 50% of the current number of cases 850,000.
Furthermore, lacunar stroke is not benign; 30% of patients are left dependent, and the limited long-term data available suggest that up to 25% of patients have a second stroke within 5 years.
The ways in which advances from this project could improve stroke and dementia care are covered in the two categories below.
1. Improved prediction of dementia:
Currently clinicians do not know which individuals with lacunar stroke will progress to dementia and better methods of prediction are required. Genetic risk scores offer the potential to improve prediction. The Cambridge Stroke Research Group will use the information derived from the DNA Lacunar 2 study to develop genetic risk scores. The genetic data will be combined with cardiovascular risk factor and demographic data as well as MRI data from the scans collected as part of DNA Lacunar 2 study to develop predictive models. The Cambridge Stroke Research group has already developed such models but the increased power provided by the DNA Lacunar 2 study will greatly improve the team ability to develop reliable predictions.
The availability of prediction models would enable the identification of a group of individuals who are at high risk of dementia for intensive risk factor modifications, or for novel therapies. Identifying a high risk group is particularly important because novel therapies may be associated with side effects and should be specifically given to individuals who are at high risk of developing the complications, in this case dementia. However, there are currently limited therapeutic interventions available to those identified as being at high risk of dementia; and that while the longer-term benefit may be to future patients, and the current benefit will predominantly be to researchers.
2. Improved understanding and developing novel therapeutic approaches:
Despite the enormous health and social importance of lacunar stroke and cerebral small vessel disease there are virtually no treatments which have been shown to delay disease progression and prevent dementia. Intensive antihypertensive therapy has been shown to have some benefit but clinicians are still unable to prevent most cases of recurrent stroke and particularly clinicians are unable to prevent individuals progressing to dementia. Round tables involving researchers, funders, and patients have identified that a major obstacle to developing new treatments is incomplete understanding about what actually causes lacunar stroke and small vessel disease.
Genetics offers one way in which completely novel information can be identified about pathways and new therapeutic targets can be identified. The Cambridge Stroke Research Group has already shown this is feasible in small vessel disease in a recent genome-wide association study (GWAS) of our previous DNA Lacunar study (1) in combination with datasets from around the world. In this work, researchers were able to identify 12 novel genes associated with small vessel disease and implicate novel processes in the disease such as disruption of the neurovascular unit and structures within the vessel wall of the small vessels.
The much greater power provided by the current study will increase the ability to identify further novel genes and pathways which will allow the identification of novel therapies to target disruption in these pathways. This approach has been successful in other diseases and indeed many drug companies are now using genetic approaches to identify therapies that may be potentially beneficial.
As well as identifying completely novel processes, the genetic data can be used to screen whether potential drugs may be beneficial in the disease. This is by using a technique called Mendelian randomisation. This is now widely used within drug discovery.
Therefore, the study has major potential to identify novel pathways, and also to examine whether potential therapies may be beneficial prior to investing large amounts of money in clinical trials.
Any potential treatment derived from the analysis of the DNA Lacunar 2 study data set may have major benefits in reducing the burden of this crippling disease for the patient, for the healthcare system, and for social services.
Benefits reported so far
No academic reports using the data have been published yet, and as such, no benefits have been yielded to date. The study is still recruiting, however, the plan is for recruitment to end in August 2026. Participants will still be followed-up for mortality, stroke recurrence, and diagnosis of dementia.
Datasets on the current version
Legal basis for provision: Health and Social Care Act 2012 – s261(2)(c)
| Dataset | Type of data | Sensitivity | Frequency | Confidential data |
|---|---|---|---|---|
| Civil Registrations of Death | Identifiable | Sensitive | One-Off | Consent (Reasonable Expectation) |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | Identifiable | Sensitive | Ongoing | Consent (Reasonable Expectation) |
| Hospital Episode Statistics Outpatients (HES OP) | Identifiable | Sensitive | Ongoing | Consent (Reasonable Expectation) |
Files released
Files released counts only files released externally by DARS. Access granted in NHS England's own systems, such as its Secure Data Environment, is not included.
Patient opt-outs were not applied to any of the 17 files released under this agreement, across every version. About opt-outs
Files released against version 2.5 of this agreement, summarised by dataset.
| Dataset | Files | First released | Last released | Opt-outs applied |
|---|---|---|---|---|
| Civil Registrations of Death | 1 | August 2026 | August 2026 | No |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | 1 | August 2026 | August 2026 | No |
| Hospital Episode Statistics Outpatients (HES OP) | 1 | August 2026 | August 2026 | No |
Version history
The register lists each renewal of this agreement as a separate row. This site has 3 versions.
