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Projects and Databases

EACare: Embodied Agent to support elderly mental wellbeing

Principal Investigator: Professor Hedvig Kjellström, KTH

A collaboration between Karolinska Institutet and KTH.
The main goal of the proposed multidisciplinary research is to develop an embodied agent – a robot head with communicative skills capable of interacting with elderly people at their convenience. analyzing their mental and psychological status via powerful audiovisual sensing and assessing their mental abilities to identify subjects in high risk or possibly at the first stages of depressive or dementing disorders, who would benefit from proper medical consultation. The framework will also provide tools for dementia preventive training.

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CIMED: Center for Innovative Medicine

Center for Innovative Medicine (CIMED) is a joint research effort initiated by Stockholm County Council, Karolinska Institutet and industry partners that aims at stimulating a research environment for cutting edge medical research and drug development. Research groups in a variety of fields such as cancer, immune disorders, obesity and metabolism, dementia and aging are financed through the center. Nordic Brain Network is one of the proud financed partners (2015-2020) since Miia Kivipelto received the junior research grant. The NBN CIMED project aims at developing clinically feasible multimodal intervention studies in early Alzheimer disease and to gain a better understanding on which are the underlying molecular mechanisms that are affected from multimodal interventions.

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EiT Health: Multimodal strategies to promote a healthy brain in aging: Innovative evidence-based tools (MULTI-MODE)

Principal Investigator: Professor Miia Kivipelto
Coordinator: Shireen Sindi

MULTI-MODE is funded by the European Institute of Technology (EIT-Health), and consists of partners from the following leading institutes across Europe: (Research Institutes of Sweden, Imperial College, Rotterdam University, Parc Sanitari Sant Joan de Déu). The goal is to develop and commercialize innovative evidence-based eHealth tools for:

(A) Dementia risk prediction in various at-risk populations (e.g. middle-aged and older adults with various risk profiles, memory clinic patients). This work will build on the original CAIDE Dementia Risk Score (developed by Prof. Kivipelto and colleagues).

(B) Multidomain lifestyle intervention targeting modifiable risk factors (vascular, metabolic, and psychological) to prevent cognitive decline and postpone dementia onset (based on the FINGER trial)

These products will be promoted and implemented in diverse settings, for usage by citizens and health professionals. The subsequent MUTLI-MODE dissemination and educational initiatives aim to empower citizens and their families, reduce health costs and societal burden. Considering the partners’ expertise and previously initiated programs, the current academic-industrial partnership will develop state-of-the art eHealth tools and guarantee rapid time-to-market.

http://ki.se/en/nvs/eit-health-project-aims-to-prevent-dementia-by-developing-new-innovations

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CAIDE: The Cardiovascular Risk Factors, Aging, and Dementia Study: a population-based, observational, prospective long-term study in Finland.

Principal investigator: Professor Miia Kivipelto
Coordinator: Alina Solomon

The CAIDE study investigates the lifestyle and cardiovascular risk factors for dementia, Alzheimer’s disease (AD) and structural brain changes using the follow-up period extending up to almost thirty years. The main aim of the study is to explore the modifiable risk and protective factors for dementia and AD, and also gene-environmental interactions, with special focus on the effects and putative interactions between the apoE epsilon4 allele and lifestyle risk factors.

The study includes a total of 1511 Finnish participants who were randomly selected from four separate, previous population-based samples originally studied at an average age of 50 years. The CAIDE re-examinations were carried out in 1998 and 2005-2008 when the participants were an average of 71 years old at the first, and 79 years old at the second re-examination. CAIDE examinations included detailed neurological, cardiovascular and neuropsychological examination and extensive self-reported questionnaires. In addition a subpopulation was scanned using the magnetic resonance imaging.

During the recent years this multidisciplinary study has provided sufficient evidence that vascular risk factors significantly contribute to the expression and progression of cognitive decline (including dementia and AD) but that active engagement in social, physical, and mentally stimulating activities may delay the onset of the disease.
Professor Miia Kivipelto leads the CAIDE project. The study is a joint collaboration between National Institute for Health and Welfare (THL), Finland, University of Eastern Finland and Aging Research Center, Karolinska Institutet, Stockholm, Sweden. Until now, the CAIDE data have resulted in nine dissertations, and over thirty original scientific articles published in high impact esteemed journals.

To learn more visit http://www.uef.fi/en/web/caide/


FINRISK: National extensive population study on the risk factors for chronic, non-communicable diseases in Finland. The survey is carried out every five years.


