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Item does not contain fulltext, Background: CSF and imaging biomarkers are needed for the etiological diagnosis of neurocognitive disorders, but evidence is incomplete on their rational use in the clinic. Since October 2020, a European task force has been defining an evidence-based diagnostic workflow, where incomplete evidence is filled by the opinion of experts. Herein, we report the preliminary results through January 2022. Method: A Delphi method was used to reach consensus. Eleven pertinent European scientific societies delegated two panelists each to join Delphi rounds and voting. Consensus was set at 70% of consistent responses. Result: In the 5 voting rounds completed so far, panelists defined clinical setting (specialist outpatient service) and stage of application (prodromal and mild dementia) of the workflow, patients’ age window of biomarkers use (strongly encouraged below 70 years and of limited usefulness over 85). Workflow is configurated to be patient-centered and structured on three levels of assessment (W): W1, definition of clinical profiles based on the combined results of MRI, neuropsychology, blood tests; W2, choice of first-line biomarkers according to the main clinical suspicion (i.e., FDG-PET for frontotemporal lobar degeneration and motor tauopathies, dopamine SPECT/PET for Lewy body spectrum disorders, and CSF biomarkers either for Alzheimer’s disease or in cases with inconclusive neuropsychological and/or MRI findings, whereas no biomarker was indicated in suspected vascular cognitive impairment); W3, selection of a second-line biomarker when results of first-line biomarkers are inconsistent with diagnostic hypothesis (i.e., not typical FDG-PET pattern) or uninformative (i.e., borderline CSF amyloid results) or not sufficient to rule out other etiologies (i.e., amyloid-positive and tau-negative CSF results) or when a diagnosis remains possible despite a negative first-line biomarker (e.g., normal dopamine SPECT/PET in suspected prodromal dementia with Lewy bodies). Conc

Background: Brain atrophy appears during the progression of multiple sclerosis (MS) and is associated with the disability caused by the disease. Methods: We investigated global and regional grey matter (GM) and white matter (WM) volumes, WM lesion load, and corpus callosum index (CCI), in benign relapsing-remitting MS (BRRMS, n = 35) with and without any treatment and compared those to aggressive relapsing-remitting MS (ARRMS, n = 46). Structures were analyzed by using an automated MRI quantification tool (cNeuro®). Results: The total brain and cerebral WM volumes were larger in BRRMS than in ARRMS (p = .014, p = .017 respectively). In BRRMS, total brain volumes, regional GM volumes, and CCI were found similar whether or not disease-modifying treatment (DMT) was used. The total (p = .033), as well as subcortical (p = .046) and deep WM (p = .041) lesion load volumes were larger in BRRMS patients without DMT. Cortical GM volumes did not differ between BRRMS and ARRMS, but the volumes of total brain tissue (p = .014) and thalami (p = .003) were larger in patients with BRRMS compared to ARRMS. A positive correlation was found between CCI and whole-brain volume in both BRRMS (r = .73, p < .001) and ARRMS (r = .80, p < .01). Conclusions: Thalamic volume is the most prominent measure to differentiate BRRMS and ARRMS. Validation of automated quantification of CCI provides an additional applicable MRI biomarker to detect brain atrophy in MS.

Extrapyramidal (EP) symptoms are a known feature in a subpopulation of patients with behavioral variant frontotemporal dementia (bvFTD). Concomitant EP symptoms with FTD-like neuropsychiatric symptoms are also core features in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). This complicates the early diagnosis of these disorders. Our retrospective register study aimed to discover imaging (MRI and FDG-PET) biomarkers to differentiate PSP, CBD, and bvFTD patients with extrapyramidal symptoms (EP +) from bvFTD patients without EP symptoms (EP-). The records of 2751 patients were screened for the diagnoses and presence of EP symptoms. A total of 222 patients were submitted to imaging analysis and applicable imaging data were recovered from 139 patients. Neuroimaging data were analyzed using Freesurfer software. In the whole cohort, EP + patients showed lower volumes of gray matter compared to EP- patients in the putamen (p = 0.002), bilateral globus pallidum (p = 0.002, p = 0.042), ventral diencephalon (p = 0.002) and brain stem (p < 0.001). In the bvFTD subgroup, there was volumetric difference between EP + and EP− patients in the brain stem. FDG-PET scans in the bvFTD patient subgroup showed that EP + patients had comparative hypometabolism of the superior cerebellar peduncle (SCP) and the frontal lobes. We discovered that EP symptoms are linked to brainstem atrophy in bvFTD patients and the whole cohort. Also, evident hypometabolism in the SCP of bvFTD EP + patients was detected as compared to bvFTD EP− patients. This could indicate that the EP symptoms in these diseases have a more caudal origin in the brainstem than in Parkinson’s disease.

