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Background: Neuroinflammation is a hallmark of the Alzheimer's disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates., Method: 134 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden). Four visual rating scales were applied to magnetic resonance imaging or computed tomography scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (WML), and posterior atrophy. Participants provided saliva samples for assessment of diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Three cortisol measures were used: the cortisol awakening response, total daily output, and the ratio of awakening to bedtime levels. Nineteen CSF neuroinflammation markers were categorized into five composite scores: proinflammatory cytokines, other cytokines, angiogenesis markers, vascular injury markers, and glial activation markers. Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation scores in relation to visual rating scales., Result: Higher levels of angiogenesis markers were associated with more severe WML. Some evidence was found for interactions between dysregulated diurnal cortisol patterns and greater neuroinflammation-related biomarkers in relation to more severe GCA and WML. No associations were found between cortisol patterns and visual rating scales., Conclusion: This study suggests an interplay between diurnal cortisol patterns and neuroinflammation in relation to brain structure. While this cross-sectional study does not provide information on causality or temporality, these findings suggest that neuroinflammation may be involved in the relationship between HPA-axis functioning and AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Visual rating scales are increasingly utilized in clinical practice to assess atrophy in crucial brain regions among patients with cognitive disorders. However, their capacity to predict Alzheimer's disease (AD)-related pathology remains unexplored, particularly within a heterogeneous memory clinic population. This study aims to assess the accuracy of a novel visual rating assessment, the antero-posterior index (API) scale, in predicting amyloid-PET status. Furthermore, the study seeks to determine the optimal cohort-based cutoffs for the medial temporal atrophy (MTA) and parietal atrophy (PA) scales and to integrate the main visual rating scores into a predictive model., Methods: We conducted a retrospective analysis of brain MRI and high-resolution TC scans from 153 patients with cognitive disorders who had undergone amyloid-PET assessments due to suspected AD pathology in a real-world memory clinic setting., Results: The API scale (cutoff ≥1) exhibited the highest accuracy (AUC = 0.721) among the visual rating scales. The combination of the cohort-based MTA and PA threshold with the API yielded favorable accuracy (AUC = 0.787). Analyzing a cohort of MCI/Mild dementia patients below 75 years of age, the API scale and the predictive model improved their accuracy (AUC = 0.741 and 0.813, respectively), achieving excellent results in the early-onset population (AUC = 0.857 and 0.949, respectively)., Conclusion: Our study emphasizes the significance of visual rating scales in predicting amyloid-PET positivity within a real-world memory clinic. Implementing the novel API scale, alongside our cohort-based MTA and PA thresholds, has the potential to substantially enhance diagnostic accuracy., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: Neurodegeneration in suspected Alzheimer's disease can be determined using visual rating or quantitative volumetric assessments. We examined the feasibility of volumetric measurements of gray matter (GMV) and hippocampal volume (HCV) and compared their diagnostic performance with visual rating scales in academic and non-academic memory clinics., Materials and Methods: We included 231 patients attending local memory clinics (LMC) in the Netherlands and 501 of the academic Amsterdam Dementia Cohort (ADC). MRI scans were acquired using local protocols, including a T1-weighted sequence. Quantification of GMV and HCV was performed using FSL and FreeSurfer. Medial temporal atrophy and global atrophy were assessed with visual rating scales. ROC curves were derived to determine which measure discriminated best between cognitively normal (CN), mild cognitive impairment (MCI), and Alzheimer's dementia (AD)., Results: Patients attending LMC (age 70.9 ± 8.9 years; 47% females; 19% CN; 34% MCI; 47% AD) were older, had more cerebrovascular pathology, and had lower GMV and HCV compared to those of the ADC (age 64.9 ± 8.2 years; 42% females; 35% CN, 43% MCI, 22% AD). While visual ratings were feasible in > 95% of scans in both cohorts, quantification was achieved in 94-98% of ADC, but only 68-85% of LMC scans, depending on the software. Visual ratings and volumetric outcomes performed similarly in discriminating CN vs AD in both cohorts., Conclusion: In clinical settings, quantification of GM and hippocampal atrophy currently fails in up to one-third of scans, probably due to lack of standardized acquisition protocols. Diagnostic accuracy is similar for volumetric measures and visual rating scales, making the latter suited for clinical practice. In a real-life clinical setting, volumetric assessment of MRI scans in dementia patients may require acquisition protocol optimization and does not outperform visual rating scales., Key Points: • In a real-life clinical setting, the diagnostic performance of visual rating scales is similar to that of automatic volumetric quantification and may be sufficient to distinguish Alzheimer's disease groups. • Volumetric assessment of gray matter and hippocampal volumes from MRI scans of patients attending non-academic memory clinics fails in up to 32% of cases. • Clinical MR acquisition protocols should be optimized to improve the output of quantitative software for segmentation of Alzheimer's disease-specific outcomes., (© 2022. The Author(s).)

