Comparing two artificial intelligence software packages for normative brain volumetry in memory clinic imaging

Purpose To compare two artificial intelligence software packages performing normative brain volumetry and explore whether they could differently impact dementia diagnostics in a clinical context. Methods Sixty patients (20 Alzheimer’s disease, 20 frontotemporal dementia, 20 mild cognitive impairment) and 20 controls were included retrospectively. One MRI per subject was processed by software packages from two proprietary manufacturers, producing two quantitative reports per subject. Two neuroradiologists assigned forced-choice diagnoses using only the normative volumetry data in these reports. They classified the volumetric profile as “normal,” or “abnormal”, and if “abnormal,” they specified the most likely dementia subtype. Differences between the packages’ clinical impact were assessed by comparing (1) agreement between diagnoses based on software output; (2) diagnostic accuracy, sensitivity, and specificity; and (3) diagnostic confidence. Quantitative outputs were also compared to provide context to any diagnostic differences. Results Diagnostic agreement between packages was moderate, for distinguishing normal and abnormal volumetry (K = .41–.43) and for specific diagnoses (K = .36–.38). However, each package yielded high inter-observer agreement when distinguishing normal and abnormal profiles (K = .73–.82). Accuracy, sensitivity, and specificity were not different between packages. Diagnostic confidence was different between packages for one rater. Whole brain intracranial volume output differed between software packages (10.73%, p < .001), and normative regional data interpreted for diagnosis correlated weakly to moderately (rs = .12–.80). Conclusion Different artificial intelligence software packages for quantitative normative assessment of brain MRI can produce distinct effects at the level of clinical interpretation. Clinics should not assume that different packages are interchangeable, thus recommending internal evaluation of packages before adoption.

Comparing a Single Clinician Versus a Multidisciplinary Consensus Conference Approach for Dementia Diagnostics

Background: Evidence-based recommendations on the optimal evaluation approach for dementia diagnostics are limited. This impedes a harmonized workup across clinics and nations. Objective: To evaluate the diagnostic performance of a multidisciplinary consensus conference compared to a single clinician approach. Methods: In this prospective study, we enrolled 457 patients with suspected cognitive decline, from two European memory clinics. A diagnostic evaluation was performed at baseline independently in two ways: 1) by a single clinician and 2) at a multidisciplinary consensus conference. A syndrome diagnosis and an etiological diagnosis was made. The confidence in the diagnosis was recorded using a visual analogue scale. An expert panel re-evaluation diagnosis served as reference for the baseline syndrome diagnosis and a 12-24-month follow-up diagnosis for the etiological diagnosis. Results: 439 patients completed the study. We observed 12.5%discrepancy (k = 0.81) comparing the baseline syndrome diagnoses of the single clinician to the consensus conference, and 22.3%discrepancy (k = 0.68) for the baseline etiological diagnosis. The accuracy of the baseline etiological diagnosis was significantly higher at the consensus conference and was driven mainly by increased accuracy in the MCI group. Confidence in the etiological diagnosis at baseline was significantly higher at the consensus conference (p < 0.005), especially for the frontotemporal dementia diagnosis. Conclusion: The multidisciplinary consensus conference performed better on diagnostic accuracy of disease etiology and increased clinicians’ confidence. This highlights the importance of a multidisciplinary diagnostic evaluation approach for dementia diagnostics, especially when evaluating patients in the MCI stage.

Brain Structural Connectivity Differences in Patients with Normal Cognition and Cognitive Impairment

Advances in magnetic resonance imaging, particularly diffusion imaging, have allowed researchers to analyze brain connectivity. Identification of structural connectivity differences between patients with normal cognition, cognitive impairment, and dementia could lead to new biomarker discoveries that could improve dementia diagnostics. In our study, we analyzed 22 patients (11 control group patients, 11 dementia group patients) that underwent 3T MRI diffusion tensor imaging (DTI) scans and the Montreal Cognitive Assessment (MoCA) test. We reconstructed DTI images and used the Desikan–Killiany–Tourville cortical parcellation atlas. The connectivity matrix was calculated, and graph theoretical analysis was conducted using DSI Studio. We found statistically significant differences between groups in the graph density, network characteristic path length, small-worldness, global efficiency, and rich club organization. We did not find statistically significant differences between groups in the average clustering coefficient and the assortativity coefficient. These statistically significant graph theory measures could potentially be used as quantitative biomarkers in cognitive impairment and dementia diagnostics.

