A new iron sensitive MR sequence (susceptibility weighted imaging -SWI) enabling the simultaneous quantitation of regional brain iron levels and brain microbleeds (BMB) has been acquired serially to study dementia. Cohorts of mildly cognitively impaired (MCI) elderly (n=73) and cognitively normal participants (n=33) have been serially evaluated for up to 50 months. SWI phase values (putative iron levels) in 14 brain regions were measured and the number of brain microbleeds (BMB) were counted for each SWI study. SWI phase values showed a left putaminal mean increase of iron (decrease of phase values) over the study duration in 27 participants who progressed to dementia compared to Normals (p=0.035) and stable MCI (p=0.01). BMB were detected in 9 of 26 (38%) of MCI participants who progressed to dementia and are a significant risk factor for cognitive failure in MCI participants (risk ratio = 2.06 (95% confidence interval 1.37-3.12)). SWI is useful to measure regional iron changes and presence of BMB, both of which may be important MR based biomarkers for neurodegenerative diseases.

The majority of mild cognitive impairment (MCI) studies use baseline and one follow-up measurement to determine the clinical course of the disorder. This report of MCI clinical course is based on the a statistical evaluation of multiple neurocognitive tests over a 60 month period in elderly normal and MCI cohorts. The data includes serial informant-based measures (Clinical Dementia Rating [CDR]) and a comprehensive battery of neuropsychological tests analyzed by two different regression methods. Twenty-nine elderly participants entered the study as neurocognitively normal; 26 remained normal, 2 progressed to MCI, and 1 progressed to dementia. Eighty-three participants entered the study as multiple domain MCI cases; 10 became normal, 46 remained MCI, and 27 progressed to dementia. Three of the 27 demented died with full necropsies performed (one case was progressive supranuclear palsy and two confirmed Alzheimer’s disease with severe cerebral amyloid angiopathy (CAA)). Without serial measures, 1 in 8 MCI could be misclassified as “stable MCI” despite reverting to normal. The stable MCI cohorts did not benefit from practice effects though the normal subjects did. Applying Classification and Regression Tree (CART) analysis enabled prediction of the endpoint status of participants from baseline values with 78.6% accuracy. The fluctuating cognitive status of the multiple domain MCI cases implies a remitting pathologic process with elements of recovery consistent with a progressive microvasculopathy such as CAA.

An 88-year-old woman with a clinical diagnosis of Alzheimer's disease and advanced dementia, was evaluated with standard MRI of the brain as well as Susceptibility Weighted Imaging (SWI) with the MRI. SWI revealed more extensive brain microhemorrhages than standard MRI techniques, allowing the radiologic diagnosis of cerebral amyloid angiopathy. SWI shows promise as a more sensitive diagnostic tool than standard brain MRI for the evaluation of patients with dementia.

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