1	White Matter Hyperintensities Are Related to the Severity of Medial Temporal Atrophy- A Biomarker of Neurodegenerative Disease
2	Introduction White matter hyperintensities (WMH) are bright foci on T2-weighted MRI scans WMH occur among elderly cognitively normal subjects and in those with MCI and a variety of dementias, including Alzheimer’s disease. WMH may also result in Neurodegeneration or associated processes, such as gliosis, microglial infiltration and inflammation. WMH are often non-specific and have been described in asymptomatic patients.
3	Pathophysiology of AD AD often begins in the medial temporal structures The severity of AD is proportional to the degree of atrophy in these structures (especially the hippocampus and entorhinal cortex). Medial temporal atrophy (MTA) can be identified on magnetic resonance images (MRI) MTA correlates with the severity of Alzheimer’s disease (AD)
4	Our Study We Adapted a previously developed Visual Rating System (VRS) to rate WMHs in the periventricular and centrum semiovale regions of the brain. We Examined the ability of VRS-WMH ratings to distinguish between no cognitive impairment (NCI), nonamnestic mild cognitive impairment (na-MCI), amnestic MCI (a-MCI), and Probable AD
5	Technique 192 subjects All received: (1) full clinical history; (2) neurological evaluation; (3) Mini-Mental State Evaluation (MMSE); (4) neuropsychological test battery MRI scans were obtained on a 1.5 Tesla machine 3-D MP-RAGE (Siemens), or 3-D SPGR (General Electric) sequences were obtained to acquire contiguous coronal slices Fluid Attenuated Inversion Recovery (FLAIR) sequences were obtained for WMH assessment
6	VRS for WMH Evaluate WMHs on FLAIR sequences in four periventricular (PV-WMHs; frontal, parietal, occipital, temporal) regions, and the centrum semiovale (CSO-WMHs) region. Based on a “0” to “4” severity scale. Criteria for PV-WMHs ratings were based on extension of WMHs from the lateral ventricle to the cerebral cortex 0 = none detectable 1 = thin rim of hyperintensity adjacent to the ventricle 2 = extension of WMHs to 1/3 the distance to the cerebral cortex 3 = extension of WMHs to 2/3 the distance to the cerebral cortex 4 = extension of WMHs to the cerebral cortex.
7	WMHs and Visual Ratings: bilateral Periventricular Frontal Regions
8	WMHs and Visual Ratings: bilateral Periventricular Frontal Regions
9	WMHs and Visual Ratings: Bilateral Periventricular Occiptal Regions VRS Score = 4 Occipital Horns
10	VRS for WMH Criteria for CSO-WMHs were based on the anterior-posterior extent of WMHs in the CSO 0 = no CSO-WMHs 1 = at least 1 CSO-WMHs ≤ 1 cm in greatest dimension 2 = at least 1 CSO-WMHs > 1 cm in dimension 3 = multiple coalescing CSO- occupying < 2/3 AP-CSO 4 = multiple coalescing CSO- occupying > 2/3 AP-CSO
11	WMHs and Visual Ratings: Centrum Semiovale (CSO) regions
12	WMHs and Visual Ratings: Centrum Semiovale (CSO) regions
13	White Matter Hyperintensity (WMHs) Scores for Each Diagnostic Group Study
14	Results Probable AD subjects had higher average WMH scores in all brain regions relative to NCI subjects Probable AD subjects had higher WMH scores in all regions, relative to non-amnestic MCI subjects Probable AD subjects had higher mean WMH scores than amnestic MCI subjects In the left centrum semiovale, however they did not differ with respect to WMH scores in other brain regions
15	Results Subjects with probable AD had higher average MTA scores in comparison to subjects in other diagnostic groups. Probable AD subjects were differentiated from na-MCI and MCI subjects based on total WMH scores, but did not differ from subjects with a-MCI.
16	Conclusion This Visual Rating System (VRS) may be utilized for evaluation for periventricular and centrum semiovale white matter hyperintensities. The VRS rating directly correlates with the severity of dementia along a gradient from NCI to probable AD.