Alzheimer’s Disease International. World Alzheimer Report 2015: The Global Impact Of Dementia (ADI, 2015).
Jellinger, K. A. & Attems, J. Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol. 119, 421–433 (2010).
Schneider, J. A., Wilson, R. S., Bienias, J. L., Evans, D. A. & Bennett, D. A. Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology 62, 1148–1155 (2004).
Solomon, A. et al. Advances in the prevention of Alzheimer’s disease and dementia. J. Intern. Med. 275, 229–250 (2014).
McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 263–269 (2011).
Dubois, B. et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 13, 614–629 (2014).
Skrobot, O. A. et al. Progress toward standardized diagnosis of vascular cognitive impairment: guidelines from the Vascular Impairment of Cognition Classification Consensus Study. Alzheimers Dement. 14, 280–292 (2018).
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Publishing, Arlington, VA, 2013).
Norton, S., Matthews, F. E., Barnes, D. E., Yaffe, K. & Brayne, C. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. 13, 788–794 (2014).
Wu, Y. T. et al. The changing prevalence and incidence of dementia over time - current evidence. Nat. Rev. Neurol. 13, 327–339 (2017).
Chan, K. Y. et al. Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990-2010: a systematic review and analysis. Lancet 381, 2016–2023 (2013).
WHO MONICA Project Principal Investigators. The World Health Organization MONICA project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. J. Clin. Epidemiol. 41, 105–114 (1988).
Mangialasche, F., Ngandu, T. & Kivipelto, M. in Oxford Textbook of Geriatric Medicine. 3rd edn (eds Michel, J.-P., Beattie, B., Martin, F. & Walston, J.) (Oxford Univ. Press, Oxford, 2017).
Deckers, K. et al. Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Int. J. Geriatr. Psychiatry 30, 234–246 (2014).
Kivimaki, M. et al. Body mass index and risk of dementia: analysis of individual-level data from 1.3 million individuals. Alzheimers Dement. 14, 601–609 (2017).
Power, B. D. et al. Body adiposity in later life and the incidence of dementia: the health in men study. PLOS ONE 6, e17902 (2011).
Tolppanen, A. M., Solomon, A., Soininen, H. & Kivipelto, M. Midlife vascular risk factors and Alzheimer’s disease: evidence from epidemiological studies. J. Alzheimers Dis. 32, 531–540 (2012).
Rouch, L. et al. Antihypertensive drugs, prevention of cognitive decline and dementia: a systematic review of observational studies, randomized controlled trials and meta-analyses, with discussion of potential mechanisms. CNS Drugs 29, 113–130 (2015).
Blondell, S. J., Hammersley-Mather, R. & Veerman, J. L. Does physical activity prevent cognitive decline and dementia?: A systematic review and meta-analysis of longitudinal studies. BMC Public Health 14, 510 (2014).
Fratiglioni, L., Paillard-Borg, S. & Winblad, B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol. 3, 343–353 (2004).
Carvalho, A., Rea, I. M., Parimon, T. & Cusack, B. J. Physical activity and cognitive function in individuals over 60 years of age: a systematic review. Clin. Interv. Aging 9, 661–682 (2014).
Tolppanen, A. M. et al. Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia. Alzheimers Dement. 11, 434–443 (2015).
Brown, B. M. et al. Intense physical activity is associated with cognitive performance in the elderly. Transl Psychiatry 2, e191 (2012).
Ngandu, T. et al. Education and dementia: what lies behind the association? Neurology 69, 1442–1450 (2007).
Kuiper, J. S. et al. Social relationships and risk of dementia: a systematic review and meta-analysis of longitudinal cohort studies. Ageing Res. Rev. 22, 39–57 (2015).
Wilson, R. S., Segawa, E., Boyle, P. A. & Bennett, D. A. Influence of late-life cognitive activity on cognitive health. Neurology 78, 1123–1129 (2012).
Marioni, R. E. et al. Social activity, cognitive decline and dementia risk: a 20-year prospective cohort study. BMC Public Health 15, 1089 (2015).
Coley, N., Vaurs, C. & Andrieu, S. Nutrition and cognition in aging adults. Clin. Geriatr. Med. 31, 453–464 (2015).
Lourida, I. et al. Mediterranean diet, cognitive function, and dementia: a systematic review. Epidemiology 24, 479–489 (2013).
