Publications by authors named "Frank Jessen"

293 Publications

Brain Health Services: organization, structure, and challenges for implementation. A user manual for Brain Health Services-part 1 of 6.

Alzheimers Res Ther 2021 Oct 11;13(1):168. Epub 2021 Oct 11.

Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.

Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy.An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population.We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services.
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http://dx.doi.org/10.1186/s13195-021-00827-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507194PMC
October 2021

Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6.

Alzheimers Res Ther 2021 Oct 11;13(1):169. Epub 2021 Oct 11.

College of Medicine and Health, University of Exeter, Exeter, UK.

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.
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http://dx.doi.org/10.1186/s13195-021-00895-4DOI Listing
October 2021

A microRNA signature that correlates with cognition and is a target against cognitive decline.

EMBO Mol Med 2021 Oct 11:e13659. Epub 2021 Oct 11.

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.

While some individuals age without pathological memory impairments, others develop age-associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study, we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3-microRNA signature that reflects key processes linked to neural homeostasis and inform about cognitive status. We furthermore provide evidence that expression changes in this signature represent multiple mechanisms deregulated in the aging and diseased brain and are a suitable target for RNA therapeutics.
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http://dx.doi.org/10.15252/emmm.202013659DOI Listing
October 2021

Cognitive profiles of patients with mild cognitive impairment due to Alzheimer's versus Parkinson's disease defined using a base rate approach: Implications for neuropsychological assessments.

Alzheimers Dement (Amst) 2021 14;13(1):e12223. Epub 2021 Sep 14.

Department of Neurodegenerative Diseases and Gerontopsychiatry University Hospital of Bonn University of Bonn Bonn Germany.

Introduction: Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD-MCI) compared to Parkinson's disease (PD-MCI) are rare.

Methods: Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery.

Results: Patients with AD-MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD-MCI showed lower standardized scores in a set-shifting measure as an executive task. A cross-validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD-MCI versus PD-MCI.

Discussion: The applied test battery successfully discriminated between AD-MCI and PD-MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.
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http://dx.doi.org/10.1002/dad2.12223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438680PMC
September 2021

A Cost-Consequence Analysis of Different Screening Procedures in Alzheimer's Disease: Results from the MOPEAD Project.

J Alzheimers Dis 2021 ;83(3):1149-1159

Fundació ACE (FACE), Barcelona, Spain.

Background: For care planning and support, under-detection and late diagnosis of Alzheimer's disease (AD) is a great challenge. Models of Patient-Engagement for Alzheimer's Disease (MOPEAD) is an EU-funded project aiming at testing different strategies to improve this situation.

Objective: To make a cost-consequence analysis of MOPEAD.

Methods: Four screening strategies were tested in five countries (Germany, the Netherlands, Slovenia, Spain, and Sweden): 1) a web-approach; 2) Open-House initiative; 3) in primary care; and 4) by diabetes specialists. Persons-at-risk of AD in all strategies were offered referral to a hospital-based specialist. The primary health-economic outcome was the cost per true-positive case (TP) of AD from the screened population.

Results: Of 2,847 screened persons, 1,121 screened positive (39%), 402 were evaluated at memory clinics (14%), and 236 got an AD diagnosis (8%). The cost per TP of those screened was €3,115 with the web-approach, €2,722 with the Open-House, €1,530 in primary care, and €1,190 by diabetes specialists. Sensitivity analyses that more likely reflect the real-world situation confirmed the results. The number-needed-to-screen was 30 with the web-approach, 8 with the Open-House and primary care, and 6 with the diabetes specialists.There were country differences in terms of screening rates, referrals to memory clinics, staff-types involved, and costs per TP.

Conclusion: In primary care and by the diabetes specialist, the costs per TP/screened population were lowest, but the capacity of such settings to identify cases with AD-risk must be discussed. Hence new diagnostic strategies such as web-solutions and Open-House initiatives may be valuable after modifications.
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http://dx.doi.org/10.3233/JAD-210303DOI Listing
January 2021

Social Cognition in Patients with Amnestic Mild Cognitive Impairment and Mild Dementia of the Alzheimer Type.

J Alzheimers Dis 2021 ;83(3):1173-1186

Department of Psychiatry, University Hospital Cologne, Medical Faculty, Cologne, Germany.

Background: Social cognition (SC) is a core criterion for neurocognitive disorders. However, findings in patients with amnestic mild cognitive impairment (aMCI) and dementia of the Alzheimer type (DAT) are inconsistent.

Objective: We report assessments of emotion recognition (ER), affective and cognitive theory of mind (ToM) in young (YC) and older controls (OC) compared to aMCI and DAT.

