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institutionalization can substantially reduce the financial impact of impaired elderly on society. Early diagnosis also provides patients with the opportunity to take an active role in planning for their futures and may enable them to participate in clinical trials. Accurate identification of individuals in


early stages of AD is of critical importance for the development of effective disease- modifying treatments. Inclusion of individuals who do not suffer from prodromal AD will decrease the power of a clinical trial and can reduce the likelihood of detecting a significant beneficial effect if a treatment actually slows the disease process. Prior clinical trials have observed lower than expected conversion rates to AD, which may have contributed to negative results. The ability to selectively enroll individuals who have AD pathology and are likely to develop dementia within the period of the trial if left untreated will increase the power to detect a treatment effect. We showed that selectively enrolling MCI patients with evidence of AD atrophy on a screening MRI (as shown in figure 1) would allow for a 57% reduction in sample size relative to a trial that used standard MCI inclusion criteria. This could substantially lower the cost of a trial and spur more research into potential therapies for this dreaded disease.

 Figure 3: Survival curves according to risk category for CSF biomarkers of A 42 and the tau/A 1-42 ratio (top row), for medial temporal lobe atrophy and the combination of atrophy and CSF risk factors (bottom row). Cox proportional hazard models controlled for age. The x- axis shows months to conversion to AD; the y-axis shows proportion of subjects who have not converted to AD. High risk is shown in red, low risk in blue for the individual CSF and atrophy measures. For the combined CSF and atrophy risk groups, survival curves for those testing negative for both risk factors are shown in green; those testing positive for both are shown in red. Blue and purple lines show that risk is elevated for individuals who test positive on one of these biomarkers but not the other, although risk is much higher when both biomarkers are present. When both are absent, risk of developing dementia within 3 years is low. Figure is modified from that presented in Heister, Brewer, Magda, Blennow, McEvoy, for the Alzheimer’s Disease Neuroimaging Initiative (2011). Predicting MCI outcome with clinically available MRI and CSF biomarkers. Neurology, In Press


CONCLUSION With the ageing of our population, a growing number of individuals are at risk of developing MCI and AD. Identification of individuals suffering from AD at early stages, prior to the development of dementia, can help ensure that individuals receive optimal clinical care to delay need for institutionalization. Early detection will be vital for risk/benefit assessments if disease- modifying therapies become available. This will ensure that individuals who suffer from AD receive treatment at an early enough stage to preserve cognitive abilities while preventing those who are at low risk of developing dementia from being unnecessarily exposed to risks of side effects. With its demonstrated sensitivity to AD neurodegeneration, and its ability to predict decline to dementia, quantitative structural MRI is likely to play and increasingly important role in clinical evaluation of individuals with memory complaints. ■


 REFERENCES References available on request (

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