Morris, M. C. et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 11, 1007–1014 (2015).
Martinez-Lapiscina, E. H. et al. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J. Neurol. Neurosurg. Psychiatry 84, 1318–1325 (2013).
Smith, P. J. et al. Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension 55, 1331–1338 (2010).
Mannikko, R. et al. The Nordic diet and cognition — the DR’s EXTRA study. Br. J. Nutr. 114, 231–239 (2015).
Cataldo, J. K., Prochaska, J. J. & Glantz, S. A. Cigarette smoking is a risk factor for Alzheimer’s Disease: an analysis controlling for tobacco industry affiliation. J. Alzheimers Dis. 19, 465–480 (2010).
Anttila, T. et al. Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study. BMJ 329, 539 (2004).
Fratiglioni, L. & Qiu, C. in Oxford Textbook of Old Age Psychiatry (eds Dening, T. & Thomas, A.) 389–414 (Oxford Univ. Press, Oxford, 2013).
Rovio, S. et al. The effect of midlife physical activity on structural brain changes in the elderly. Neurobiol. Aging 31, 1927–1936 (2010).
Komulainen, P. et al. BDNF is a novel marker of cognitive function in ageing women: the DR’s EXTRA Study. Neurobiol. Learn. Mem. 90, 596–603 (2008).
Erickson, K. I. et al. Exercise training increases size of hippocampus and improves memory. Proc. Natl Acad. Sci. USA 108, 3017–3022 (2011).
Liu, Y. et al. Education increases reserve against Alzheimer’s disease—evidence from structural MRI analysis. Neuroradiology 54, 929–938 (2012).
Brayne, C. et al. Education, the brain and dementia: neuroprotection or compensation? Brain 133, 2210–2216 (2010).
Zahr, N. M., Kaufman, K. L. & Harper, C. G. Clinical and pathological features of alcohol-related brain damage. Nat. Rev. Neurol. 7, 284–294 (2011).
Zhao, J., Stockwell, T., Roemer, A., Naimi, T. & Chikritzhs, T. Alcohol consumption and mortality from coronary heart disease: an updated meta-analysis of cohort studies. J. Stud Alcohol Drugs 78, 375–386 (2017).
Kivipelto, M. et al. Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. J. Cell. Mol. Med. 12, 2762–2771 (2008).
Strand, B. H. et al. Interaction of apolipoprotein E genotypes, lifestyle factors and future risk of dementia-related mortality: the cohort of Norway (CONOR). Dement. Geriatr. Cogn. Disord. 40, 137–147 (2015).
Wang, H. X. et al. Education halves the risk of dementia due to apolipoprotein epsilon4 allele: a collaborative study from the Swedish brain power initiative. Neurobiol. Aging 33, e1–e7 (2012).
Zhong, G., Wang, Y., Zhang, Y., Guo, J. J. & Zhao, Y. Smoking is associated with an increased risk of dementia: a meta-analysis of prospective cohort studies with investigation of potential effect modifiers. PLOS ONE 10, e0118333 (2015).
Hassing, L. B. et al. Overweight in midlife and risk of dementia: a 40-year follow-up study. Int. J. Obes. 33, 893–898 (2009).
Imtiaz, B., Tolppanen, A. M., Kivipelto, M. & Soininen, H. Future directions in Alzheimer’s disease from risk factors to prevention. Biochem. Pharmacol. 88, 661–670 (2014).
Qiu, C. & Fratiglioni, L. A major role for cardiovascular burden in age-related cognitive decline. Nat. Rev. Cardiol. 12, 267–277 (2015).
Solomon, A. & Soininen, H. Dementia: risk prediction models in dementia prevention. Nat. Rev. Neurol. 11, 375–377 (2015).
Tang, E. Y. et al. Current developments in dementia risk prediction modelling: an updated systematic review. PLOS ONE 10, e0136181 (2015).
Stephan, B. C., Kurth, T., Matthews, F. E., Brayne, C. & Dufouil, C. Dementia risk prediction in the population: are screening models accurate? Nat. Rev. Neurol. 6, 318–326 (2010).
Kivipelto, M. et al. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol. 5, 735–741 (2006).
Sindi, S. et al. The CAIDE dementia risk score app: the development of an evidence-based mobile application to predict the risk of dementia. Alzheimers Dement. 1, 328–333 (2015).
