Prevalence of Amyloid Positron Emission Tomographic Positivity in Poststroke Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is common after stroke and associated with poor outcome. However, the mechanisms underlying poststroke MCI (PS-MCI) are insufficiently understood. We performed amyloid-ß positron emission tomography (PET) in a prospective cohort of stroke survivors to determine the role of amyloid pathology in PS-MCI. METHODS: We studied 178 consecutive patients enrolled into the prospective DEDEMAS study (Determinants of Dementia After Stroke). Follow-up visits 6 months post stroke included detailed cognitive testing, standardized magnetic resonance imaging, and amyloid-ß imaging using flutemetamol ((18)F) PET. MCI was defined by the modified Petersen criteria. Amyloid-positivity was assessed visually and quantitatively. Fifty-six (31%) patients agreed to undergo PET imaging. RESULTS: Thirty-eight (68%) patients who consented to PET imaging had PS-MCI. Visual assessment revealed amyloid PET positivity in 2 (5%) of the 38 PS-MCI patients and in 2 (11%) of the 18 cognitively healthy stroke survivors. There was no correlation between flutemetamol ((18)F) standardized uptake value ratios and cognitive scores in the 56 patients. PS-MCI patients had significant cognitive impairments on executive function (P<0.01) and memory tests (P<0.01) when compared with cognitively healthy stroke survivors (P<0.01). CONCLUSIONS: The prevalence of amyloid-pathology in patients with PS-MCI is not increased when compared with cognitively healthy stroke survivors and to recent estimates for cognitively healthy elderly subjects. Factors other than amyloid-pathology likely contribute to the development of PS-MCI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01334749.

Impact of MRI-based Segmentation Artifacts on Amyloid- and FDG-PET Quantitation.

INTRODUCTION: Magnet resonance image (MRI)-based segmentations are widely used for clinical brain research, especially in conjunction with positron-emission-tomography (PET). Although artifacts due to segmentation errors arise commonly, the impact of these artifacts on PET quantitation has not yet been investigated systematically. Therefore, the aim of this study was to assess the effect of segmentation errors on [(18)F]-AV45 and [(18)F]-FDG PET quantitation, with and without correction for partial volume effects (PVE). MATERIAL AND METHODS: 119 subjects with both [(18)F]-AV45, and [(18)F]-FDG PET as well as T1-weighted MRI at baseline and at two-year follow-up were selected from the ADNI cohort, and their MRI brain images were segmented using PMOD 3.5. MRIs with segmentation artifacts were masked with the corresponding [(18)F]-FDG PET standard-uptake-value (SUV) images to elucidate and quantify the impact of artifacts on PET analyses for six defined volumes-of-interest (VOI). Artifact volumes were calculated for each VOI, together with error-[%] and root-mean-square-errors (RMSE) in uncorrected and PVE corrected SUV results for the two PET tracers. We also assessed the bias in longitudinal PET data. RESULTS: Artifacts occurred most frequently in the parietal cortex VOI. For [(18)F]-AV45 and [(18)F]-FDG PET, the percentage-errors were dependent on artifact volumes. PVEC SUVs were consequently more distorted than were their uncorrected counterparts. In static and longitudinal assessment, a small subgroup of subjects with large artifacts (≥1500 voxels; ≙5.06 cm³) accounted for much of the PET quantitation bias. CONCLUSION: Large segmentation artifacts need to be detected and resolved as they considerably bias PET quantitation, especially when PVEC is applied to PET data.

Hypometabolism in Brain of Cognitively Normal Patients with Depressive Symptoms is Accompanied by Atrophy-Related Partial Volume Effects.

Late life depression (LLD) even in subsyndromal stages shows high conversion rates from cognitively normal (CN) to mild cognitive impairment (MCI). Results of [(18)F]-fluorodesoxyglucose positron-emission-tomography (FDG-PET) were inconsistent in LLD patients, whereas atrophy was repeatedly described. Therefore, we set out to investigate FDG metabolism and the effect of atrophy correction (PVEC) in geriatric CN patients with depressive symptoms. 21 CN subjects with positive item for the depression category (DEP) in the Neuropsychiatric-Inventory-Questionnaire and 29 CN subjects with an absent depression item (NON-DEP) were selected from the ADNI cohort. FDG-PETs were analyzed in individual PET space using volumes-of-interest (VOI) and statistical-parametric-mapping (SPM) approaches. VOI- and MRI-based PVEC were applied to PET data. DEP subjects showed significant hypometabolism in fronto-temporal cortices and the posterior cingulate cortex (PCC) when contrasted against NON-DEP in uncorrected data. Both in VOI- and SPM-based approaches PVEC eliminated significance in PCC, while fronto-temporal regions remained significant or even attained significance such as in case of the left amygdala. Subsyndromally depressed CN subjects had decreased FDG metabolism in mood-related brain regions, which may be relevant to their elevated risk for conversion from CN to MCI. Methodological advances in PET analyses should be considered in future studies as PVEC relevantly changed results of FDG-PET for detecting apparent metabolic differences between DEP and NON-DEP subjects. Furthermore, VOI-based analyses in individual PET space will allow a more accurate consideration of variability in anatomy, especially in subcortical regions.