Can we prevent memory disorders? Experience from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)
Tiia Ngandu MD, PhD
Outline • Rational • Study design • Current status and some preliminary results • Future directions
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Occurrence of memory disorders • Prevalence increases with age 65-69 years 1.5% >85 years 35% >95 years up to 60% • 35.6 million people with dementia in 2010 115.4 million in 2050 (World Alzheimer Report 2009)
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AD is a multi-factorial disease: target several risk factors simultaneously for an optimal preventive effect RISK FACTORS Hypertension Dyslipidemia Obesity Vascular insults Unhealthy Diabetes diet Smoking Neuronal damage Alcohol misuse
APOE, Other genes
0
Late-life
Mid-life
Adult life 20
60
Physical activity
DEMENTIA
Transition 75
Cognitive and social activity
Brain reserve ?
Education PROTECTIVE FACTORS
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Why here? Why now? Long tradition in risk factor monitoring: The FINRISK Study Intervention studies: North Karelia Project, Diabetes Prevention Study, Dose-Responses to Exercise Training
FINRISK Aim: Integrate memory disorders into the existing framework
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Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability
Objective: To reduce cognitive impairment through a 2-year multi-domain life-style intervention Target population: 60-77 year old persons (n= 1200) from previous population-based non-intervention studies (FINRISK, D2D) Time schedule: Screening began in September 2009 and was completed in 2011. The intervention will be completed in the beginning of 2014
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Study design: A multi-center (6 sites), blinded, RCT enrolling 1200 persons randomized into 2 groups (multi-domain intervention or regular health advice) for a 2-year period. Extended follow-up to 7 years. Multidomain intervention: i) nutritional guidance ii) physical activity iii) cognitive training iv) intensive monitoring and management of vascular risk factors
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INCLUSION CRITERIA: persons at risk of dementia/ cognitive decline Dementia Risk score > 6 Based on risk factors assessed in earlier population surveys: Age, Education, Sex, SBP, Cholesterol, BMI, Physical Activity (Kivipelto et al., Lancet Neurology 2006)
AND Cognitive performance at the mean level or slightly lower than expected for age CERAD: 1) Word List Immediate Memory task (10 words x3) < 19 words AND/OR 2) Word List Delayed Recall < 75% AND/OR 3) MMSE < 26
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INTERVENTION SCHEDULE NUTRITIONAL GUIDANCE:
INTERVENTION KICK-OFF
RANDOMIZATION
7 group & 3 individual sessions
Baseline visit (NTB)
Screening (Nurse: CERAD; Physician)
Recruitment (Dementia risk score)
INTENSIVE INTERVENTION
PHYSICAL ACTIVITY: 2-3x/wk muscle strength & 5-6x/wk aerobic training
COGNITIVE TRAINING:
COGNITIVE TRAINING:
9 group sessions, Independent training 3x/wk 6mo
2 group sessions, Independent training 3x/wk 6mo
MANAGEMENT OF METABOLIC AND VASCULAR RISK FACTORS 6 nurse visits, 4 physician visits Follow-up visit
Follow-up visit
Month
MINIINTERVENTION
PHYSICAL ACTIVITY: 1-2x/wk muscle strength & 1-4x/wk aerobic training
3
6
9
Follow-up visit
12
Follow-up visit
15
Follow-up visit
18
21
24
Follow-up visit
REGULAR HEALTH ADVICE
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1) Nutritional guidance Based mainly on Finnish Nutrition Recommendations The dietary measures recommended: •Fish 2-3 portions/week, 1-2 portions being fatty fish •High consumption of fruits and vegetables •Whole grain in all cereal products •Low-fat options in milk and meat products •Vegetable margarine and rapeseed oil instead of butter •Decrease salt and sucrose intake •Keep alcohol consumption in moderation • Adjust the energy level of the diet if needed •Individually tailored counselling
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2) Exercise intervention: Progression of the resistance and aerobic training program
Resistance Exercise Exercise frequency/wk Duration of exercise, min Number of muscle groups Repetitions/ set Load % 1RM Number of sets Aerobic Exercise Exercise frequency/wk Duration of exercise, min
0-1 mo
1-3 mo
3-6 mo
6-24 mo
1-2 30-45 8-10 8-15 40-50 2
1-2 30-60 8-10 10-20 60 2-3
2 45-60 8-10 8-20 70 1-3
2-3 60 8-10 8-20 70-80 2-3
2 30-45
2-3 30-45
3-4 30-60
3-5 45-60
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FINGER intervention