O’Donnell, C. A. et al. Reducing dementia risk by targeting modifiable risk factors in mid-life: study protocol for the Innovative Midlife Intervention for Dementia Deterrence (In-MINDD) randomised controlled feasibility trial. Pilot Feasibility Stud. 1, 40 (2015).
Anstey, K. J. et al. A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: the ANU-ADRI. PLOS ONE 9, e86141 (2014).
Andrieu, S., Coley, N., Lovestone, S., Aisen, P. S. & Vellas, B. Prevention of sporadic Alzheimer’s disease: lessons learned from clinical trials and future directions. Lancet Neurol. 14, 926–944 (2015).
Dangour, A. D. et al. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am. J. Clin. Nutr. 91, 1725–1732 (2010).
Sink, K. M. et al. Effect of a 24-month physical activity intervention versus health education on cognitive outcomes in sedentary older adults: the LIFE randomized trial. JAMA 314, 781–790 (2015).
Barha, C. K., Davis, J. C., Falck, R. S., Nagamatsu, L. S. & Liu-Ambrose, T. Sex differences in exercise efficacy to improve cognition: a systematic review and meta-analysis of randomized controlled trials in older humans. Front. Neuroendocrinol. 46, 71–85 (2017).
Young, J., Angevaren, M., Rusted, J. & Tabet, N. Aerobic exercise to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst. Rev. 4, CD005381 (2015).
Ball, K. et al. Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA 288, 2271–2281 (2002).
Unverzagt, F. W. et al. ACTIVE cognitive training and rates of incident dementia. J. Int. Neuropsychol. Soc. 18, 669–677 (2012).
Wolinsky, F. D., Vander Weg, M. W., Howren, M. B., Jones, M. P. & Dotson, M. M. A randomized controlled trial of cognitive training using a visual speed of processing intervention in middle aged and older adults. PLOS ONE 8, e61624 (2013).
Hill, N. T. et al. Computerized cognitive training in older adults with mild cognitive impairment or dementia: a systematic review and meta-analysis. Am. J. Psychiatry 174, 329–340 (2017).
Chiu, H. L. et al. The effect of cognitive-based training for the healthy older people: a meta-analysis of randomized controlled trials. PLOS ONE 12, e0176742 (2017).
Martin, M., Clare, L., Altgassen, A. M., Cameron, M. H. & Zehnder, F. Cognition-based interventions for healthy older people and people with mild cognitive impairment. Cochrane Database Syst. Rev. 1, CD006220 (2011).
Kelly, S., Olanrewaju, O., Cowan, A., Brayne, C. & Lafortune, L. Interventions to prevent and reduce excessive alcohol consumption in older people: a systematic review and meta-analysis. Age Ageing 47, 175–184 (2017).
Kivipelto, M. et al. The Finnish geriatric intervention study to prevent cognitive impairment and disability (FINGER): study design and progress. Alzheimers Dement. 9, 657–665 (2013).
Ngandu, T. et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 385, 2255–2263 (2015).
Rosenberg, A. et al. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: the FINGER trial. Alzheimers Dement. 14, 263–270 (2018).
Solomon, A. et al. Effect of the apolipoprotein e genotype on cognitive change during a multidomain lifestyle intervention: a subgroup analysis of a randomized clinical trial. JAMA Neurol. 75, 462–470 (2017).
Vellas, B. et al. MAPT study: a multidomain approach for preventing Alzheimer’s disease: design and baseline data. J. Prev. Alzheimers Dis. 1, 13–22 (2014).
Gillette-Guyonnet, S. et al. Commentary on “A roadmap for the prevention of dementia II. Leon Thal Symposium 2008.” The Multidomain Alzheimer Preventive Trial (MAPT): a new approach to the prevention of Alzheimer’s disease. Alzheimers Dement. 5, 114–121 (2009).
Andrieu, S. et al. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol. 16, 377–389 (2017).
Moll van Charante, E. P. et al. Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial. Lancet 388, 797–805 (2016).
Diamond, K. et al. Randomized controlled trial of a healthy brain ageing cognitive training program: effects on memory, mood, and sleep. J. Alzheimers Dis. 44, 1181–1191 (2015).
