Positron emission tomography scans obtained for the evaluation of cognitive dysfunction

Abstract

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism, with devastating neuropathologic, clinical, social, and economic consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are performed with (18)F-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility for clinicians evaluating patients with cognitive impairment and in distinguishing among primary neurodegenerative disorders and other etiologies contributing to cognitive decline. In addition to focusing on the effects on cerebral metabolism examined with (18)F-fluorodeoxyglucose PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact on the enormous human toll exacted by these diseases.

Figure 1. Longitudinal visual and quantitative PET evaluations of an initially clinically “normal” subject with Mild Decline in Cognition (MDC)

First three columns of images represent transaxial slices through the brain, displayed from superior (parietal cortex posteriorly) to inferior (temporal cortex posteriorly) levels. Right side of image is left side of brain. PET data are displayed in an inverse linear gray scale (left color bar underneath brain images). In the fourth column, color denotes standardized volumes of interest quantifying FDG activity in parietotemporal cortex (2-dimensional color scale underneath brain images; y-axis denotes number of standard deviations (SD), x-axis denotes magnitude of difference from asymptomatic controls.) (Top) FDG PET scan of high-functioning 71 year old male, who noted mild decline in his own cognition, but was considered “normal” both by general clinical evaluation and formal neuropsychologic testing. Scan reveals mild metabolic asymmetry with left temporal cortex (arrow in rightmost plane) lower than right. Left parietotemporal cortex was quantified as 3 SD and 9% below normal. Posterior cingulate cortex was also quantified as falling 3 SD below normal (not shown) at this point, and scan was interpreted as concerning for incipient dementia process. (Middle) Progression of posterior hypometabolism (arrows in middle and right planes). Left parietotemporal cortex was quantified as 4 SD and 12% below normal. Patient now met criteria for “mild cognitive impairment” (MCI) on formal neuropsychologic testing (Bottom) Further progression of posterior hypometabolism (arrows in left, middle, and right planes). Left parietotemporal cortex was quantified as 5 SD and 16% below normal. Patient now met criteria for borderline MCI/dementia.

Figure 2. Baseline metabolic comparison of clinically normal subjects who showed declining cognition versus cognitive stability over the subsequent two years

A 3-dimensional MR-based mapping technique of coregistered PET data applied to 19 clinically normal subjects to compare baseline metabolism among those whose neuropsychologic testing demonstrated significant decline (n=4) over the subsequent two years, versus those who remained stable (n=15). Larger differences are represented as higher on the rainbow scale. Decliners had relative hypometabolism in entorhinal, parahippocampal, parietal, temporal, and posterior cingulate cortical areas at baseline.

Figure 3. Changes in cortical metabolism typical for various degrees of impairment, from normal to late AD

FDG PET images of transaxial planes from five patients, shown at comparable axial levels. (First row) Normal pattern, provided for reference. Note how posterior cingulate cortex (arrow) normally has activity that is visibly higher than in average cortex. (Second row) Patient with Age Associated Memory Impairment, not meeting criteria for MCI. Arrow denotes a patchiness in the inferior parietal cortex that is beginning to emerge, and activity in posterior cingulate cortex is also seen to be less robust than in normal subject. (Third row) Mild Cognitive Impairment, nearing conversion to Alzheimer's disease, with clear hypometabolism of parietal, parietotemporal and posterior cingulate cortex. (Fourth row) Early Alzheimer's disease, demonstrating posterior-predominant cortical hypometabolism. (Fifth row) Late Alzheimer's disease, with both prefrontal, parietal, temporal, and posterior cingulate cortical regions markedly hypometabolic, but with continued relative preservation of sensorimotor and visual cortex. At lower planes than shown here, basal ganglia, thalamus, cerebellum and brainstem would also be seen to be relatively preserved at all stages.

Figure 4. Dementia with Lewy bodies

FDG PET pattern is typically posterior-predominant, as in AD, but without preferential sparing of occipital cortex.

Figure 5. Vascular dementia

Patient was diagnosed both clinically and by structural imaging with vascular dementia. Arrows on this scan indicate hypometabolism of the right parietal cortex (left), right basal ganglia and thalamus (middle) and right temporal cortex (right). The hypometabolism of the left cerebellum (right) is characteristic of cross-cerebellar diaschisis, caused by diminished afferent input from contralateral cortex.