Advertisement

Dementia: new vistas and opportunities

  • Vladimir HachinskiEmail author
Original Article

Abstract

Over the past four decades, Alzheimer disease has become near synonymous with dementia and the amyloid/tau hypothesis as its dominant explanation. However, this monorail approach to etiology has failed to yield a single disease-modifying drug. Part of the explanation stems from the fact that most dementias in the elderly result from interactive Alzheimer and cerebrovascular pathologies. Stroke and dementia share the same risk factors and their control is associated with a decrease in stroke and some dementias. Additionally, intensive control of risk factors and enhancement of protective factors improve cognition. Moreover, anticoagulation of atrial fibrillation patients decreases their chance of developing dementia by 48%. Preliminary data suggest that treating blood pressure to a target of 120 mmHg systolic compared to a target of 140 mmHg decreases the chances of mild cognitive impairment by 19%. The Berlin Manifesto establishes the scientific bases of “preventing dementia by preventing stroke.” Enlarging our vista of dementia to include cerebrovascular disease offers the opportunity of preventing not only stroke, but some dementias, beginning now.

Keywords

Stroke Alzheimer disease Cerebrovascular disease Prevention 

Notes

Acknowledgements

This article is based on a lecture delivered at the XLIX Congresso Societa Italian di Neurologia. Rome, Italy, October 27, 2018.

Compliance with ethical standards

Conflict of interest

The author declare that there is no conflict of interest.

Research involving human participants and/or animals

No human or animals were involved.

Informed consent

Not applicable. This is not a study.

