Current and future uses of neuroimaging for cognitively impaired patients

Abstract

Technological advances have led to greater use of both structural and functional brain imaging to assist with the diagnosis of dementia for the increasing numbers of people with cognitive decline as they age. In current clinical practice, structural imaging (CT or MRI) is used to identify space-occupying lesions and stroke. Functional methods, such as PET scanning of glucose metabolism, could be used to differentiate Alzheimer's disease from frontotemporal dementia, which helps to guide clinicians in symptomatic treatment strategies. New neuroimaging methods that are currently being developed can measure specific neurotransmitter systems, amyloid plaque and tau tangle concentrations, and neuronal integrity and connectivity. Successful co-development of neuroimaging surrogate markers and preventive treatments might eventually lead to so-called brain-check scans for determining risk of cognitive decline, so that physicians can administer disease-modifying medications, vaccines, or other interventions to avoid future cognitive losses and to delay onset of disease.

Figure 1. Hypothetical course of the continuum of brain ageing

Neuroimaging is currently used once dementia develops. Future use is likely to involve detection of neurodegeneration before symptoms are obvious in preclinical stages such as normal ageing and MCI.

Figure 2. Neuropathological microscopic examination of the hippocampus after brain autopsy of a patient with AD, by use of immunohistochemical staining

Left: amyloid-β protein (length 1–42 amino acids; brown staining). Right: phosphorylated tau protein (brown staining).

Figure 3. Representative examples of brain [¹⁸F]FDG-PET images showing cognitive impairment

For each imaging method, the patient with MCI has intermediate values between the control and the patient with AD. Absolute scales are comparable within each patient with a specific probe, and warmer colours indicate higher values. In the patient with AD, the arrows point to frontal, parietal, and posterior cingulate (upper), frontal and temporal-parietal (middle), and medial temporal (lower) regions. Reproduced with permission from the National Academy of Sciences.

Figure 4. [¹¹C]PIB-standardised uptake images showing higher [¹¹C]PIB retention in a 79-year-old patient with AD than in a 67-year-old healthy control

Reproduced with permission from John Wiley and Sons, Inc.

Figure 5. Three-dimensional cortical surface projection images of [¹⁸F]FDDNP-PET scans from a control and a patient with AD

Lateral (upper) and medial (lower) brain surfaces are shown. Warmer colours indicate higher numbers of plaques and tangles.

Figure 6. MicroPET imaging of amyloid-β deposits in vivo with [¹⁸F]FDDNP in a triple transgenic amyloid-β rat model of AD

Transgenic rat model developed by Cephalon, Inc. (West Chester, PA) and Xenogen Biosciences (Cranbury, NJ). The 15-month-old animal showed the expected increase in binding in the cerebral cortex and hippocampus but not in white matter (left). Specificity of cortical [¹⁸F] binding was shown by blockage of the FDDNP signal (right) when the animal was rescanned after three 8 mg doses of naproxen (given over 2 days), which brought the [¹⁸F]FDDNP-binding signal to a value similar to that of a control animal.

Figure 7. Statistical parametric mapping of results of [¹⁸F]FDG-PET scanning

Shows a 5% decline in metabolic activity in the left dorsolateral prefrontal cortex after a 2-week programme of memory training, physical conditioning, relaxation exercises, and healthy diet, whereas no such decline was observed in the control group. The colour scale indicates the location of all cortical voxels that show significantly greater decline (p<0·01) in the intervention group compared with the control group. Left: left lateral viewpoint; right: from the top of the brain. The arrows point to the voxels of peak significance (p<0·001). Reproduced with permission from the American Association for Geriatric Psychiatry.