A loss of activity in areas of the brain that typically fire up when our brains are at rest may prove to be an accurate diagnostic marker for the earliest stages of Alzheimer's disease, according to a study published March 15 in the online edition of PNAS.
The search for reliable, noninvasive tests for incipient Alzheimer's disease continues apace. For example, researchers at Tokyo University unveiled a new candidate tracer for in-vivo imaging of amyloid in the brain in a recently published animal study (Okamura et al., 2004). Simultaneously, other approaches are also being taken to image the early effects of AD pathology on the brain.
Among the more robust findings in brain imaging of AD patients is reduced activity in the posterior cingulate cortex (PCC). Though not an area that develops early plaques or tangles, it is closely connected to medial temporal lobe areas such as hippocampus and entorhinal cortex, which do show AD pathology early in the process. Michael Greicius and his colleagues at Stanford University in Palo Alto, California, have noted that the PCC is also part of what Marcus Raichle of Washington University, St. Louis, and his colleagues have referred to as the "default mode" brain network (Raichle et al., 2001)—brain areas that are most active when the brain is not challenged by mental tasks or sensory stimulation. When mental activity is called for, these areas become less active or inactive in brain imaging studies.
As described in their current article, Greicius and colleagues postulated that activity in the default-mode network, particularly the PCC, might be attenuated in early AD as pathologic changes in the medial temporal lobe impair PCC function. In an initial set of analyses of healthy young subjects, the researchers made the discovery that the hippocampus also is active during rest, perhaps is even a part of the default-mode network. This leads the authors to suggest that the default-mode network may play a role in episodic memory processing.
When the researchers compared fMRI brain activity in 13 elderly subjects with mild AD and 13 age-matched normal controls, they found that resting-state activity was significantly reduced in the PCC and hippocampus of AD patients. This finding may have clinical implications, as the authors report that their method "distinguishes individual AD subjects from healthy elderly subjects with a sensitivity of 85 percent and a specificity of 77 percent." These values approach the range considered clinically relevant (see, for example, Trojanowski and Growdon, 1998). There are several obvious ways that the method might be refined, the authors note, raising hope that this type of imaging study could become a reliable predictor of which individuals are likely to develop AD.—Hakon Heimer
- Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82. PubMed.
- Trojanowski JQ, Growdon JH. A new consensus report on biomarkers for the early antemortem diagnosis of Alzheimer disease: current status, relevance to drug discovery, and recommendations for future research. J Neuropathol Exp Neurol. 1998 Jun;57(6):643-4. PubMed.
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- Okamura N, Suemoto T, Shimadzu H, Suzuki M, Shiomitsu T, Akatsu H, Yamamoto T, Staufenbiel M, Yanai K, Arai H, Sasaki H, Kudo Y, Sawada T. Styrylbenzoxazole derivatives for in vivo imaging of amyloid plaques in the brain. J Neurosci. 2004 Mar 10;24(10):2535-41. PubMed.
- Greicius MD, Srivastava G, Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42. PubMed.