DARS-NIC-606084-D1D6T-v2.5 6 August 2026 to 31 October 2029 Added this month
- Title
- Genetic risk factors for cerebral small vessel disease - Long term health follow up
- Commercial
- No
- Sublicensing
- No
- Datasets
- 3
- Files released
- 3
Datasets: Civil Registrations of Death; Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Outpatients (HES OP)
What changed from DARS-NIC-606084-D1D6T-v1.4
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2026-08-06 | |
| End date | 2029-10-31 |
Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits, Benefits reported.
DARS-NIC-606084-D1D6T-v1.4 3 April 2026 to 9 May 2029
- Title
- Genetic risk factors for cerebral small vessel disease - Long term health follow up
- Commercial
- No
- Sublicensing
- No
- Datasets
- 3
- Files released
- 0
Datasets: Civil Registrations of Death; Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Outpatients (HES OP)
What changed from DARS-NIC-606084-D1D6T-v0.24
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2026-04-03 | |
| End date | 2029-05-09 |
Objective for processing
[45 paragraphs unchanged]
Linking data on recurrent stroke, frequency of cardiovascular events and procedures and
[6 words unchanged]
Hospital Episode Statistics (HES Admitted Patient Care and Outpatient and Admitted Patient
Care),
Care)
and mortality data (Civil Registration - Deaths) to the DNA Lacunar 2
[16 words unchanged]
will enable the study team to answer the previously mentioned study objectives.
[7 paragraphs unchanged]
Processing activities
[21 paragraphs unchanged]
The data will be held within the Secure
Data Hosting Service (SDHS),
Research Computing Platform (SRCP),
which is managed by the
Clinical School Computing Service (CSCS)
University Information Services (UIS)
at the University of Cambridge and is run with the Information Governance Office on behalf of the Clinical School. The
SDHS
SRCP
provides an ISO:27001 certified Safe Haven for members of the School to store sensitive data, including Personally Identifiable Data.
The
SDHS
SRCP
provides a dedicated network, separated from the production network by a firewall,
[7 words unchanged]
computers involved in its management and analysis. All equipment connected to the
SDHS
SRCP
must be located in the
Clinical School Computing Service’s
UIS SRCP
physically secure server rooms.
Research group applications to store Sensitive Personal Data must be made on
[12 words unchanged]
make sure they are appropriate. Once approved, data is migrated to the
SDHS
SRCP
network and access is provided by a secure Virtual Desktop.
To access the
SDHS
SRCP
users must:
[1 paragraph unchanged]
- Read the
SDHS
SRCP
security policy
-
Signed
Read and agree to
the
SDHS
SRCP
acceptable use policy
[3 paragraphs unchanged]
All data imported or exported to or from the
SDHS
SRCP
is made via a secure transfer server. All transfers are audited.
[3 paragraphs unchanged]
Expected output
University of Cambridge estimate the first analysis of predictors of dementia will be published from
2024.
2026.
University of Cambridge anticipate publishing the findings from these analyses in Open
[14 words unchanged]
progresses (i.e., no restrictions on the extent and/or timing of publication) from
2024.
2026.
[1 paragraph unchanged]
Furthermore, findings will be published in medical and scientific journals from
2024.
2026.
Previous studies from the Cambridge Stroke Research group have been published in
[24 words unchanged]
(https://www.nature.com/ng/) - and general medicine journal such as British medicine journal (https://www.bmj.com/research/research).
[2 paragraphs unchanged]
Benefits reported
Yielded Benefits is not a requirement for new applications.
No academic reports using the data have been published yet, and as such, no benefits have been yielded to date. The study is still recruiting, however, the plan is for recruitment to end in August 2026. Participants will still be followed-up for mortality, stroke recurrence, and diagnosis of dementia.
Unchanged: Expected measurable benefits.
Objective for processing
Cerebral small vessel disease (SVD) is a term that describes disease of the small brain blood vessels, which supply the deep parts of the brain. SVD is a serious health problem responsible for about a fifth of all strokes (lacunar stroke) worldwide and is the major cause of vascular cognitive impairment and dementia, and is also an important pathology into underlying intracerebral haemorrhage (bleeding into the brain tissue), which is the second most common cause of stroke and the most deadly.
Despite its importance, the cause of SVD is largely unknown, and this knowledge gap is a major factor behind the lack of specific therapies to delay SVD progression. Much less is understood about SVD than for other types of stroke.
One way to identify entirely novel mechanisms in diseases such as stroke, is genetics. The Genome-Wide Association Study (GWAS, a study design used to detect associations between genetic variants and common diseases in a population) approach has been successfully applied to many complex diseases over the last decade. However, GWAS to date in SVD has not been as successful as in other vascular diseases or in other types of stroke. This is surprising as epidemiological data from studies looking at the distribution (frequency) and determinants (causes and risk factors), suggests genetic risk factors are particularly important for the SVD stroke type. Previous family history of stroke is a risk factor for SVD, particularly in younger individuals. Twin and family studies suggest genetic factors account for 55-71% of total risk of leukoaraiosis (pathological appearance of the brain white matter), a component of the SVD phenotype (set of observable characteristics specific to SVD stroke). This discrepancy is likely due to a combination of relatively small sample size studies (<2000 cases) and issues related to phenotyping (characterisation) and heterogeneity of SVD. Heritability is a measure of how well differences in people’s genes account for differences in their traits. Previous genetic studies in stroke populations that applied a method that can estimate heritability from GWAS data, were not able to show any significant heritability for the SVD stroke subtype.