FINGER: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (NCT01041989, Clinicaltrials )

Principal investigator: Professor Miia Kivipelto
Coordinator: Tiia Ngandu

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (NCT01041989, Clinicaltrials): a multi-center randomized controlled trial (intervention study) carried out in Finland, in collaboration with Karolinska Institutet (Sweden), testing the effect of a multi-domain intervention in delaying cognitive impairment and disability in elderly at risk.

FINGER is a 2-year multi-center randomized controlled trial with 1260 participants aged 60-77 years recruited from previous population-based survey cohorts. Inclusion criteria were: CAIDE Dementia Risk Score >6 points, indicating the presence of modifiable risk factors; and cognitive performance at the mean level or slightly lower than expected for age. Participants were randomized (1:1) into either the multidomain intervention group or the control group. The intervention included nutritional guidance, physical exercise, cognitive training and social activities, and management of vascular risk factors. The control group received regular health advice.

Primary outcome after 2 years is cognitive performance measured by a comprehensive neuropsychological test battery (NTB) composite Z score. An extended follow-up (7 years) with a sustenance intervention is planned to evaluate longer-term effects on dementia/AD incidence, and secondary and exploratory outcomes including biomarkers and neuroimaging with MRI and PET. The 2-year intervention was finalized in February 2014. Here we report the main intention-to-treat (ITT) results on cognition after 2 years of intervention. Linear mixed-model statistical analyses were used. After 2 years, the NTB scores in the intervention group were 25% higher than in the control group. For some cognitive domains, the impact of the intervention was even more robust. This is the first large RCT showing that it is possible to prevent cognitive decline using a multidomain intervention among older at-risk individuals. These results highlight the value of the feasible and novel multidomain approach that is effective for several cognitive domains. Open PDF.


GEDOC: Database and biobank for clinical dementia research

Coordinator: Professor Miia Kivipelto

Clinical-based database including patients at the Memory Clinict, Karolinska University Hospital, Huddinge. GEDOC is used for clinical-based studies aiming to identify biomarkers for early diagnosis of AD.

Since the 1990s the Memory Clinic has used the GEDOC electronic database and biobank for clinical dementia. The database includes over 7000 patients and comprehensive longitudinal data for a duration of over 10 years. The database includes all patients referred to the Memory Clinic for the examination of CI. The various categories of data measures entered in the database offer excellent opportunities for multi-disciplinary research. Measures include medical, neuropsychological testing, clinical chemistry, genetic, neuroimaging (MRI, SPECT, PET) and EEG. The GEDOC database allows for advanced searches and statistical analyses. More recently, a GEDOC steering group has substantially improved various technical components of the database. Many publications and various doctoral theses have been produced using GEDOC.


Clinical Trials Unit, Memory Clinic, Karolinska University Hospital

Coordinator: Professor Miia Kivipelto

Phase I-III randomized controlled trials in subjects with prodromal AD or dementia, testing efficacy of potential disease-modifying treatment, including anti-amyloid drugs and nutraceuticals.


Co-STAR: Cortisol and Stress in Alzheimer’s disease.

Coordinator: Shireen Sindi (Co-Principal Investigator: Alina Solomon)

The overall aim of this project is to investigate stress-related factors, biomarkers and their associations with cognitive and daily life functioning in memory clinic patients. Specific aims are to: 1) Describe stress-related clinical profiles and biomarkers (including salivary cortisol levels) in relation to cognitive and daily life functioning in memory clinic patients; 2) Investigate the impact of baseline stress-related clinical and biomarker profiles together with other dementia-related genetic, CSF and MRI markers on the risk of developing cognitive decline/dementia during two years of follow-up; 3) Evaluate if stress-related clinical and biomarker profiles play similar roles in cognitive decline/dementia in memory clinic patients and the general population, and if lifestyle interventions to prevent cognitive decline/dementia improve stress-related clinical and biomarker profiles.

The project will focus on patients referred to the Memory Clinic at Karolinska University Hospital, Huddinge, who will be followed for two years. The ongoing FINGER population-based randomized trial to prevent cognitive decline will be used as population-based reference frame. Findings from this project can contribute to improving the care of older patients with cognitive problems by properly addressing stress-related factors, better estimating changes over time in patients’ cognitive and functional status and planning follow-up care accordingly. Moreover, findings from ongoing lifestyle intervention trials to prevent dementia can be adapted for clinical settings.


MIND-AD: Multimodal preventive trials for Alzheimer’s Disease: towards multinational strategies.