References

  1. 1.
    The Global Burden of Disease Study 2017 (2018) Lancet 392:10159Google Scholar
  2. 2.
    Alladi S, Hachinski V (2018) World dementia: one approach does not fit all. Neurology 91:264–270CrossRefGoogle Scholar
  3. 3.
    Jin YP, Di Legge S, Ostbye T, Feightner JW, Hachinski V (2006) The reciprocal risks of stroke and cognitive impairment in an elderly population. Alzheimers Dement 6:171–178CrossRefGoogle Scholar
  4. 4.
    Kuzma E, Lourida I, Moore SF, Levine DA, Ukoumunne OC, Llewellyn DJ (2018) Stroke and dementia risk: a systematic and meta-analysis. Alzheimers Dement 14:1416–1428CrossRefGoogle Scholar
  5. 5.
    Solomon A, Mangialasche F, Richard E, Andrieu S, Bennett DA, Breteler MM, Fratiglioni L, Hooshmand B, Khachaturian AS, Schneider LS, Skoog I, Kivipelto M (2014) Advances in the prevention of Alzheimer’s disease and dementia. J Intern Med 275:229–250CrossRefGoogle Scholar
  6. 6.
    Rodrigue KM, Rieck JR, Kennedy KM, Devous MD Sr, Diaz-Arrastia R, Park DC (2013) Risk factors for β-amyloid deposition in healthy aging vascular and genetic effects. JAMA Neurol 70:600–606CrossRefGoogle Scholar
  7. 7.
    Nation DA, Edland SD, Bondi MW, Salmon DP, Delano-Wood L, Peskind ER, Quinn JF, Galasko DR (2013) Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults. Neurol 81:2024–2027CrossRefGoogle Scholar
  8. 8.
    Hughes TM, Kuller LH, Barinas-Mitchell EJM, McDade EM, Klunk WE, Cohen AD, Mathis CA, DeKosky ST, Price JC, Lopez OL (2014) Arterial stiffness and β-amyloid progression in nondemented elderly adults. JAMA Neurol 71:562–568CrossRefGoogle Scholar
  9. 9.
    Hooshmand B, Polvikoski T, Kivipelto M, Tanskanen M, Myllykangas L, Erkinjunttin T, Mäkelä M, Oinas M et al (2013) Alzheimer and cerebrovascular pathology: a population-based autopsy study. Brain 136:2707–271610CrossRefGoogle Scholar
  10. 10.
    Feigin VL (2016) Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol 15:913–924CrossRefGoogle Scholar
  11. 11.
    O’Donnell MJ, Xavier D, Liu L et al (2010) Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet 376:112–123CrossRefGoogle Scholar
  12. 12.
    Chen H, Kwong JC, Copes R, Tu K, Villeneuve PJ, van Donkelaar A, Hystad P, Martin RV, Murray BJ, Jessiman B, Wilton AS, Kopp A, Burnett RT (2017) Living near major roads and the incidence of dementia, Parkinson’s disease, and multiple sclerosis: a population-based cohort study. Lancet 389:718–726CrossRefGoogle Scholar
  13. 13.
    Livingston G, Sommerlad A. Orgeta V. Costafreda SG, Huntley J, Ames D, Ballard C et al (2017) Dementia prevention, intervention and care. The Lancet Commissions. LancetGoogle Scholar
  14. 14.
    Barnes DE, Byers AL, Gardner RC, Seal KH, Boscardin WJ, Yaffe K (2018) Association of mild traumatic brain injury with and without loss of consciousness with dementia in US military veterans. JAMA Neurol 75:1055–1061CrossRefGoogle Scholar
  15. 15.
    Azarpazhooh MR, Avan A, Cipriano LE, Munoz DG, Sposato LA, Hachinski V (2018) Concomitant vascular and neurodegenerative pathologies double the risk of dementia. Alzheimers Dement 14:148–156CrossRefGoogle Scholar
  16. 16.
    Vermeer SE, Prins ND, Heijer TD, Hofman A, Koudstaal PJ, Breteler MMB (2003) Silent brain infarcts and the risk of dementia and cognitive decline. NEJM 348:1215–1222CrossRefGoogle Scholar
  17. 17.
    Hachinski VC, Bowler JV (1993) Vascular dementia. Neurology 43:2159–2160CrossRefGoogle Scholar
  18. 18.
    Hachinski V (2019) Dementia: a radical rethink. Alzheimers Dement in pressGoogle Scholar
  19. 19.
    Moroney JT, Bagiella E, Desmond DW, Hachinski VC, Mölsä PK, Gustafson L, Brun A, Fischer P, Erkinjuntti T, Rosen W, Paik MC, Tatemichi TK (1997) Meta-analysis of the Hachinski ischemic score in pathologically verified dementias. Neurology 49:1096–1105CrossRefGoogle Scholar
  20. 20.
    Hachinski V, Oveisgharan S, Romney AK, Shankle WR (2012) Optimizing the Hachinski ischemic scale. Arch Neurol 69:169–175CrossRefGoogle Scholar
  21. 21.
    Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M, STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1) (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Lancet Neurol 12:822–838CrossRefGoogle Scholar
  22. 22.
    Thiel A, Cechetto DF, Heiss W-D, Hachinski V, Whitehead SN (2014) Amyloid burden, neuroinflammation, and links to cognitive decline after ischemic stroke. Stroke 45:2825–2829CrossRefGoogle Scholar
  23. 23.
    Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli D et al (2006) National Institute of Neurological Disorders and Stroke–Canadian stroke network vascular cognitive impairment harmonization standards. Stroke 37:2220–2241CrossRefGoogle Scholar
  24. 24.
    Samieri C, Perier M-C, Gaye B, Proust-Lima C, Helmer C, Dartigues J-F, Berr C, Tzourio C, Empana J-P (2018) Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA 320:657–664CrossRefGoogle Scholar
  25. 25.
    Kapral MK, Fang J, Silver FL, Hall R, Stamplecoski M, O’Callaghan CTJV (2013) Effect of a provincial system of stroke care delivery on stroke care and outcomes. CMAJ 185:E483–E491lCrossRefGoogle Scholar
  26. 26.
    Webster F, Saposnik G, Kapral M, Fung J, O'Callaghan C, Hachinski V (2011) Organized outpatient care: Stroke prevention clinical referrals are associated with reduced mortality after transient ischemic attack and ischemic stroke. Stroke 42:3176–3182CrossRefGoogle Scholar
  27. 27.
    Savva GM, Stephan BCM, the Alzheimer’s Society Vascular Dementia Systematic Review Group (2010) Epidemiological studies of the effect of stroke on incident dementia. A Systematic Review. Stroke 41:e41–e46Google Scholar
  28. 28.
    Sposato LA, Kapral MK, Wu J, Gill SS, Hackam DG, Cipriano LE, Hachinski V (2015) Declining incidence of stroke and dementia: coincidence or prevention opportunity? JAMA Neurol 72:1529–1531CrossRefGoogle Scholar
  29. 29.
    Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M (2015) 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 385:2255–2263CrossRefGoogle Scholar
  30. 30.
    Friberg L, Rosenqvist M (2018) Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J 39:453–460CrossRefGoogle Scholar
  31. 31.
    Koizumi K, Hattori Y, Ahn SJ, Buendia I, Ciacciarelli A, Uekawa K, Wang G, Hiller A, Zhao L, Voss HU, Paul SM, Schaffer C, Park L, Iadecola C (2018) Apoε4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function. Nat Commun 9:3816CrossRefGoogle Scholar
  32. 32.
    Hachinski V, World Stroke Organization (2015) Proclamation updated world stroke day proclamation. Stroke and potentially preventable dementias. Stroke 46:3039–3040CrossRefGoogle Scholar
  33. 33.
    Hachinski V, Ganten D, Lackland D, Kreutz R, Tsioufis K, Hacke W, on behalf of the World Stroke Organization, the World Heart Federation, the World Hypertension League and the European Society of Hypertension (2018) Implementing the proclamation of stroke and potentially preventable dementias. Int J Stroke 13:780–786CrossRefGoogle Scholar
  34. 34.
    Hachinski V (2018) Treatable and potentially preventable dementias. Cambridge University Press, United KingdomCrossRefGoogle Scholar

Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Department of Clinical Neurological SciencesWestern UniversityLondonCanada

Personalised recommendations