Recently, it has been shown that if you apply more accurate phenotyping (characterisation), using brain magnetic resonance imaging (MRI) to confirm cases, then the estimated heritability of SVD stroke is in the same range of diseases like Alzheimer's disease, schizophrenia, and multiple sclerosis, in which large-scale GWAS have been highly successful.
Using such an approach, the Cambridge stroke research group at University of Cambridge recently performed the first large scale GWAS in lacunar stroke which identified 12 genetic loci which are associated with an increase in SVD stroke risk.
(1). This samples from MRI-defined lacunar strokes and controls from several studies including DNA Lacunar 1 and 2 (UK studies managed by the Cambridge stroke research group), and studies from collaborators within the International Stroke Genetics Consortium (ISGC). This analysis showed the success of an approach with MRI based characterisation of SVD stroke cases.
The Cambridge Stroke Research group is continuing with this work in two ways funded by a British Heart Foundation programmed grant:
- Increasing the sample size of MRI confirmed lacunar stroke by continuing recruitment to DNA lacunar 2 to a sample size of 2000 (the DNA Lacunar 2 study has currently recruited about 1300 participants).
- Collection of long-term follow-up data on dementia to allow the identification of risk factors for developing dementia, and develop predictive scores.
A dreaded complication of SVD is dementia. Vascular dementia is the second most common form of dementia after Alzheimer's disease. It is caused when decreased blood flow damages brain tissue. SVD is the most common pathology underlying vascular dementia, and SVD changes act additively with other neurodegenerative pathology such as Alzheimer’s disease to increase the chance these pathologies result in clinical dementia. Therefore, SVD related cognitive decline is an enormous health burden. Despite its importance, not all patients with SVD develop dementia - in the St George's Cognition and Neuroimaging in Stroke (SCANS) Study, the Cambridge Stroke Research group demonstrated that 20% developed dementia over a 5-year follow-up (2).
To take the field forward the following two related questions need to be addressed:
• What are the biological factors that determine whether SVD results in dementia?
• How can doctors predict which patients with SVD will progress to dementia?
The Stroke Research group from University of Cambridge and other international research teams working on similar topics (using different datasets), have shown that disease severity on brain imaging, and particularly the degree of white matter tract damage, and therefore brain network disruption, is a factor in determining whether cognitive impairment occurs - but fails to account for all the variability.
The current hypothesis is that genomic and other data generated from Omics technologies (high-throughput biochemical assays that measure simultaneously many different molecules in a biological sample) will both provide additional insights into the biological factors resulting in dementia in SVD, and also improve clinical risk prediction.
The DNA Lacunar 2 study provides a unique opportunity to determine risk factors, both genetic and other, for dementia in a well-characterised group of MRI-confirmed SVD.
The Stroke Research group at the University of Cambridge is responsible for the management of the DNA Lacunar 2 study. Ethics approval was obtained in July 2016 and the first study participant was recruited in August 2016. Currently there are about 1,300 participants recruited from 44 actively recruiting hospitals in England and Wales, and a further number of participants (about 1,200) have been confirmed eligible after review of their MRI. The funding of the study from the British Heart Foundation has been extended until the end of 2026, which will allow recruitment to carry on until the end of 2025 with a target of 2,000 participants recruited. The total number of participants throughout may fluctuate as a result of cohort members passing away or withdrawing from the study.
In 2020, the ethics approval for the DNA Lacunar 2 study was amended to collect follow-up data including dementia incidence from the cohort of confirmed eligible study participants. This will allow the investigation of risk factors for vascular dementia and to examine the predictive value of clinical, MRI, and genomic markers in identifying those SVD cases who will convert to dementia.
Currently the DNA Lacunar 2 management team has been collecting this follow-up data by contacting participants and their GPs. The DNA Lacunar 2 management team would like to collect long-term follow-up via health records to increase the coverage. Initially the data collected from NHS England health records will be used in conjunction with the follow-up done directly with the participants and/or GPs, particularly in those cases where the DNA Lacunar 2 management team cannot easily contact the study participant. However if the NHS England approach is successful, this may mean the DNA Lacunar 2 management team can avoid individual study participant follow-up which will save considerable time and reduce burden on the study participant.
