Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures.

OBJECTIVE: White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify 'WM at risk', or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. METHODS: Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. RESULTS: CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. CONCLUSIONS: A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.

Factors associated with resistance to dementia despite high Alzheimer disease pathology.

BACKGROUND: Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. METHODS: A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. RESULTS: In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. CONCLUSION: Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

Brain volume loss in MCI predicts dementia.

Rates of temporal horn volume change were significantly greater in the subjects with mild cognitive impairment who were developing dementia vs those who remained stable.