Neuroimaging in Alzheimer’s Disease

Neuroimaging in Alzheimer’s Disease

Hidenao Fukuyama (Kyoto University Graduate School of Medicine, Japan)
Copyright: © 2013 |Pages: 5
DOI: 10.4018/978-1-4666-3604-0.ch023
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The diagnosis of Alzheimer’s disease (AD) is often based on clinical and pathological data. Positron emission tomography (PET) using the tracer 18F-FDG revealed findings specific to AD-mainly the posterior part of the brain and the association cortices of the parietal and occipital lobes were affected by a reduction in glucose metabolism. Recent advances in the development of tracers for amyloid protein, which is the key protein in the pathogenesis of AD, enables the pattern of deposition of amyloid protein in the brain to be visualized. Various tracers have been introduced to visualize other aspects of AD pathology. Recent clinical interests on dementia have focused on the early detection of AD and variation of Parkinson’s disease, namely dementia with Lewy body disease (DLB), because the earlier the diagnosis, the better the prognosis. The differential diagnosis of mild AD or mild cognitive impairment (MCI) as well as DLB has been studied using PET and MRI as part of the NIH’s Alzheimer disease Neuroimaging initiative (ADNI). At present, many countries are participating in the ADNI, which is yielding promising results. This chapter’s study will improve the development of new drugs for the treatment of dementia patients by enabling the evaluation of the effect and efficacy of those drugs.
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Pet And Spect Imaging

Fluorine-18 Labeled Deoxyglucose (FDG)-PET

In the early 1980’s, FDG-PET was applied to neuro-degenerative disorders to clarify the energy metabolism of the brain. AD showed a typical reduction in glucose metabolism by FDG-PET as well as in cerebral blood flow (CBF) and oxygen metabolism in the posterior association cortices (Fukuyama, Ogawa, Yamauchi, Yamaguchi, Kimura, Yonekura & Konishi, 1994). Statistical analysis demonstrated the reduction of metabolism and CBF in the posterior cingulated cortex and precuneus (Minoshima, Frey, Koeppe, Foster & Kuhl, 1995). This finding is also specific to the early phase of AD, which involved mild cognitive impairment (MCI) of the amnestic type. These observations have been confirmed by single photon emission CT (SPECT) and FDG-PET, and they were clearly shown using statistical image manipulations, such as 3D-SSP (Figure 1) or SPM.

Figure 1.

CBF reduction in statistical images. The parietal and temporal lobes as well as the posterior cigulate cortex and precunes showed reduced CBF. These images were taken from statistical parametric mapping (Friston, Frith, Liddle&Frackowiak, 1991) and 3D-SSP (Minoshima, Frey, Koeppe, Foster&Kuhl, 1995). The use of these findings on SPECT CBF or FDG-PET makes the diagnosis of AD and MCI easy. The arrow indicates the posterior cigulate cortex and precuneus.


Based on this background work, AD can be diagnosed easily using PET or SPECT combined with clinical and psychological data. Because the functional state of the brain is damaged in several specific regions, this particular pattern of damage supports the correct diagnosis. These types of image analyses have been used in clinical trials for the early diagnosis on AD in studies performed all over the world.


New Tracers For Ad Diagnosis

C11-Labeled PK11195 Imaging for Microglial Activation

McGeer et al. proposed that a mild inflammatory process was involved in the pathology of AD (Lee, Sparatore, Del Soldato, McGeer & McGeer, 2009). Their hypothesis was based upon the observation that the incidence of AD is relatively small in patients with rheumatoid arthritis who are administered aspirin compared with its frequency in the normal population and the pathology caused by activated microglial reactions in the affected brain. Based on that proposal, R. Banati attempted to visualize the activated microglia by PK11195 in AD patients (Figure 2) (Cagnin, Brooks, Kennedy, Gunn, Myers, Turkheimer, Jones & Banati, 2001).

Figure 2.

PK11195 image of AD patient


The left temporal lobe is affected by the accumulation of tracer, showing left temporal lobe damage (Courtesy of Dr. Richard Banati, Hammersmith Hospital, London, UK).

Although the cause and pathophysiological implications of this mild inflammatory process remain unresolved, amyloid deposition and Alzheimer fibrillary tangle formation might be related to this pathology.

The role of inflammation with regard to pathogenesis of AD remains unclear. Activated microglia have been shown in the degenerative lesions, which are affected by slowly progressive tissue necrosis. In some cases, degenerative lesions can be cleared up by an unknown physiological process to maintain the tissue in its normal state. Whether this observation represents a pathological process that aggravates the plaque and tangle formation or simply a reactive process in degenerative tissues remains to be determined.

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