The main aim of this Agreement is to answer the following research question:
Can clinical, MRI and genetic determinants which predict future stroke, and dementia be identified in patients with SVD by following up the study participants every two years?
Data collected at trial entry includes: Demographics including contact details and GP information, risk factors, stroke presentation, blood test results, family history, medications and brief cognition assessments (such as the Brief Memory and Executive Test and the Geriatric Depression Scale). The Brief Memory and Executive Test is a short cognitive screen to detect the cognitive deficit seen in patients with vascular cognitive impairment due to SVD; and the Geriatric Depression Scale is a 30-item self-rated scale assessing depression in elderly individuals. Anonymized MRI data as well as a blood sample for the genetic analysis are also collected for each DNA Lacunar 2 study participant.
The DNA Lacunar 2 study is jointly sponsored by the University of Cambridge and University Cambridge Hospitals NHS Foundation Trust. The Chief Investigator (CI) of the study, has an Honorary Contract with University Cambridge Hospitals NHS Foundation Trust.
The University of Cambridge and University Cambridge Hospitals NHS Foundation Trust (CUH) are joint data controllers for the study as both organisations are responsible for decision-making regarding the collection and processing of data for this study. However, only the University of Cambridge will process the data of the study. All data obtained for the study will be stored by the University of Cambridge only and all data processing will only occur within the University of Cambridge network. University Cambridge Hospitals NHS Foundation Trust will not be processing the data.
The lawful basis for processing this data under GDPR is:
- Article 6(1)(e): processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller. The results of this study will provide information about potential risk factors for the diagnosis of dementia, recurrent strokes and occurrence of cardiovascular events in patients with small vessel disease. University of Cambridge is a public authority (university) carrying out a research project.
- Article 9(2)(j): processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The study is a scientific research project.
User involvement: The study team have discussed the design of the genetic studies with Patient and Public Involvement (PPI) groups previously at St George’s University Hospital in London. This led to the decision to treat all genetic results anonymously.
The DNA Lacunar 2 study relies on participant consent to satisfy the common law duty of confidentiality. Participants included patients with lacunar stroke with an anatomically corresponding lacunar infarct confirmed on MRI., where the stroke occurred within two years of recruitment and the MRI within one year of stroke. Patients are recruited from in and out patient stroke, neurology and medical services. In addition to prospective screening they can be recruited from retrospective review of patient records. Any patient who was unwilling or unable to consent was not approached.
DNA Lacunar 2 study participants have all signed a consent form giving permission for collection of information about their health status by consulting the records held by NHS England.
All study participants are more than 18 years old when they consented to the study. Further narrowing by age is not possible as the DNA Lacunar 2 study includes study participants of variable age with the youngest being in their 30s and the oldest in their 90s. Lacunar strokes occur more frequently in older individuals with the mean age for a lacunar stroke of 65 years old & Lacunar infarctions are not commonly seen in the paediatric population, therefore the focus for the study and the participants recruited is individuals over 18 years old. Participation to the study requires collection of medical history, family history, blood sample collection and cognitive assessment, therefore the study has recruited participants who are able to consent by themselves as it is more appropriate with the requirements of the study.
The DNA Lacunar 2 study currently has 44 recruiting sites across England however the study recently gained ethics approval for recruitment in Wales and collection of Welsh data from NHS England (July 2022). Therefore the number of recruitment sites will increase from 44 to 58 during the course of this Agreement. Study participants are located all over England and Wales and the search cannot be further limited geographically.
The DNA Lacunar 2 management team intend to collect long-term follow-up information every two years because deterioration in cognition leading to a diagnosis of dementia is a very gradual process and studies of similar populations have shown significant cognitive changes over this longer timescale.
The DNA Lacunar 2 management team are requesting record level data to link a single individual. There may be one or many records per individual. This is because the DNA Lacunar 2 management team needs to link long-term health data for each study participant to previous data collected such as MRI parameters and cognitive performance at trial entry.
The other alternatives to collect long-term health data are:
1) to contact directly each study participant, however this is intrusive for participants; it is limited because inevitably some participants will not be reachable and the data collected are not always reliable; it is also very time and resource consuming for the research team;
2) to contact GP but again this time consuming for GPs and the research team and will not solve the problem of study participant who have moved away since taking part of the study.
This data is required to identify DNA Lacunar 2 study participants who had an appointment at a hospital for a specific purpose (in relation to some cardiovascular event, in relation to a diagnosis of dementia or in relation to a consultation with a memory clinic). The list of participants to collect information on will be provided on a yearly basis following identifiers being provided to NHS England.
Participants are followed up every two years, so the list of participants provided will be updated by the DNA Lacunar 2 management team every year. Participants who have passed away will be removed from the list, whereas new participants due for follow-up will be added.