Cerebrospinal fluid α synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms

Extrapyramidal symptoms (EP) are not uncommon in Alzheimer’s Disease (AD); when present, they negatively influence the course of the disorder. A large proportion of AD patients shows concomitant Lewy bodies’ pathology post mortem. Total α Synuclein (αSyn) concentrations are frequently increased in the cerebrospinal fluid (CSF) of AD patients, but are decreased in Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn CSF concentrations in AD patients with EP (EP+) have not been reported so far. αSyn and the four Neurochemical Dementia Diagnostics (NDD) CSF biomarkers, (Aβ1-42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm, were measured in patients with positive NDD results and presence of extrapyramidal symptoms (NDD + / EP+; n = 26), in patients with positive NDD results and absence of extrapyramidal symptoms (NDD+ / EP−; n = 54), and in subjects with negative NDD results (NDD−; n = 34). Compared to the NDD− controls (379.8 ± 125.2 pg/mL), NDD+ patients showed, on average, highly significantly increased CSF αSyn (519 ± 141.3 pg/mL, p < 0.01), but without differences between NDD+ / EP+ and NDD+ / EP− subgroups (p = 0. 38). Moderate but highly significant association was observed between concentrations of αSyn and Tau (r = 0.47, p < 0.01) and pTau181 (r = 0.65, p < 0.01). Adjusted for diagnoses, age, and sex, subjects with more advanced neurodegeneration on neuroimaging showed significantly lower αSyn concentrations (p < 0.02). In the setting AD versus controls, the area under the receiver operating characteristic (ROC) curve was 0.804 [0.712; 0.896] with the sensitivity and the specificity of 0.863 and 0.618, respectively. αSyn in AD patients does not differentiate between subjects with- and without EP. Its increased average concentration reflects probably neurodegenerative process, and is not specific for any pathophysiologic mechanisms. Further studies are necessary to explain the role of CSF αSyn as a potential biomarker.

Factors influencing general practitioners’ perception of and attitude towards dementia diagnostics and care—results of a survey among primary care physicians in Germany

SummaryStudies have shown that primary care is not always effective when it comes to caring for people with dementia. In addition, general practitioners do not always use diagnostic instruments consistently. The aim of the study was to identify relevant factors that influence general practitioners’ attitudes and willingness with respect to consistent diagnosis and care. For this purpose, resources, viewpoints, and behavioral patterns of general practitioners with regard to dementia diagnostics as well as common challenges in everyday practice were recorded. In the course of a survey, a total of 2266 general practitioners in Hesse and Baden-Württemberg were interviewed between January and March 2020. In addition to the descriptive analysis, a t-test was used to determine significant differences between two groups. A univariate linear regression analysis was carried out to identify possible influencing factors. 81% of the respondents do provide dementia diagnostics; 51% are involved in the treatment. Most of them see the diagnostic work-up (77%), communication and compliance problems (73%), as well as the therapeutic support (71%) as common challenges. In addition, there are interface problems regarding the interdisciplinary cooperation. Some of the respondents express doubts about the value of early detection (41%). The general practitioners’ attitude with respect to dementia diagnostics and care is determined by influencing factors that relate to geriatric competencies, expectations of self-efficacy, the integration of practice staff, as well as the knowledge of and cooperation with counseling and care services. It seems advisable to strengthen the geriatric competence of general practitioners. Moreover, it appears essential to educate general practitioners more about support structures in the field of dementia care and to integrate them accordingly. In addition, practice staff should be more systematically involved in the identification and care of dementia patients.

Dementia diagnostics in general practitioner care

SummaryGeneral practitioner (GP) treatment of dementia is often criticized as being ineffective and not implemented consistently enough. The causes and specific standpoints of GPs have not previously been thoroughly investigated. This paper focuses on the reasons and the criticisms levelled at GPs with regard to diagnosing dementia, and identifies approaches to enable optimization. The analysis is based on 41 semi-structured interviews with GPs in Hesse, Germany, in 2018. During the course of a content analysis, the interviewees’ attitudes and behavioral patterns towards dementia diagnostics were to be analyzed. The results of the study show various challenges and problems of primary care in this field. The majority of the sample showed skepticism and reluctance with regard to the diagnosis of dementia. Six key problem areas were extracted from the interviews, which can be seen as root causes for the distance kept by GPs: 1) early delegation of patients due to role understanding, 2) attitude of pessimism towards dementia, 3) differential diagnosis perceived as an obstacle, 4) insufficient remuneration, 5) fear of patient stigmatization, and 6) lack of application. Some GPs demonstrated personal initiative with the aim of optimizing dementia diagnostics. Three approaches can be derived which could be used to improve the GP-based care of dementia: 1) self-efficacy, 2) differential diagnostics and treatment pathways, and 3) physician–patient communication.

Higher Level of Mismatch in APOEε4 Carriers for Amyloid-Beta Peptide Alzheimer’s Disease Biomarkers in Cerebrospinal Fluid

Cerebrospinal fluid (CSF) biomarkers are widely used in the diagnosis of dementia. Even though there is a causal correlation between apolipoprotein E ( APOE) genotype and amyloid-beta (Aβ), the determination of APOE is currently not supported by national or international guidelines. We compared parallel measured CSF biomarkers of two independent laboratories from 126 patients who underwent clinical dementia diagnostics regarding the APOE genotype. APOE ε4 reduces Aβ1-42 (Aβ42) and Aβ42 to Aβ 1-40 ratio (Aβ42/40) but not total Tau or phospho-181 Tau CSF levels. Higher discordance rates were observed for Aβ42 and subsequently for Aβ42/40 in APOE ε4 carriers compared with noncarriers, and the correlation between the two laboratories was significantly lower for Aβ42 in APOE ε4 positive patients compared with patients without APOE ε4. These observations demonstrate that the evaluation of CSF Aβ biomarkers needs to be interpreted carefully in the clinical context. Different immunoassays, disparate cutoff values, and APOE should be respected.