Regional cerebral blood flow assessed with 99mTc-ECD SPET as a marker of progression of mild cognitive impairment to Alzheimer's disease

Abstract

Patients diagnosed with mild cognitive impairment (MCI) have a higher risk of developing Alzheimer's disease (AD). However, not all such patients develop this kind of dementia. The purpose of this prospective study was to assess whether regional cerebral blood flow (rCBF) patterns measured with technetium-99m ethyl cysteinate dimer single-photon emission tomography ((99m)Tc-ECD SPET) in patients suffering from MCI are useful in predicting progression to AD. The study group comprised 42 patients who fulfilled MCI criteria according to the International Psychogeriatric Association and the Alzheimer's Disease Cooperative Study. rCBF was calculated in 16 regions of interest (ROIs). All patients were clinically assessed for 1-3 years. Twenty-one developed AD (group I) while the initial diagnosis of MCI was retained in the other 21 (group II). ROC curves were designed, and sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were determined for each ROI. Compared with group II (MCI), group I (AD) showed a significant reduction of relative blood flow (RBF), ranging from 7% to 10%, in the following areas: right and left prefrontal, right and left frontal, right and left parietal, right and left temporal, right and left frontoparietotemporal and left posterior lateral temporal. Left prefrontal, left frontal and left parietal areas showed sensitivities and specificities higher than 75% and areas below the ROC curve close to 80%. This study shows that RBF patterns in the right and left prefrontal, right and left frontal and left parietal areas are sensitive early markers of progression towards AD. Reduction of rCBF in the medial temporal and anterior lateral temporal cortex has no value as a predictor since it also occurs in patients with MCI who remain stable.

Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease

“…From a methodological point of view, the predictive accuracy of cortical rCBF obtained with the present 133 Xe method was very similar to previously reported SPECT studies [6,[18][19][20]. In fact, the reported areas under the ROC curves for the power of SPECT to predict AD in MCI populations show a range between 74 to 82 % [7,12,[19][20][21], which is quite similar to the 78 % we found for parietal rCBF in the present study. As methodological differences between studies may contribute to the variation in predictive accuracies, further studies are needed to evaluate if a combination of CSF biomarkers with other brain imaging methods will result in even better diagnostic risk assessment.…”

Event-related functional magnetic resonance imaging investigation of executive control in very old individuals with mild cognitive impairment

“…For greater levels of conflict, such as those experienced during both the preparation and decision phase of the task after the red cue, the cognitive demands might have exceeded the MCI's compensatory reserve, thus yielding a next to null load-related response in dlPFC. The weak response of dlPFC to the load of the task observed in MCI may reflect frontal lobe neural degeneration (Encinas et al 2003;Nagahama et al 2003) in MCI.…”

“…Neuroimaging studies of early Alzheimer Disease (AD) have shown increased prefrontal and parietal activity in patients compared with older controls executing a variety of executive cognitive tasks (Woodard et al 1998;Backman et al 1999;Saykin et al 1999;Bookheimer et al 2000;Corbetta et al 2000;Thulborn et al 2000;Grady et al 2003). Neuropsychological evidence of impaired Executive Cognitive Function (ECF) (Ready et al 2003) and evidence of disturbed metabolism (Piert et al 1996), blood flow (Encinas et al 2003) and functional connectivity (Elgh et al 2003) in neocortical systems subserving ECF in early AD patients, suggests that ECF impairment may precede Alzheimer Disease (Royall et al 2002;Baddeley et al 2001). Posterior parietal cortex (PPC), dorsolateral prefrontal cortex (dlPFC) and Anterior Cingulate Cortex (ACC) are key areas for the implementation of attentional control during the execution of ECF tasks (Royall et al 2002;Milham et al 2002).…”

Donepezil delays progression to AD in MCI subjects with depressive symptoms

“…Early therapeutic intervention in high-risk MCI subjects may potentially delay or even prevent the onset of dementia. Approaches incorporating neuropsychological testing, 4,5 structural and functional neuroimaging, [6][7][8] and CSF biomarkers 9 have demonstrated varying degrees of success in predicting which subjects with MCI will subsequently progress to AD.…”