The data requested is limited to the cohort participants. the study team will use this data to identify four types of diagnosis/procedures:
- cardiovascular events such as: stroke, heart attack or Myocardial Infarction, angina
- cardiovascular procedures: Coronary artery bypass graft (CABG) or heart bypass; Coronary angioplasty
- dementia
- referral to memory clinic
The DNA Lacunar 2 study is funded by the British Heart Foundation via a 5-years program grant. The initial grant was awarded in May 2016 and has been renewed recently until 2026. The funder does not make any decisions regarding the data and does not have access to any of the data. The British Heart Foundation is not involved in or determining the method of the processing of NHS England data.
Linking data on recurrent stroke, frequency of cardiovascular events and procedures and future diagnosis of dementia obtained from Hospital Episode Statistics (HES Admitted Patient Care and Outpatient and Admitted Patient Care) and mortality data (Civil Registration - Deaths) to the DNA Lacunar 2 dataset (including genotyping data, MRI data, cardiovascular risk factor, behavioural risk factor, and family history data) will enable the study team to answer the previously mentioned study objectives.
Multiple data sources are requested to improve coverage/completeness of capturing diagnoses, as relying in a single dataset has been demonstrated to have significant limitations, especially in the context of cardiovascular disease and dementia.
Data requested:
- Access to HES Admitted Patient Care and HES Outpatient have been requested to derive study endpoints such as:
* stroke endpoints (date of event and the type of stroke)
* occurrence of future cardiovascular diseases (including admission to hospital for cardiovascular event [Angina, Myocardial Infarction, CABG, Coronary angioplasty]; date of event; primary diagnosis)
* occurrence of dementia diagnosis [including referral to memory clinic assessment; date of diagnosis; type of dementia].
- Hospital Episode Statistics (HES) data and Civil Registration - Deaths mortality data will be used to determine hospitalisations and deaths attributed to each outcome.
Expected output
University of Cambridge estimate the first analysis of predictors of dementia will be published from 2026.
University of Cambridge anticipate publishing the findings from these analyses in Open Access peer-reviewed journals as well as presenting them at academic conferences as the project progresses (i.e., no restrictions on the extent and/or timing of publication) from 2026.
It is hoped that research findings will be submitted to major and internationally leading conferences such the UK stroke forum, the European Stroke Organisation Conference, the Stroke meeting (International Conference on stroke, neurology and cerebrovascular diseases). These world-leading events on stroke and cardiovascular disease bring together clinicians, academic scientists, decision-makers, industrial partners and other disciplines sharing research findings and advances in medical care promoting the improvement of stroke and cardiovascular disease and care.
Furthermore, findings will be published in medical and scientific journals from 2026. Previous studies from the Cambridge Stroke Research group have been published in high impact outputs in the field of neurology - such as Stroke (https://www.ahajournals.org/journal/str), Neurology (https://n.neurology.org/), Brain (https://academic.oup.com/brain), Lancet Neurology (https://www.thelancet.com/journals/laneur/home) - genetics (Nature Genetics (https://www.nature.com/ng/) - and general medicine journal such as British medicine journal (https://www.bmj.com/research/research).
Following publication, the study findings will be disseminated via University of Cambridge newsletters, the stroke Research group social media accounts, and engagement with the study funders’ media offices to update patients and the public on its work
All findings will be presented in aggregated format with small numbers suppressed at medical or scientific conferences, and University meetings. Participant identifiable details will never be presented or published.
Benefits reported
No academic reports using the data have been published yet, and as such, no benefits have been yielded to date. The study is still recruiting, however, the plan is for recruitment to end in August 2026. Participants will still be followed-up for mortality, stroke recurrence, and diagnosis of dementia.
DARS-NIC-606084-D1D6T-v0.24 10 May 2023 to 9 May 2026
- Title
- Genetic risk factors for cerebral small vessel disease - Long term health follow up
- Commercial
- No
- Sublicensing
- No
- Datasets
- 3
- Files released
- 14
Datasets: Civil Registrations of Death; Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Outpatients (HES OP)
Objective for processing
Cerebral small vessel disease (SVD) is a term that describes disease of the small brain blood vessels, which supply the deep parts of the brain. SVD is a serious health problem responsible for about a fifth of all strokes (lacunar stroke) worldwide and is the major cause of vascular cognitive impairment and dementia, and is also an important pathology into underlying intracerebral haemorrhage (bleeding into the brain tissue), which is the second most common cause of stroke and the most deadly.
Despite its importance, the cause of SVD is largely unknown, and this knowledge gap is a major factor behind the lack of specific therapies to delay SVD progression. Much less is understood about SVD than for other types of stroke.