Objectives: Our goal was to evaluate whether four-dimensional (4D) flow magnetic resonance imaging (MRI) can predict the growth rate of dilatation of the ascending aorta (AA) in patients with a tricuspid, normally functioning aortic valve. Methods: In this prospective clinical study, aortic 4D flow MRI was performed at the Kuopio University Hospital on 30 patients diagnosed with AA dilatation (maximum diameter >40 mm) between August 2017 and July 2020. The MRI was repeated after a 1-year follow-up, with AA dimensions and 4D flow parameters analysed retrospectively at both time points. The standard error of measurement was used to assess the statistical significance of the growth rate of AA dilatation. Flow displacement (FD) was transformed to a class-scaled parameter using FD ≥5% as a threshold. Results: Statistically significant growth [median 2.1 mm (1.5–2.2 mm); P = 0.03] was detected in 6 male patients (20%); the AA diameter remained unchanged [0.2 mm (−0.3 to 0.9 mm)] in 24 patients (80%). An increased FD at the baseline was associated with significant growth during the 1-year follow-up in the proximal AA. An association was detected between decreased total wall shear stress and significant aortic growth in the inner curve of the sinotubular junction [529 mPa (449–664 mPa) vs 775 mPa (609–944 mPa); P = 0.03] and the anterior side of the proximal aortic arch [356 mPa (305–367 mPa) vs 493 mPa (390–586 mPa); P < 0.001]. Conclusions: FD and decreased wall shear stress seem to be associated with significant growth of AA dilatation at the 1-year follow-up. Thus, 4D flow MRI might be useful in assessing risk for AA diameter growth in patients with a tricuspid aortic valve.

Background: The heart’s position determined as the heart–aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. Purpose: To investigate whether VAT and aortic length influence the HAA. Material and methods: We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. Results: A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°–130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°–124.7°) in patients with excessive VAT (P < 0.001). Conclusion: An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients.

Objectives: The aim of this study was to evaluate whether the orientation of the heart, measured as an angle between the long axis of the heart and ascending aorta midline (heart-aorta-angle, HAA), associates with ascending aortic (AA) dilatation. Furthermore, the association between HAA and wall shear stress (WSS) was studied. Methods: HAA was retrospectively measured in 1000 consecutive coronary artery computed tomographic angiography (CCTA) images in patients with low-to-moderate pretest probability for coronary artery disease (CAD). To evaluate the effects of HAA on AA flow, 4D flow MRI was performed for 28 patients with AA dilatation (> 40 mm) and WSS was analyzed. Results: The mean age of patients undergoing CCTA was 52.9 ± 9.8 years; 66.5% were women. Their median HAA was 128.7° and interquartile range 123.3–134.1°. HAA was significantly smaller in patients with dilated AA (median 126.7° [121.3–130.8°]) compared with the patients with normal AA (median 129.5° [124.3–135.3°], p < 0.001). HAA was smaller in males (p < 0.001) and in patients with diabetes (p = 0.016), hypertension (p = 0.001), CAD (p = 0.003), hypercholesterolemia (p < 0.001), and bicuspid aortic valve (p = 0.025) than without these factors. In a subpopulation without any of these underlying diseases (n = 233), HAA was still significantly smaller in the patients with dilated AA (median 127.9° [124.3–134.3°]) compared with patients with normal AA (median 131.9° [127.6–136.9°], p = 0.013). In 4D flow MRI, a smaller HAA correlated with increased total WSS in the outer curvature of the proximal AA (r = − 0.510, p = 0.006). Conclusions: A smaller HAA associates with AA dilatation and affects the blood flow in the proximal AA.