Lee, K. S. et al. Effects of a multidomain lifestyle modification on cognitive function in older adults: an eighteen-month community-based cluster randomized controlled trial. Psychother. Psychosom. 83, 270–278 (2014).
Matz, K. et al. Multidomain lifestyle interventions for the prevention of cognitive decline after ischemic stroke: randomized trial. Stroke 46, 2874–2880 (2015).
Ihle-Hansen, H. et al. Multifactorial vascular risk factor intervention to prevent cognitive impairment after stroke and TIA: a 12-month randomized controlled trial. Int. J. Stroke 9, 932–938 (2014).
Barnes, D. E. et al. The Mental Activity and eXercise (MAX) trial: a randomized controlled trial to enhance cognitive function in older adults. JAMA Intern. Med. 173, 797–804 (2013).
Soininen, H. et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer’s disease (LipiDiDiet): a randomised, double-blind, controlled trial. Lancet Neurol. 16, 965–975 (2017).
SPRINT Research Group et al. A randomized trial of intensive versus standard blood-pressure control. N. Engl. J. Med. 373, 2103–2116 (2015).
Alzheimer’s Association. Study shows intensive blood pressure control reduces risk of mild cogn'itive impairment (MCI) and the combined risk of MCI and dementia. AA https://www.alz.org/aaic/downloads2018/Wed-am-briefing-developing-topics.pdf (2018).
Barbera, M. et al. Designing an internet-based multidomain intervention for the prevention of cardiovascular disease and cognitive impairment in older adults: the HATICE trial. J. Alzheimers Dis. 62, 649–663 (2018).
Richard, E. et al. Healthy ageing through internet counselling in the elderly: the HATICE randomised controlled trial for the prevention of cardiovascular disease and cognitive impairment. BMJ Open 6, e010806 (2016).
Kivipelto, M., Mangialasche, F. & Ngandu, T. World wide fingers will advance dementia prevention. Lancet Neurol. 17, 27 (2017).
Pointing the way to primary prevention of dementia (Editorial). Lancet Neurol. 16, 677 (2017).
Kulmala, J., Ngandu, T. & Kivipelto, M. Prevention matters: time for global action and effective implementation. J. Alzheimers Dis. 64 (Suppl. 1), S191–S198 (2018).
Richard, E. et al. Methodological challenges in designing dementia prevention trials — the European Dementia Prevention Initiative (EDPI). J. Neurol. Sci. 322, 64–70 (2012).
Brookmeyer, R., Gray, S. & Kawas, C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am. J. Publ. Health 88, 1337–1342 (1998).
Vellas, B., Andrieu, S., Sampaio, C., Coley, N. & Wilcock, G. Endpoints for trials in Alzheimer’s disease: a European task force consensus. Lancet Neurol. 7, 436–450 (2008).
Harrison, J. et al. A neuropsychological test battery for use in Alzheimer disease clinical trials. Arch. Neurol. 64, 1323–1329 (2007).
Smith, A. D., Mangialasche, F. & Kivipelto, M. Dementia research priorities — 2. Lancet Neurol. 16, 181–182 (2017).
Shah, H. et al. Research priorities to reduce the global burden of dementia by 2025. Lancet Neurol. 15, 1285–1294 (2016).
Beckett, N. S. et al. Treatment of hypertension in patients 80 years of age or older. N. Engl. J. Med. 358, 1887–1898 (2008).
Williamson, J. D. et al. Intensive versus standard blood pressure control and cardiovascular disease outcomes in adults aged >/ = 75 years: a randomized clinical trial. JAMA 315, 2673–2682 (2016).
Strandberg, T. E. et al. Health-related quality of life in a multidomain intervention trial to prevent cognitive decline (FINGER). Eur. Ger. Med. 8, 164–167 (2017).
Marengoni, A. et al. The effect of a 2-year intervention consisting of diet, physical exercise, cognitive training, and monitoring of vascular risk on chronic morbidity-the FINGER randomized controlled trial. J. Am. Med. Dir. Assoc. 19, 355–360 (2018).
Willis, S. L. et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA 296, 2805–2814 (2006).
Rebok, G. W. et al. Ten-year effects of the advanced cognitive training for independent and vital elderly cognitive training trial on cognition and everyday functioning in older adults. J. Am. Geriatr. Soc. 62, 16–24 (2014).