One way to identify entirely novel mechanisms in diseases such as stroke, is genetics. The Genome-Wide Association Study (GWAS, a study design used to detect associations between genetic variants and common diseases in a population) approach has been successfully applied to many complex diseases over the last decade. However, GWAS to date in SVD has not been as successful as in other vascular diseases or in other types of stroke. This is surprising as epidemiological data from studies looking at the distribution (frequency) and determinants (causes and risk factors), suggests genetic risk factors are particularly important for the SVD stroke type. Previous family history of stroke is a risk factor for SVD, particularly in younger individuals. Twin and family studies suggest genetic factors account for 55-71% of total risk of leukoaraiosis (pathological appearance of the brain white matter), a component of the SVD phenotype (set of observable characteristics specific to SVD stroke). This discrepancy is likely due to a combination of relatively small sample size studies (<2000 cases) and issues related to phenotyping (characterisation) and heterogeneity of SVD. Heritability is a measure of how well differences in people’s genes account for differences in their traits. Previous genetic studies in stroke populations that applied a method that can estimate heritability from GWAS data, were not able to show any significant heritability for the SVD stroke subtype.
Recently, it has been shown that if you apply more accurate phenotyping (characterisation), using brain magnetic resonance imaging (MRI) to confirm cases, then the estimated heritability of SVD stroke is in the same range of diseases like Alzheimer's disease, schizophrenia, and multiple sclerosis, in which large-scale GWAS have been highly successful.
Using such an approach, the Cambridge stroke research group at University of Cambridge recently performed the first large scale GWAS in lacunar stroke which identified 12 genetic loci which are associated with an increase in SVD stroke risk.
(1). This samples from MRI-defined lacunar strokes and controls from several studies including DNA Lacunar 1 and 2 (UK studies managed by the Cambridge stroke research group), and studies from collaborators within the International Stroke Genetics Consortium (ISGC). This analysis showed the success of an approach with MRI based characterisation of SVD stroke cases.
The Cambridge Stroke Research group is continuing with this work in two ways funded by a British Heart Foundation programmed grant:
- Increasing the sample size of MRI confirmed lacunar stroke by continuing recruitment to DNA lacunar 2 to a sample size of 2000 (the DNA Lacunar 2 study has currently recruited about 1300 participants).
- Collection of long-term follow-up data on dementia to allow the identification of risk factors for developing dementia, and develop predictive scores.
A dreaded complication of SVD is dementia. Vascular dementia is the second most common form of dementia after Alzheimer's disease. It is caused when decreased blood flow damages brain tissue. SVD is the most common pathology underlying vascular dementia, and SVD changes act additively with other neurodegenerative pathology such as Alzheimer’s disease to increase the chance these pathologies result in clinical dementia. Therefore, SVD related cognitive decline is an enormous health burden. Despite its importance, not all patients with SVD develop dementia - in the St George's Cognition and Neuroimaging in Stroke (SCANS) Study, the Cambridge Stroke Research group demonstrated that 20% developed dementia over a 5-year follow-up (2).
To take the field forward the following two related questions need to be addressed:
• What are the biological factors that determine whether SVD results in dementia?
• How can doctors predict which patients with SVD will progress to dementia?
The Stroke Research group from University of Cambridge and other international research teams working on similar topics (using different datasets), have shown that disease severity on brain imaging, and particularly the degree of white matter tract damage, and therefore brain network disruption, is a factor in determining whether cognitive impairment occurs - but fails to account for all the variability.
The current hypothesis is that genomic and other data generated from Omics technologies (high-throughput biochemical assays that measure simultaneously many different molecules in a biological sample) will both provide additional insights into the biological factors resulting in dementia in SVD, and also improve clinical risk prediction.
The DNA Lacunar 2 study provides a unique opportunity to determine risk factors, both genetic and other, for dementia in a well-characterised group of MRI-confirmed SVD.
The Stroke Research group at the University of Cambridge is responsible for the management of the DNA Lacunar 2 study. Ethics approval was obtained in July 2016 and the first study participant was recruited in August 2016. Currently there are about 1,300 participants recruited from 44 actively recruiting hospitals in England and Wales, and a further number of participants (about 1,200) have been confirmed eligible after review of their MRI. The funding of the study from the British Heart Foundation has been extended until the end of 2026, which will allow recruitment to carry on until the end of 2025 with a target of 2,000 participants recruited. The total number of participants throughout may fluctuate as a result of cohort members passing away or withdrawing from the study.
In 2020, the ethics approval for the DNA Lacunar 2 study was amended to collect follow-up data including dementia incidence from the cohort of confirmed eligible study participants. This will allow the investigation of risk factors for vascular dementia and to examine the predictive value of clinical, MRI, and genomic markers in identifying those SVD cases who will convert to dementia.