Our aim was to investigate the association between behavioral symptoms of agitation, disinhibition, irritability, elation, and aberrant motor behavior to frontal brain volumes in a cohort with various neurodegenerative diseases. A total of 121 patients with mild cognitive impairment (MCI, n = 58), Alzheimer's disease (AD, n = 45) and behavioral variant frontotemporal dementia (bvFTD, n = 18) were evaluated with a Neuropsychiatric Inventory (NPI). A T1-weighted MRI scan was acquired for each participant and quantified with a multi-atlas segmentation method. The volumetric MRI measures of the frontal lobes were associated with neuropsychiatric symptom scores with a linear model. In the regression model, we included CDR score and TMT B time as covariates to account for cognitive and executive functions. The brain volumes were corrected for age, gender and head size. The total behavioral symptom score of the five symptoms of interest was negatively associated with the volume of the subcallosal area (β = −0.32, p = 0.002). High disinhibition scores were associated with reduced volume in the gyrus rectus (β = −0.30, p = 0.002), medial frontal cortex (β = −0.30, p = 0.002), superior frontal gyrus (β = −0.28, p = 0.003), inferior frontal gyrus (β = −0.28, p = 0.005) and subcallosal area (β = −0.28, p = 0.005). Elation scores were associated with reduced volumes of the medial orbital gyrus (β = −0.30, p = 0.002) and inferior frontal gyrus (β = −0.28, p = 0.004). Aberrant motor behavior was associated with atrophy of frontal pole (β = −0.29, p = 0.005) and the subcallosal area (β = −0.39, p < 0.001). No significant associations with frontal brain volumes were found for agitation and irritability. We conclude that the subcallosal area may be common neuroanatomical area for behavioral symptoms in neurodegenerative diseases, and it appears to be independent of disease etiology.

Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (general health advice). This study reports exploratory analyses of brain MRI measures. Methods: FINGER targeted 1260 older individuals from the general Finnish population. Participants were 60–77 years old, at increased risk for dementia but without dementia/substantial cognitive impairment. Brain MRI scans were available for 132 participants (68 intervention, 64 control) at baseline and 112 participants (59 intervention, 53 control) at 2 years. MRI measures included regional brain volumes, cortical thickness, and white matter lesion (WML) volume. Cognition was assessed at baseline and 1- and 2-year visits using a comprehensive neuropsychological test battery. We investigated the (1) differences between the intervention and control groups in change in MRI outcomes (FreeSurfer 5.3) and (2) post hoc sub-group analyses of intervention effects on cognition in participants with more versus less pronounced structural brain changes at baseline (mixed-effects regression models, Stata 12). Results: No significant differences between the intervention and control groups were found on the changes in MRI measures. Beneficial intervention effects on processing speed were more pronounced in individuals with higher baseline cortical thickness in Alzheimer’s disease signature areas (composite measure of entorhinal, inferior and middle temporal, and fusiform regions). The randomization group × time × cortical thickness interaction coefficient was 0.198 (p = 0.021). A similar trend was observed for higher hippocampal volume (group × time × hippocampus volume interaction coefficient 0.1149, p = 0.085). Conclusions: The FINGER MRI exploratory sub-study did not show s

Background: The relationship between blood flow characteristics and ascending aortic (AA) dilatation has not been studied in patients with a tricuspid aortic valve (TAV) without aortic stenosis. Purpose: To evaluate whether 4D flow characteristics determined in MRI are related to AA dilatation by comparing dilated AA and nondilated AA subjects with TAV. Study Type: Prospective. Population: Twenty patients with dilated AA and 20 age‐matched patients with nondilated AA. Field Strength/Sequence: 1.5T/4D flow, 2D flow, and anatomic images. Assessment: Altogether, 16 different 4D flow parameters were assessed in 10 planes in the thoracic aorta. Intra‐ and interobserver reproducibility were analyzed. Statistical Tests: Independent t‐test for normally distributed and the Mann–Whitney test for skewed distributed parameters were used. A paired‐samples t‐test was used to compare 2D and 4D flow parameters. Intraclass correlation coefficient (ICC) was used in intra‐ and interobserver reproducibility analysis. Results: Aortic flow was displaced from the centerline of the aorta in the proximal and tubular planes. Flow displacement (FD) was greatest in the proximal plane of AA and was higher in dilated AA (4.5%, range 3.0–5.8%) than in nondilated AA (2.0%, 1.0–3.0%, P < 0.001). Total wall shear stress (WSS) values were 1.3 ± 0.4 times higher on the displaced side than on the opposite side of the aorta (P < 0.01). The circumferential WSS (WSSC) ratio to total WSS was greater in dilated AA, being 0.48 ± 0.11 vs. 0.32 ± 0.09 in the inner curvature of the proximal AA (P < 0.001) and 0.37 ± 0.11 vs. 0.26 ± 0.07 in the whole aortic ring in the distal AA (P < 0.001). Depending on 4D flow parameters, reproducibility varied from excellent (ICC = 0.923) to very low (ICC = 0.204). Data Conclusion: The present study demonstrates that 4D flow measurements help to visualize the pathological flow patterns related to aortic dilatation. Flow displacement and an increased WSSc