Dementia has been declared a public health priority by the World Health Organization (WHO), which has also prioritized research into dementia prevention. Prevention is pivotal in managing the dementia epidemic globally, and the sharing of data is vital to informing this process. World Wide FINGERS will facilitate the use of data from several countries, creating a unique opportunity for rapid knowledge dissemination and implementation.

ABOUT

The FINGER trial is the first randomized controlled trial showing that it is possible to prevent cognitive decline using a multi-domain lifestyle intervention among older at-risk individuals. The results highlighted the value of addressing multiple dementia risk factors as a strategy to protect brain health, and promote overall health and functioning.

Three European countries have completed pioneering multi-domain prevention trials (RCTs) in community-dwelling seniors: the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER); the French Multidomain Alzheimer Preventive Trial (MAPT); the Dutch Prevention of Dementia by Intensive Vascular Care (PreDIVA). The experiences and results from these studies allow the identification of key methodological issues underlying the successful delivery of cost-effective preventive interventions.

Prevention of cognitive impairment requires integrated approaches targeting risk factors shared by chronic disorders common in older age, the definition of accessible and sustainable strategies for populations with different geographical, economic and cultural settings.

The FINGER trial is the first large, long-term RCT indicating that a multi-domain intervention with exercise, diet, cognitive and social stimulation and management of vascular/metabolic risk factors may benefit cognition in subjects at risk of dementia. FINGER represents a pragmatic model, currently tested in diverse settings, including the U.S., through the Alzheimer’s Association U.S. POINTER study.

Projects

FINGER:

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (FINLAND)
FINGER is a 2-year multi-center randomized controlled trial (intervention study) carried out in Finland (Coordinated by the National Institute of Health and Welfare, Helsinki), 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 enrolled 1.260 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. To learn more, contact Miia Kivipelto or Tiia Ngandu.

Website: FINGER research project

U.S. POINTER:

The Alzheimer's Association U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk trial (USA)
World-renowned researchers, under the leadership of Drs. Laura Baker, Miia Kivipelto and Rachel Whitmer, in collaboration with the Alzheimer’s Association, are initiating efforts to replicate the results of the Finnish trial in the U.S. (to test the generalizability of the FINGER findings in American older adults). U.S. POINTER is a two-year clinical trial to evaluate whether lifestyle interventions that simultaneously target many risk factors protect cognitive function in older adults who are at increased risk for cognitive decline. U.S. POINTER is the first such study to be conducted in a large group of Americans across the United States. This is truly a once-in-a-lifetime opportunity for both participants and researchers. To learn more, contact Laura Baker or Rachel Whitmer or pointerinfo@alz.org.

Website: U.S. POINTER study

SINGER:

SINGapore intervention study to prevent cognitive impairment and disability (SINGER) initiative
The SINGapore intervention study to prevent cognitive impairment and disability (SINGER) initiative aims to initially develop pilot studies of culturally appropriate interventions based on FINGER so as to eventually undertake a large confirmatory study.There are challenges particularly for the dietary and cognitive interventions but novel approaches are required to address the challenge of preventing cognitive impairment in aging populations. To learn more, contact Christopher Chen.

MYB trial:

The Maximizing Technology and Methodology for Internet Prevention of Cognitive Decline: the Maintain Your Brain (MYB) trial (AUSTRALIA)
This randomized controlled trial addresses modifiable risk factors for dementia in general and AD in particular, physical inactivity, cognitive inactivity, depression, overweight and obesity, as well as diabetes (type 2), high blood pressure and smoking. The trial aims to determine the efficacy of a multimodal targeted internet intervention to reduce the rate of cognitive decline in non-demented, community-dwelling people aged 55-77 years and in the long-term to delay the onset of dementia. All assessments and interventions are conducted online. The four basic intervention modules are physical activity, computerized brain training, nutritional advice and cognitive behavior therapy for depression. Advice and helplines are provided regarding smoking cessation, reducing excess consumption of alcohol and controlling blood pressure and cholesterol. Brain training includes a socialization component starting with internet buddies. The first 2,300 participants have been randomized to date and another tranche of participants will be in the trial in mid-October. To learn more, contact Henry Brodaty or Megan Heffernan.

MIND-ADmini:

The Multimodal Preventive Trial for Alzheimer’s Disease (MIND-ADmini) (SWEDEN, FINLAND, FRANCE, GERMANY)
MIND-ADmini is an ongoing pilot trial testing the feasibility of the FINGER multidomain lifestyle intervention in people with prodromal Alzheimer’s disease. Participants are in the early stages of the disease and have mild memory problems, but not dementia. They also have some vascular or lifestyle-related risk factors.

Conducting a pilot trial in people who already have some Alzheimer’s disease symptoms is important because of the potential need for additional support with healthy lifestyle maintenance. The duration of the trial is 6 months, with an optional 6-month extension. Participants are randomized into 3 groups: multidomain lifestyle intervention based on the FINGER model; multidomain lifestyle intervention plus medical food; and standard care. The rationale for combining a multidomain intervention with medical food is recent evidence indicating synergistic effects between different intervention components (e.g. omega-3 fatty acids and physical activity). Nutrient deficiencies have also been described in prodromal Alzheimer’s disease, and medical food may be needed in addition to dietary guidance for optimal effect.

The main aims of MIND-ADmini are to evaluate the feasibility of and adherence to the multidomain intervention. Exploratory aims include intervention effects on changes in vascular and metabolic risk factors; depressive, anxiety and stress symptoms; health-related quality of life; physical performance; and blood biomarkers. There is also a qualitative interview study focusing specifically on the experiences of the trial participants.

