Ugo Paolo Guerra

Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment

ObjectiveAim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI.Methods17 healthy subjects (age = 69 ± 3, 9 females), and 23 amnestic MCI patients (age = 70 ± 6, 10 females) underwent brain MR scan and 99mTc ECD SPECT. Conversion to AD was ascertained on average 19 ± 10 months after baseline: 9 had converted (age = 69 ± 3, 4 females), and 14 had not (age = 71 ± 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol.We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis.ResultsIn comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side.We found no overlap between significant atrophy and significant hypoperfusion regions.ConclusionsParahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.

Brain SPECT in subtypes of mild cognitive impairment Findings from the DESCRIPA multicenter study

The Development of Screening Guidelines and Clinical Criteria of Predementia Alzheimer’s Disease (DESCRIPA) multicenter study enrolled patients with MCI or subjective cognitive complaints (SUBJ), a part of whom underwent optional brain perfusion SPECT. These patients were classified as SUBJ (n = 23), nonamnestic MCI (naMCI; n = 17) and amnestic MCI (aMCI; n = 40) based on neuropsychology. Twenty healthy subjects formed the control (CTR) group. Volumetric regions of interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures, corrected for age and center, showed significant differences between groups (p = 0.01) and VROI (p < 0.0001) with a significant group-region interaction (p = 0.029). In the post hoc comparison, SUBJ did not differ from CTR. aMCI disclosed reduced uptake in the left hippocampus and bilateral temporal cortex (compared with CTR) or in the left hippocampus and bilateral parietal cortex (compared with SUBJ). In the naMCI group, reduced VROI values were found in the bilateral temporal cortex and right frontal cortex. In the comparison between aMCI and naMCI, the former had lower values in the left parietal cortex and precuneus. Discriminant analysis between SUBJ/CTR versus all MCI patients allowed correct allocations in 73 % of cases. Mean VROI values were highly correlated (p < 0.0001) with the learning measure of a verbal memory test, especially in the bilateral precunei and parietal cortex and in the left hippocampus. In a subset of 70 patients, mean VROI values showed a significant correlation (p < 0.05) with the white matter hyperintensities score on MRI. In conclusion, MCI subtypes have different perfusion patterns. The aMCI group exhibited a pattern that is typical of early Alzheimer’s disease, while the naMCI group showed a more anterior pattern of hypoperfusion. Instead, a homogeneous group effect was lacking in SUBJ.

SPECT Predictors of Cognitive Decline and Alzheimer's Disease in Mild Cognitive Impairment

Baseline brain single photon emission computed tomography (SPECT) was evaluated in eighty subjects with mild cognitive impairment (MCI) who were followed for a mean of about two years, when twelve patients developed Alzheimers disease (AD), nineteen showed memory decline (D), and forty-three had normal cognition assessment (stable: S) (six drop-out). Volumetric Regions of Interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures showed significant effects for both the group (S, D, and AD; p < 0.004) and VROI (p < 0.0001) factors, with significant group*region interaction (p < 0.01). At post-hoc comparison, hippocampal VROIs values were lower in AD than in D and S, while parietal VROIs values were lower in D and AD than in S. These four VROI significantly correlated with verbal delayed recall score at follow-up visit. Receiver operating characteristic (ROC) curves for the mean hippocampal VROI value showed 0.81 sensitivity with 0.86 specificity in separation of S+D from AD (p < 0.0001), and 0.69 sensitivity with 0.75 specificity in separation of S from D+AD (p < 0.0002). ROC curves for the mean parietal VROI value showed 0.62 sensitivity with 0.70 specificity in separation of S from D+AD (p < 0.0002). Baseline SPECT can support outcome prediction in subjects with MCI.

IQ SPECT Allows a Significant Reduction in Administered Dose and Acquisition Time for Myocardial Perfusion Imaging: Evidence from a Phantom Study

We recently demonstrated in a clinical trial the ability of a new protocol, IQ SPECT, to acquire myocardial perfusion imaging (MPI) studies in a quarter of the time (12 s/view) of the standard protocol, with preserved diagnostic accuracy. We now aim to establish the lower limit of radioactivity that can be administered to patients and the minimum acquisition time in SPECT MPI using an IQ SPECT protocol, while preserving diagnostic accuracy. Methods: An anthropomorphic cardiac phantom was used to acquire clinical rest scans with a simulated in vivo distribution of 99mTc-tetrofosmin at full dose (740 MBq) and at doses equal to 50%, 25%, and 18%. For each dose, 2 sets of images were acquired, with and without a transmural defect (TD). Variable acquisition times were also used for each dose. We analyzed raw data and reconstructed images, including no correction and correction for attenuation (AC), for scatter (SC), or for both (ACSC). Images were evaluated qualitatively and quantitatively in order to assess left ventricle (LV) wall thickness (full width at half maximum of the medial sections), TD, and cavity contrast in the LV wall. Data were compared across different acquisition times within the same dose and across doses with the same acquisition time. Results: Images were visually scored as very-good quality except those acquired with 4 s/view or less at 100% dose and 6 s/view or less with 50%, 25%, or 18% dose, due to false-positive defects. LV wall thickness was not significantly different among all acquisitions. Cavity contrast remained unchanged within the same dose for all images and tended to be higher in AC and ACSC images. TD contrast remained unchanged within the same dose for all images. In SC and no-correction images, contrast was constant for all doses. AC images had significantly higher TD contrast values, and ACSC images showed a drop in TD contrast for a 50% dose. Conclusion: IQ SPECT effectively preserved both image quality and quantitative measurements with reduced acquisition time or administered dose in a phantom study. These findings suggest that approximately one eighth of the time, compared with standard protocols with a full dose, or a lower dose at an acquisition time of 12 s/view can be applied in MPI without the loss of diagnostic accuracy.

