Monday, October 8, 2012

The earliest pathological changes in the brains of AD

    The earliest pathological changes in the brains of AD patients occur in the medial temporal lobe. The entorhinal cortex and its perforant pathway projections to the hippocampus are among the earliest brain regions to exhibit the neuropathological hallmarks of AD (Braak & Braak, 1996). The resulting loss of neurons and synapses in this region is manifested at a macroscopic level by medial temporal lobe atrophy, which can be observed by visual inspection of the brain at autopsy or by MRI in living patients.

    Paralleling the neuropathological changes, clinical symptoms of AD often involve cognitive impairments and fluctuations in body weight that are closely linked to medial temporal lobe atrophy (Grundman, Corey-Bloom, Jernigan, Archibald, & Thai, 1996a). In recent years, considerable effort has been devoted to imaging these structures to see if they serve as a useful adjunct in diagnosing and following patients with early AD.
    Previous work demonstrates that MRI-based quantitative measurements of the hippocampal formation are useful in differentiating patients with AD from normal control participants (Jack, Petersen, Xu, et al., 1997).
They found that the best discriminator between AD patients and normal controls was the hippocampal volume when different medial temporal lobe structures were compared. Participants with mild AD had mean hippocampal volumes that were approximately two standard deviations below the control mean.

   Volumetric measurements of the hippocampal formation may also be useful for predicting future conversion to AD in MCI participants. Jack, Petersen, Xu, et al. (1999) measured MRI-based hippocampal volume in
80 consecutive patients who met criteria for the diagnosis of MCI, and followed them longitudinally with approximately annual clinical and cognitive assessments. The primary endpoint was the crossover of individual MCI patients to a clinical diagnosis of AD during follow-up.

    During the period of observation, which averaged 33 months, 27 of 80 MCI patients developed dementia. Hippocampal atrophy at baseline was significantly associated with subsequent conversion from MCI to AD. The risk of AD was 50% within 3 years in MCI patients with moderate hippocampal atrophy; however, it was only 26% in patients with mild hippocampal atrophy (approximately 50% reduction in risk of conversion based solely on differences
in hippocampal volume). In MCI patients with normal hippocampal volume, the risk of developing AD dropped even further, with only 9% crossing over to AD within 3 years.

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