Age-related brain atrophy is a common finding, but neurodegenerative diseases such as Alzheimer's disease are associated with accelerated atrophy of the medial temporal lobe. In current practice for brain atrophy evaluation, several rating scales are being used such as the medial temporal atrophy (MTA), global cortical atrophy-frontal subscale (GCA-F) and posterior atrophy (PA) scales. Practical cut-offs to differentiate between normal and advanced brain atrophy are needed, because of their possible usefulness as a biomarker. A retrospective study was performed over a 1-year period resulting in a total of 79 subjects [27 patients with Alzheimer's disease (AD), 27 patients with minimal cognitive impairment (MCI) and 25 control subjects]. The MTA, GCA-F and PA scales were applied blinded and independent by two raters. Possible age- and disease-related cut-offs were computed. The MTA scale showed significantly better diagnostic performances and inter-rater agreement than the PA and GCA-F scales. We could not confirm the suggested MTA cut-off for each decade. However, an MTA score of >1 and >1.75 was considered pathological, respectively, in the population under and over 70 years. MTA can be of use in making distinction between age-related atrophy and abnormal increase of atrophy. Systematic assessment of regional brain atrophy through the use of MTA in MRI images could be a useful biomarker in aiding the early diagnosis of Alzheimer's disease.

Background: Atrophy in the medial temporal lobe, frontal lobe and posterior cortex can be measured with visual rating scales such as the medial temporal atrophy (MTA), global cortical atrophy - frontal subscale (GCA-F) and posterior atrophy (PA) scales, respectively. However, practical cut-offs are urgently needed, especially now that different presentations of Alzheimer's disease (AD) are included in the revised diagnostic criteria., Aims: The aim of this study was to generate a list of practical cut-offs for the MTA, GCA-F and PA scales, for both diagnosis of AD and determining prognosis in mild cognitive impairment (MCI), and to evaluate the influence of key demographic and clinical factors on these cut-offs., Methods: AddNeuroMed and ADNI cohorts were combined giving a total of 1147 participants (322 patients with AD, 480 patients with MCI and 345 control subjects). The MTA, GCA-F and PA scales were applied and a broad range of cut-offs was evaluated., Results: The MTA scale showed better diagnostic and predictive performances than the GCA-F and PA scales. Age, apolipoprotein E (ApoE) ε4 status and age at disease onset influenced all three scales. For the age ranges 45-64, 65-74, 75-84 and 85-94 years, the following cut-offs should be used. MTA: ≥1.5, ≥1.5, ≥2 and ≥2.5; GCA-F, ≥1, ≥1, ≥1 and ≥1; and PA, ≥1, ≥1, ≥1 and ≥1, respectively, with an adjustment for early-onset ApoE ε4 noncarrier AD patients (MTA: ≥2, ≥2, ≥3 and ≥3; and GCA-F: ≥1, ≥1, ≥2 and ≥2, respectively)., Conclusions: If successfully validated in clinical settings, the list of practical cut-offs proposed here might be useful in clinical practice. Their use might also (i) promote research on atrophy subtypes, (ii) increase the understanding of different presentations of AD, (iii) improve diagnosis and prognosis and (iv) aid population selection and enrichment for clinical trials., (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

Background: In Alzheimer's disease (AD), some patients present with cognitive impairment other than episodic memory disturbances. We evaluated whether occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) could account for differences in cognitive domains affected., Methods: In 329 patients with AD, we assessed five cognitive domains: memory, language, visuospatial functioning, executive functioning, and attention. Magnetic resonance imaging (MRI) was rated visually for the presence of MTA and PA. Two-way analyses of variance were performed with MTA and PA as independent variables, and cognitive domains as dependent variables. Gender, age, and education were covariates. As PA is often encountered in younger patients, analyses were repeated after stratification for age of onset (early onset, ≤65 years)., Results: The mean age of the participants was 67 years, 175 (53%) were female, and the mean Mini-Mental State Examination (score±standard deviation) was 20±5 points. Based on dichotomized magnetic resonance imaging ratings, 84 patients (26%) had MTA and PA, 98 (30%) had MTA, 57 (17%) had PA, and 90 (27%) had neither. MTA was associated with worse performance on memory, language, and attention (all, P<.05), and PA was associated with worse performance on visuospatial and executive functioning (both, P<.05). Stratification for age showed in patients with late-onset AD (n=173) associations between MTA and impairment on memory, language, visuospatial functioning, and attention (all, P<.05); in early-onset AD (n=156), patients with PA tended to perform worse on visuospatial functioning., Conclusions: Regional atrophy is related to impairment in specific cognitive domains in AD. The prevalence of PA in a large set of patients with AD and its association with cognitive functioning provides support for the usefulness of this visual rating scale in the diagnostic evaluation of AD., (Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)