Preventing dementia by preventing stroke: The Berlin Manifesto

Abstract

The incidence of stroke and dementia are diverging across the world, rising for those in low-and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood Hachinski et al.

Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage

“…The importance of the BBB as a therapeutic target is increasingly recognized and several anti-inflammatory or antioxidant drugs and novel molecules were identified as BBB protective on culture models [25] and introduced in the therapy of disease like stroke, amyotrophic lateral sclerosis and epilepsy [15][16][17]. We demonstrated that simvastatin protected brain endothelial cells in the Fig.…”

“…Taking into account the central role of the BBB in central nervous system (CNS) physiology [12] and neuropathologies [13] the cerebral vasculature emerges as a therapeutic target for neurological diseases [14,15]. Vascular inflammation and oxidative stress are central pathways in many CNS diseases such as stroke, amyotrophic lateral sclerosis and epilepsy, and anti-inflammatory or antioxidant drugs are also used to treat them [15][16][17]. For the present study we selected three clinically used drugs, the anti-inflammatory simvastatin and dexamethasone, and the free radical scavenger edaravone.…”

Poststroke Cognitive Impairment in Model-Based Economic Evaluation: A Systematic Review

“…Cognitive impairment (CI) and dementia are frequent consequences of stroke [1,2], and both are associated with reduced quality of life and increased resource use. Dementia is recognized as a significant international public health challenge [3], and stroke management and prevention have been identified as a key pathway for dementia prevention [4]. The potential benefits of management and prevention, for outcomes and costs, can only be fully captured in model-based economic evaluation by incorporating cognitive outcomes.…”

Prävention von Schlaganfall und Demenz in der Hausarztpraxis: Evaluation des Projektes INVADE

“…Die Ähnlichkeiten im Risikoprofil von Schlaganfällen und Demenzen legen eine gemeinsame Prävention nahe, wie sie kürzlich von der World Stroke Organization als "Berlin-Manifest" proklamiert wurde [15]. Ein solches Präventionsvorhaben ist mit dem Projekt INVADE (INterventionsprojekt VAskuläre Hirnerkrankungen und Demenz im Landkreis Ebersberg) seit längerer Zeit im Gang.…”