Diffusion-weighted imaging (DWI) is a powerful new magnetic resonance imaging technique for evaluating tissue pathophysiology in vivo. We performed DWI in three orthogonal spatial directions in 10 patients with mild to moderate Alzheimer’s disease (AD) and 11 control subjects. Average apparent diffusion coefficients (ADCavg) were calculated for gray matter regions, and anisotropy indexes were calculated for white matter regions. Global measures of atrophy and white matter hyperintensities (WMH) were obtained on T₂-weighted images to control for their potential confounding effects on ADCavg and anisotropy. The measures of atrophy and WMH differed between the groups and were used as covariates in the subsequent statistical analyses. Patients with AD demonstrated diminished anisotropy in the posterior white matter (p < 0.0001) and increased ADCavg in the hippocampus (p < 0.05) when compared to the control group. Diffusion measures did not correlate with the severity of dementia. DWI provides a unique, quantitative parameter that may be sensitive to the pathophysiological and/or microstructural abnormalities that occur in AD.

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Alzheimer's disease (AD), the most common cause of dementia, has become a major public health concern as our population ages. In recent years, AD has attracted the attention of a wide range of biological disciplines, and substantial progress has been made in understanding the mechanisms of neurodegeneration in AD. Four different genes have now been associated with AD and are providing insights into the pathogenesis of the disease. The roles of beta-amyloid, tau, hormonal changes, inflammation, and oxidative stress in the neurodegeneration of AD are also being delineated. Based on these discoveries, rational therapeutic strategies are developing rapidly. The authors review these and other recent advances in the neurobiology and pharmacotherapy of AD.

We performed functional MRI using the echo-planar imaging and signal targeting with alternating radio frequency (EPISTAR) technique in 11 patients with Alzheimer's disease (AD) and 8 age-matched control subjects. Seven of the AD patients had qualitatively apparent focal areas of hypoperfusion in the posterior temporoparietal-occipital regions. At the earliest inversion time producing cortical enhancement, the ratios of parieto-occipital and temporo-occipital to whole slice signal intensity were significantly lower in the AD patients than in the controls. Parieto-occipital hypoperfusion correlated with dementia severity as measured by the Blessed Dementia Scale. EPISTAR may prove to be a rapid, noninvasive alternative to other functional neuroimaging modalities in the evaluation of patients with dementia.

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