Principal investigator: Professor Miia Kivipelto
Scientific and clinical coordinators: Alina Solomon and Shireen Sindi

The goal of the MIND-AD project is to identify effective prevention strategies for AD/dementia tailored to different risk groups. The project is based on experiences and data from 5 ongoing European intervention studies on AD/dementia prevention, including FINGER (Finland), MAPT (France), PreDIVA (The Netherlands), LiPiDiDiet (Germany, Finland, The Netherlands, Sweden) and HATICE (Finland, France, The Netherlands, Sweden) studies. All these trials are testing the effects of multimodal interventions targeting vascular,dietary, and lifestyle-related risk factors in non-demented older adults.

The novel approach consists of multidomain interventions, inclusion of novel models of delivery (e.g. computer-based cognitive training, medical food), critical feedback from trial participants, and synergistic use of data from several European countries with over 10 000 participants. Further, a pilot study will be conducted, in which a multimodal preventive intervention will be tested for the first time in prodromal AD.

The project will generate guidelines for Pan-European multimodal preventive trials across the entire spectrum of the disease. Results from the MIND-AD project will also allow formulating practical recommendations for AD/dementia prevention in community and clinical settings (evidence-based immediate action). Given the current absence of curative treatments for AD, prevention represents the main tool to reduce the disease burden, and results from this project will support decisions about health education and community planning in Europe.
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EDPI: The European Dementia Prevention Initiative: an international collaboration within Europe, aiming to improve preventive strategies against dementia.

Coordinators: Miia Kivipelto and collaborators: Sandrine Andrieu and Edo Richard

The European Dementia Prevention Initiative brings together researchers involved in dementia prevention studies. It is an investigator-initiated initiative of several groups involved in ongoing dementia prevention trials in Europe. It started in 2011 with the first meeting held in Stockholm, Sweden. In addition to three ongoing randomised controlled dementia prevention trials in Europe, EDPI-collaborators recently managed to obtain funding from the European Union under the 7th Framework Program for a new dementia prevention study using an innovative internet-based intervention strategy, called HATICE (Healthy Ageing Through Internet Counselling in the Elderly).
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HATICE: Healthy Ageing Through Internet Counselling in the Elderly.

Coordinators: Miia Kivipelto and collaborators: Sandrine Andrieu and Edo Richard

HATICE is the first major research project following the launch of the European Dementia Prevention Initiative (EDPI) in 2011. Cardiovascular risk factors including hypertension, diabetes, obesity, smoking and lack of physical exercise are common in the elderly and increase the risk of myocardial infarction, stroke and dementia. The Main aims of HATICE are: 1) Develop an innovative, interactive internet intervention platform to optimise treatment of cardiovascular disease in the elderly, 2) Test this new intervention in a randomised controlled trial to investigate whether new cardiovascular disease and cognitive decline can be prevented.
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IMI-EPAD: The European Prevention of Alzheimer’s Dementia.

Coordinators: Miia Kivipelto is National Lead for Scandinavia

EPAD is an initiative launched by The Innovative Medicines Initiative (IMI), which is the largest public-private initiative in Europe. Its main goal is to accelerate the development of better and safer medications.
The European Prevention of Alzheimer’s Dementia (EPAD) project aims to develop an infrastructure that efficiently enables the undertaking of adaptive, multi-arm Proof of Concept studies for early and accurate decisions on the ongoing development of drug candidates or drug combinations. This includes evaluating patients’ reactions to a drug early in a clinical trial and modifying the trial according to these reactions. The EPAD project will initially run for five years.

The platform will draw European participants, whose records are already part of existing national/regional cohort or register studies, into an EPAD register of approximately 24,000 people. From this group, 6,000 people will be asked to join a pan-European EPAD Cohort for consistent, longitudinal follow-up, and approximately 1,500 of them will eventually be invited to enter the standing EPAD Proof of Concept Trial. This approach aims to ensure EPAD has access to an at-risk population showing biomarker evidence of Alzheimer’s disease prior to the development of dementia.

All data collected from the cohort and trial will become publically available for analysis to improve disease models in the pre-dementia phase of Alzheimers’ disease. This should lead to more accurate stratification for trial selection, improved measurements of outcomes and a greater understanding of Alzheimer’s disease processes before dementia develops. This project has numerous advantages over current approaches. These include: excellent pre-trial characterisation of subjects to inform selection and reduce screen failure; establishment of the highest possible quality Trial Delivery Centres (TDC’s) across Europe; rapid decision making on the likely success of a drug (or combination of drugs) in subsequent confirmatory trials and access to a shared placebo group.
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