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Feature Alzheimer’s DiseAse

as 69%. These results, shown in figure 1, demonstrate the potential of quantitative structural MRI to provide useful information for individual patient prognosis.

TRANSLATION TO CLINICAL PRACTICE Although there is a large body of research showing that quantitative structural MRI is sensitive to the progressive neurodegeneration associated with AD, to be of use in clinical practice, standardized image acquisition and image processing methods are needed to provide reliable, automated, patient-specific measures of regional brain atrophy. Recent years have witnessed the development of a number of large-scale, multi-site longitudinal studies of AD biomarkers worldwide, and these studies have contributed to the standardization of image acquisition protocols that are robust to inter-site variation and that provide the high degree of contrast between brain grey and

 Standardized image acquisition and image processing methods are needed to provide reliable, automated, patient-specific measures of regional brain atrophy

white matter that is required for use of automated image analysis algorithms. Image analysis software, NeuroQuantTM

(CorTechs Labs Inc, La Jolla, CA), has been developed that provides reliable, fully automated quantification of brain structures affected in AD. Volumetric measures provided by this software have been validated against manual segmentation and the software has received approval from the Federal Drug Administration (FDA) in the USA for clinical use. The clinical output report (see figure 2) compares an individual patient’s regional brain volumes with those of a normative database, correcting for gender, head size, and age. We recently used this software to quantify medial temporal lobe atrophy in 192 MCI participants of the Alzheimer’s Disease Neuroimaging Initiative, and compared the ability of this atrophy measure to predict development of dementia with the predictive

Imaging & Diagnostics Issue 4 2011 39

ability of CSF biomarkers, which are also commercially available. The results showed that individuals testing positive for either atrophy or CSF biomarkers developed dementia at a much faster rate those testing negative, with equivalent predictive ability between the MRI measure and the best CSF measure (the ratio of tau to Ab42

): hazard ratios were 3.9 [95%

confidence interval 2.3-6.2] and 4.1 [2.1-8.0] respectively. Combining information across MRI and CSF measures substantially improved predictive ability. Individuals who tested negative for both biomarkers were at very low risk of developing dementia – only 10% of these individuals developed AD over the next three years, versus 80% of those testing positive on both biomarkers (hazard ratio of 13.8 [5.0 – 38.5] when both biomarkers were positive, see figure 3). These results show that commercially available MRI and CSF methods can be used to significantly improve predictive prognosis in MCI.

IMPORTANCE OF EARLY DIAGNOSIS Although there are no treatments to prevent or cure AD, early diagnosis is important for ensuring optimal care. Cognitive impairment in older patients can arise from a number of causes, some of which may be reversible, such as sleep disorders, anxiety, depression, medication side effects, vitamin deficiency, or thyroid disease. Accurate identification of the underlying cause is necessary to determine the appropriate treatment. If evidence points to AD as the underlying etiology, early diagnosis can ensure patients and caregivers are provided appropriate information and support, and patients are prescribed symptomatic medications. Although this will not alter the course of the disease, adequate support and symptomatic treatment may aid in maintaining cognitive function and reducing caregiver stress, which can lead to a delay in institutionalization. Even a one-year delay in 

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