Results will be used in the planning of future larger trials and may serve as a model for combining non-pharmacological and pharmacological interventions.

AU-ARROW

TThe AUstralian-Multidomain Approach to Reduce Dementia Risk by PrOtecting Brain Health with Lifestyle intervention (AU-ARROW) study (AUSTRALIA)
Ralph Martins is the lead investigator of the lifestyle arm of the Australian Imaging, Biomarker & Lifestyle Study of Ageing (AIBL) in Australia and an internationally renowned scientist in the field of dementia research. Martins will be leading a team of internationally recognized Australian researchers which include Kaarin Anstey and Sharon Naismith. This Australian team will collaborate closely with Laura Baker (U.S. POINTER) to commence an Australian version, namely, the AU-ARROW trial. The Australian team will also work closely with Miia Kivipelto, who undertook seminal work in the Finnish FINGER trial and Dr. Maria Carrillo from the Alzheimer's Association.

To reflect the Australian initiating efforts to align with the World Wide-FINGERS initiative for dementia prevention, the research team will facilitate the harmonization of methods used in the AU-ARROW study to that used in the U.S. POINTER study. Facilities include access to state of the art screening measures to identify those at highest risk of Alzheimer’s dementia and published lifestyle modification protocols including prevention strategies that can be readily utilized as part of this preventive program. The study is a 2-year multidomain lifestyle intervention program to evaluate its efficacy in the prevention of cognitive decline. This study is innovative, as it will be the first to include a comprehensive set of assessment markers and longitudinal 6- month follow-up after the intervention is completed to assess the degree to which benefits are sustained.

This Australian initiative is a unique opportunity for participants and researchers and is proposed to commence in mid-2019 in Perth, Western Australia, and Sydney, New South Wales. To learn more, contact Ralph Martins at ralph.martins@mq.edu.au, r.martins@ecu.edu.au.

MIND-CHINA

The Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND-CHINA) study (CHINA)
Inspired by the FINGER project, we launch the MIND-CHINA project, which is a single-center cluster randomized controlled study that is aimed at investigating whether multimodal interventions may help maintain cognitive and physical functioning among rural-dwelling older adults. The interventions target people who are aged 60-79 years and living in the rural communities of Yanlou Town in Yanggu County, Western Shandong province. We seek to explore the potential effects of two multimodal intervention programs, in which the Chinese rural tradition and sociocultural factors are carefully incorporated: (1) Multimodal Intervention-I: comprehensive management of three major cardiovascular risk factors (hypertension, diabetes and high cholesterol) and (2) Multimodal Intervention-II: management of major cardiovascular risk factors plus multimodal lifestyle intervention (smoking, physical exercise, social and mental activities, and nutritional guidelines). MIND-CHINA is being conducted by the Shandong Provincial Hospital Affiliated to Shandong University, led by Yifeng Du and coordinated by Yongxiang Wang in collaboration with senior researchers from Karolinska Institutet, Stockholm, Sweden (Chengxuan Qiu and Miia Kivipelto). MIND-CHINA is supported in part by a major grant from the National Key R&D Program of China Ministry of Science and Technology and a Sino-Sweden joint research project grant from the National Natural Science Foundation of China (NSFC) and the Swedish Research Council (VR). To learn more, please contact Yifeng Du, Yongxiang Wang or Chengxuan Qiu.

GOIZ-ZAINDU:

GOIZ-ZAINDU ("take care early" in Basque language), is a pilot, controlled, randomized, one-year multimodal interventional study launched in June 2018 to adapt the FINGER methodology to the cultural and social context of the Basque population and evaluate the feasibility of a multidomain lifestyle intervention program. The exploratory aim is to assess the efficacy of the intervention to reduce participants CAIDE risk scores and reduce cognitive decline. 200 participants living in Beasain, aged 60 or older, not diagnosed with dementia, with a CAIDE Dementia Risk Index score of 6 points or higher and a below-expected performance in at least one of three brief cognitive screening tests (AD8 questionnaire, Fototest, memory alteration test) will be included. All these participants have been previously identified through the GOIZ-ALZHEIMER-Beasain early detection of cognitive impairment program ongoing since January 2015. Participants in the intervention group will receive intensive management of vascular risk factors, nutritional advice to increase adherence to Mediterranean diet patterns and will follow a physical activity program and a personalized cognitive training program. Participants in the control group will receive standard of care attention from their primary care physicians and nurses. For more information contact Dr. Mikel Tainta or Dr. Pablo Martinez-Lage.

The GOIZ-ZAINDU project is carried out by the CITA-Alzheimer Foundation with support by the Department of Health-Osakidetza of the Basque Government.

Consortium

Finland

Miia Kivipelto, University of Eastern Finland
Tiia Ngandu, National Institute of Health and Welfare

USA

Laura Baker, Wake Forest School of Medicine
Rachel Whitmer, Kaiser Permanente Northern California Division of Research
Jeff Williamson, M.D., Wake Forest School of Medicine
Mark Espeland, Ph.D., Wake Forest School of Medicine
Kaycee Sink, M.D., Wake Forest School of Medicine
Rema Raman, Ph.D., Alzheimer’s Therapeutic Research Institute, University of Southern California

Sweden

Miia Kivipelto, Karolinska Institute
Shireen Sindi, Karolinska Institute
Alina Solomon, Karolinska Institute
Francesca Mangialasche, Karolinska Institute

Australia

Henry Brodaty, The University of New South Wales
Megan Heffernan, The University of New South Wales

Singapore

Christopher Chen, National University Health System