Currently the DNA Lacunar 2 management team has been collecting this follow-up data by contacting participants and their GPs. The DNA Lacunar 2 management team would like to collect long-term follow-up via health records to increase the coverage. Initially the data collected from NHS England health records will be used in conjunction with the follow-up done directly with the participants and/or GPs, particularly in those cases where the DNA Lacunar 2 management team cannot easily contact the study participant. However if the NHS England approach is successful, this may mean the DNA Lacunar 2 management team can avoid individual study participant follow-up which will save considerable time and reduce burden on the study participant.
The main aim of this Agreement is to answer the following research question:
Can clinical, MRI and genetic determinants which predict future stroke, and dementia be identified in patients with SVD by following up the study participants every two years?
Data collected at trial entry includes: Demographics including contact details and GP information, risk factors, stroke presentation, blood test results, family history, medications and brief cognition assessments (such as the Brief Memory and Executive Test and the Geriatric Depression Scale). The Brief Memory and Executive Test is a short cognitive screen to detect the cognitive deficit seen in patients with vascular cognitive impairment due to SVD; and the Geriatric Depression Scale is a 30-item self-rated scale assessing depression in elderly individuals. Anonymized MRI data as well as a blood sample for the genetic analysis are also collected for each DNA Lacunar 2 study participant.
The DNA Lacunar 2 study is jointly sponsored by the University of Cambridge and University Cambridge Hospitals NHS Foundation Trust. The Chief Investigator (CI) of the study, has an Honorary Contract with University Cambridge Hospitals NHS Foundation Trust.
The University of Cambridge and University Cambridge Hospitals NHS Foundation Trust (CUH) are joint data controllers for the study as both organisations are responsible for decision-making regarding the collection and processing of data for this study. However, only the University of Cambridge will process the data of the study. All data obtained for the study will be stored by the University of Cambridge only and all data processing will only occur within the University of Cambridge network. University Cambridge Hospitals NHS Foundation Trust will not be processing the data.
The lawful basis for processing this data under GDPR is:
- Article 6(1)(e): processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller. The results of this study will provide information about potential risk factors for the diagnosis of dementia, recurrent strokes and occurrence of cardiovascular events in patients with small vessel disease. University of Cambridge is a public authority (university) carrying out a research project.
- Article 9(2)(j): processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The study is a scientific research project.
User involvement: The study team have discussed the design of the genetic studies with Patient and Public Involvement (PPI) groups previously at St George’s University Hospital in London. This led to the decision to treat all genetic results anonymously.
The DNA Lacunar 2 study relies on participant consent to satisfy the common law duty of confidentiality. Participants included patients with lacunar stroke with an anatomically corresponding lacunar infarct confirmed on MRI., where the stroke occurred within two years of recruitment and the MRI within one year of stroke. Patients are recruited from in and out patient stroke, neurology and medical services. In addition to prospective screening they can be recruited from retrospective review of patient records. Any patient who was unwilling or unable to consent was not approached.
DNA Lacunar 2 study participants have all signed a consent form giving permission for collection of information about their health status by consulting the records held by NHS England.
All study participants are more than 18 years old when they consented to the study. Further narrowing by age is not possible as the DNA Lacunar 2 study includes study participants of variable age with the youngest being in their 30s and the oldest in their 90s. Lacunar strokes occur more frequently in older individuals with the mean age for a lacunar stroke of 65 years old & Lacunar infarctions are not commonly seen in the paediatric population, therefore the focus for the study and the participants recruited is individuals over 18 years old. Participation to the study requires collection of medical history, family history, blood sample collection and cognitive assessment, therefore the study has recruited participants who are able to consent by themselves as it is more appropriate with the requirements of the study.
The DNA Lacunar 2 study currently has 44 recruiting sites across England however the study recently gained ethics approval for recruitment in Wales and collection of Welsh data from NHS England (July 2022). Therefore the number of recruitment sites will increase from 44 to 58 during the course of this Agreement. Study participants are located all over England and Wales and the search cannot be further limited geographically.
The DNA Lacunar 2 management team intend to collect long-term follow-up information every two years because deterioration in cognition leading to a diagnosis of dementia is a very gradual process and studies of similar populations have shown significant cognitive changes over this longer timescale.
The DNA Lacunar 2 management team are requesting record level data to link a single individual. There may be one or many records per individual. This is because the DNA Lacunar 2 management team needs to link long-term health data for each study participant to previous data collected such as MRI parameters and cognitive performance at trial entry.
The other alternatives to collect long-term health data are:
1) to contact directly each study participant, however this is intrusive for participants; it is limited because inevitably some participants will not be reachable and the data collected are not always reliable; it is also very time and resource consuming for the research team;
2) to contact GP but again this time consuming for GPs and the research team and will not solve the problem of study participant who have moved away since taking part of the study.
This data is required to identify DNA Lacunar 2 study participants who had an appointment at a hospital for a specific purpose (in relation to some cardiovascular event, in relation to a diagnosis of dementia or in relation to a consultation with a memory clinic). The list of participants to collect information on will be provided on a yearly basis following identifiers being provided to NHS England.