Assessment of the incremental diagnostic value of florbetapir F 18 imaging in patients with cognitive impairment: The incremental diagnostic value of amyloid PET with [18F]-florbetapir (INDIA-FBP) study

Importance Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. Objective To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. Design, Setting, and Participants The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. Main Outcomes and Measures Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. Results Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). Conclusions and Relevance Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Functional compensation in incipient Alzheimer's disease

Aim of this study was to investigate the functional compensation mechanism in incipient Alzheimers disease (AD). Seventeen elderly healthy subjects and nine amnestic MCI patients with incipient AD underwent brain MR scan and 99mTc ECD SPECT. We processed all images with SPM2, we created t maps, showing the wholebrain GM atrophy and functional changes, and we properly masked them with each other in order to assess relatively preserved perfusion or depression. Incipient AD showed GM atrophy in the medial temporal and temporoparietal lobes, in the insula and in the retrosplenial cortex, and GM hypoperfusion in the medial temporal and temporoparietal lobes. Relatively preserved perfusion, we could hypothesize to be compensatory in the setting of neuronal loss, was found in the posterior cingulate, in the head of the hippocampus, in the amigdala, and in the insula bilaterally, while functional depression occurred in bilateral parahippocampal gyri. In AD, a perfusional compensatory mechanism takes place in the neocortex, while perfusional depression occurs in the medial temporal lobe. These results help understand the reactive phenomena induced by the brain to try and counteract the pathological changes of AD.

The Role of Neuroimaging in Evaluating Patients Affected by Creutzfeldt–Jakob Disease: A Systematic Review of the Literature

Diagnosis of Creutzfeldt–Jakob disease during life can be challenging since the huge variability of the symptoms which can be observed, especially in its early stages, may simulate other common forms of dementia. In latest years, noninvasive techniques such as magnetic resonance, positron emission tomography, and single‐photon emission tomography have been evaluated to help clinical neurologists to provide a definite diagnosis.

123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography and 123I-metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study

To compare the diagnostic value of striatal 123I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (123I‐FP‐CIT) single photon emission computed tomography (SPECT) and 123I‐metaiodobenzylguanidine (123I‐MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types.

Recommendations from the Italian Interdisciplinary Working Group (AIMN, AIP, SINDEM) for the utilization of amyloid imaging in clinical practice

Positron emission tomography (PET) of brain amyloid is a technology that has been approved by Food and Drug Administration and European Medical Agency, but its clinical utility in medical practice requires careful definition. To provide guidance to italian dementia care practitioners, patients, and caregivers, a group of experts from “Associazione Italiana di Medicina Nucleare” (AIMN), “Associazione Italiana di Psicogeriatria” (AIP) and “Società Italiana per lo Studio delle Demenze” (SINDEM) convened the Italian Interdisciplinary Working Group on Amyloid Imaging. The Working Group considered a range of clinical scenarios in which amyloid PET should be recommended. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these recommendations. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific recommended use criteria were agreed to define the types of patients and clinical circumstances in which amyloid PET could be used. Both correct and incorrect uses were considered and formulated. Because both dementia care and amyloid-PET technology are in active development, these recommendations will require periodic reassessment.

Proposal for an optimized protocol for intravenous administration of insulin in diabetic patients undergoing 18f-fdg Pet/ct

The objective of this study was to evaluate the usefulness and impact of insulin administration before an 18F-FDG PET/computed tomography (CT) examination in diabetic patients in order to propose an optimized protocol that can reduce blood glucose levels without increasing muscular 18F-FDG uptake. A total of 130 patients underwent an 18F-FDG PET/CT. Twenty patients had glucose levels greater than 180 mg/dl and received endovenous insulin before 18F-FDG injection (group 1); 10 patients had glucose levels greater than 160 mg/dl and lower than 200 mg/dl and received no insulin (group 2); 100 patients were euglycemic (group 3). Biodistribution was adequate in 19 of 20 patients in group 1. Values of standardized uptake value in the gluteal muscle were 0.50±0.18 for group 1, 0.48±0.10 for group 2, and 0.49±0.08 for group 3; no significant differences in muscular 18F-FDG uptake could be found among the three groups. No adverse events were recorded. In conclusion, our protocol has been demonstrated to be safe and effective, with only a minor impact on glucose biodistribution and apparently without affecting PET accuracy.