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3) Cognitive training and social activity • Intervention implementation – 10 group sessions lead by study psychologist – Individual computer-based training (6 months x2) – Training targets episodic memory, executive function, mental speed, and working memory
• Social activity is increased throughout the study: – Study visits, group meetings – Arranged activities with local offices of the Finnish Alzheimer Society
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4) Monitoring and management of metabolic and vascular risk factors • Based on Finnish guidelines regarding prevention and treatment of hypertension, dyslipidemia, diabetes, obesity • Intervention implementation –Regular meetings with study nurse and physician (clinical assessments, lab results, motivation to lifestyle changes)
–Recommendation to contact own physician when initiation or adjustment of pharmacological treatment is necessary
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OUTCOMES Primary: • Cognitive impairment (Neuropsychological Test Battery, Trail Making & Stroop tests) Secondary: • Dementia (after 7 years) • Depressive symptoms (Zung scale) • Vascular risk factors, morbidity and mortality • Disability (questionnaire, ADL + IADL) • Quality of life (RAND-36, 15D) • Utilization of health resources • Blood markers (i.e. inflammation, redox status, lipid and glucose metabolism, NMR metabonomics)
• Brain MRI measures (n=100) and PET (n=90) 20/11/2012
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Safety Committee Monitoring Committee
FINLAND
PI: M. Kivipelto Coordination Group/THL:
Oulu cohort
Heads: T. Laatikainen, J.Lindström, M Peltonen Coordinator: T. Ngandu Field coordinator: J. Lehtisalo Data manager, Statistician, Administrator
T. Strandberg
Kuopio cohort
Supervision:
H.Soininen
Seinäjoki cohort
Nutrition: J. Lindström Exercise: R. Rauramaa, S.Pajala Cognitive&social activation: T.Hänninen, T.Ngandu Vascular factors: J. Tuomilehto, T.Strandberg, R. Antikainen
J. Tuomilehto
Turku cohort
Volunteer organizations Practices in the community
A. Jula
Helsinki cohort 20/11/2012 M. Kivipelto
Vantaa cohort T. LaatikainenFINGER / Tiia Ngandu
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Current status •5496 were invited (Sep 2009 – Nov 2011) •2654 (48 %) agreed to come for screening visit •1260 fulfilled inclusion criteria and were randomized
•1140 have completed 12 months and 700 have completed 24 months •Drop-out rate 10 % •Last evaluations in spring 2014
BL
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24mo
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Experience of the participants Very positive:
51 % of the intervention group 38 % control group
”I have friends who are jealous when they hear all that I
have been offered to do at this course” ”Right amount of everything” ”Nice experience” ”Coming here has always given me reinforcement and strength to take care of myself and others” (participant from the control group)
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RELEVANCE OF A MULTI-DOMAIN INTERVENTION Will test to what extent a multi-domain intervention may delay cognitive impairment and dementia onset in people at an increased risk Is an innovative approach to delay cognitive impairment while simultaneously intervening upon several risk factors of other major diseases Will provide data urgently needed for health education and community planning
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EDPI
European Dementia Prevention Initiative
• FINGER
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability
• preDIVA
Prevention of Dementia by Intensive Vascular Care
• MAPT
Multidomain Alzheimer Preventive Trial
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0
A 10–25% reduction in all seven risk factors could potentially prevent 1.1–3.0 million AD cases worldwide. July 2011 20/11/2012
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Acknowledgements Grant support: Academy of Finland, La Carita Foundation, Novo Nordisk Foundation, Alzheimer’s Research and Prevention Foundation, FAS, Alzheimer Association, Juho Vainio Foundation Hilkka Soininen Tuula Pirttilä † Rainer Rauramaa Raimo Sulkava Miia Kivipelto Alina Solomon Tiina Laatikainen Tuomo Hänninen Markku Peltonen Teemu Paajanen Jaana Lindström Antti Jula Jaakko Tuomilehto Satu Pajala Satu Ahtiluoto Timo Strandberg Jenni Lehtisalo Riitta Antikainen Liisa Saarikoski Pirjo Saastamoinen Lars Bäckman Marko Grönholm Francesca Mangialasche Esko Levälahti Bengt Winblad Päivi Valve Anna Stigsdotter Neely
Turku PET Centre 20/11/2012
FINGER / Tiia Ngandu
Juha Rinne 22