Participants are followed up every two years, so the list of participants provided will be updated by the DNA Lacunar 2 management team every year. Participants who have passed away will be removed from the list, whereas new participants due for follow-up will be added.
The data requested is limited to the cohort participants. the study team will use this data to identify four types of diagnosis/procedures:
- cardiovascular events such as: stroke, heart attack or Myocardial Infarction, angina
- cardiovascular procedures: Coronary artery bypass graft (CABG) or heart bypass; Coronary angioplasty
- dementia
- referral to memory clinic
The DNA Lacunar 2 study is funded by the British Heart Foundation via a 5-years program grant. The initial grant was awarded in May 2016 and has been renewed recently until 2026. The funder does not make any decisions regarding the data and does not have access to any of the data. The British Heart Foundation is not involved in or determining the method of the processing of NHS England data.
Linking data on recurrent stroke, frequency of cardiovascular events and procedures and future diagnosis of dementia obtained from Hospital Episode Statistics (HES Admitted Patient Care and Outpatient and Admitted Patient Care), and mortality data (Civil Registration - Deaths) to the DNA Lacunar 2 dataset (including genotyping data, MRI data, cardiovascular risk factor, behavioural risk factor, and family history data) will enable the study team to answer the previously mentioned study objectives.
Multiple data sources are requested to improve coverage/completeness of capturing diagnoses, as relying in a single dataset has been demonstrated to have significant limitations, especially in the context of cardiovascular disease and dementia.
Data requested:
- Access to HES Admitted Patient Care and HES Outpatient have been requested to derive study endpoints such as:
* stroke endpoints (date of event and the type of stroke)
* occurrence of future cardiovascular diseases (including admission to hospital for cardiovascular event [Angina, Myocardial Infarction, CABG, Coronary angioplasty]; date of event; primary diagnosis)
* occurrence of dementia diagnosis [including referral to memory clinic assessment; date of diagnosis; type of dementia].
- Hospital Episode Statistics (HES) data and Civil Registration - Deaths mortality data will be used to determine hospitalisations and deaths attributed to each outcome.
Expected output
University of Cambridge estimate the first analysis of predictors of dementia will be published from 2024.
University of Cambridge anticipate publishing the findings from these analyses in Open Access peer-reviewed journals as well as presenting them at academic conferences as the project progresses (i.e., no restrictions on the extent and/or timing of publication) from 2024.
It is hoped that research findings will be submitted to major and internationally leading conferences such the UK stroke forum, the European Stroke Organisation Conference, the Stroke meeting (International Conference on stroke, neurology and cerebrovascular diseases). These world-leading events on stroke and cardiovascular disease bring together clinicians, academic scientists, decision-makers, industrial partners and other disciplines sharing research findings and advances in medical care promoting the improvement of stroke and cardiovascular disease and care.
Furthermore, findings will be published in medical and scientific journals from 2024. Previous studies from the Cambridge Stroke Research group have been published in high impact outputs in the field of neurology - such as Stroke (https://www.ahajournals.org/journal/str), Neurology (https://n.neurology.org/), Brain (https://academic.oup.com/brain), Lancet Neurology (https://www.thelancet.com/journals/laneur/home) - genetics (Nature Genetics (https://www.nature.com/ng/) - and general medicine journal such as British medicine journal (https://www.bmj.com/research/research).
Following publication, the study findings will be disseminated via University of Cambridge newsletters, the stroke Research group social media accounts, and engagement with the study funders’ media offices to update patients and the public on its work
All findings will be presented in aggregated format with small numbers suppressed at medical or scientific conferences, and University meetings. Participant identifiable details will never be presented or published.
Benefits reported
Yielded Benefits is not a requirement for new applications.
Register history
When this agreement appeared in, or was edited in, each monthly edition of the register. Built by comparing every edition this site holds.
-
September 2023 —
first listed. 1 version: DARS-NIC-606084-D1D6T-v0.24
-
May 2026
1 version added: DARS-NIC-606084-D1D6T-v1.4
-
September 2026
1 version added: DARS-NIC-606084-D1D6T-v2.5
Cite this page
NHS England (2026) Data Uses Register, September 2026 edition, agreement DARS-NIC-606084-D1D6T, “Genetic risk factors for cerebral small vessel disease - Long term health follow up”. Read via NHS Data Access Explorer (unofficial), https://healthdatauses.uk/agreements/dars-nic-606084-d1d6t/ (accessed [date]).
This address stays the same, but the page is rebuilt with each monthly edition, so the citation names the edition it shows. Every edition's data is kept in the facts store.
Source: datausesregister_september2026.xlsx, September 2026 edition of the NHS England Data Uses Register. Search that workbook for DARS-NIC-606084-D1D6T to see the original rows.