Methods: 28 aMCI, 30 DAT, 30 YC, and 29 OC received tests of SC and a comprehensive neuropsychological assessment. Analysis of covariance was used to determine group differences. Multiple regression models were applied to identify predictors for each SC task.

Results: In controls, OC performed worse in ER and both ToM tasks compared to YC except for one subtest. No significant differences were found between OC and patients concerning ER and affective ToM. In cognitive ToM, differences between OC and patients depended on content and cognitive load with significant impairment in DAT compared to OC. A cognitive composite score predicted SC in OC, but not in patients. Associations of SC with single cognitive domains were found in all groups with language and complex attention as best predictors. Not all variance of SC performance was explained by variance in cognitive domains.

Conclusion: Lower performance on SC tasks in OC versus YC was confirmed, although not all tasks were equally affected. With progressive cognitive impairment, cognitive ToM is more impaired than ER or affective ToM. SC seems to be at least partly independent of other cognitive domains, justifying its inclusion in batteries for dementia diagnostic.
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http://dx.doi.org/10.3233/JAD-201126DOI Listing
January 2021

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease: Results from the MOPEAD project.

Alzheimers Dement 2021 Jul 26. Epub 2021 Jul 26.

Eli Lilly and Company, Firenze, Italy.

Introduction: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis.

Methods: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care-based protocol for early detection of cognitive decline (PC), and (4) a tertiary care-based pre-screening at diabetologist clinics (DC).

Results: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC).

Conclusion: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD.
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http://dx.doi.org/10.1002/alz.12441DOI Listing
July 2021

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Nat Commun 2021 06 7;12(1):3417. Epub 2021 Jun 7.

Servei de Neurologia, Hospital Universitari i Politècnic La Fe, Valencia, Spain.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.
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http://dx.doi.org/10.1038/s41467-021-22491-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184987PMC
June 2021

Resting-State Network Alterations Differ between Alzheimer's Disease Atrophy Subtypes.

Cereb Cortex 2021 Oct;31(11):4901-4915

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen 37075, Germany.

Several Alzheimer's disease (AD) atrophy subtypes were identified, but their brain network properties are unclear. We analyzed data from two independent datasets, including 166 participants (103 AD/63 controls) from the DZNE-longitudinal cognitive impairment and dementia study and 151 participants (121 AD/30 controls) from the AD neuroimaging initiative cohorts, aiming to identify differences between AD atrophy subtypes in resting-state functional magnetic resonance imaging intra-network connectivity (INC) and global and nodal network properties. Using a data-driven clustering approach, we identified four AD atrophy subtypes with differences in functional connectivity, accompanied by clinical and biomarker alterations, including a medio-temporal-predominant (S-MT), a limbic-predominant (S-L), a diffuse (S-D), and a mild-atrophy (S-MA) subtype. S-MT and S-D showed INC reduction in the default mode, dorsal attention, visual and limbic network, and a pronounced reduction of "global efficiency" and decrease of the "clustering coefficient" in parietal and temporal lobes. Despite severe atrophy in limbic areas, the S-L exhibited only marginal global network but substantial nodal network failure. S-MA, in contrast, showed limited impairment in clinical and cognitive scores but pronounced global network failure. Our results contribute toward a better understanding of heterogeneity in AD with the detection of distinct differences in functional connectivity networks accompanied by CSF biomarker and cognitive differences in AD subtypes.
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http://dx.doi.org/10.1093/cercor/bhab130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491689PMC
October 2021

Binding characteristics of [F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET.

J Cereb Blood Flow Metab 2021 May 27:271678X211018904. Epub 2021 May 27.

Center for Neuropathology and Prion Research, University Hospital of Munich, LMU Munich, Munich, Germany.

The novel tau-PET tracer [F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer's disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2: 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p < 0.0001), lower DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), lower SUVR (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies.
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http://dx.doi.org/10.1177/0271678X211018904DOI Listing
May 2021

Feasibility of short imaging protocols for [F]PI-2620 tau-PET in progressive supranuclear palsy.

Eur J Nucl Med Mol Imaging 2021 11 22;48(12):3872-3885. Epub 2021 May 22.

Department of Psychiatry, University Hospital Cologne, Cologne, Germany.

Purpose: Dynamic 60-min positron emission tomography (PET) imaging with the novel tau radiotracer [F]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [F]PI-2620 tau-PET imaging of PSP.

Methods: Thirty-seven patients with PSP Richardson syndrome (PSP-RS) were evaluated together with ten HCs. [F]PI-2620 PET was performed by a dynamic 60-min scan. Distribution volume ratios (DVRs) were calculated using full and truncated scan durations (0-60, 0-50, 0-40, 0-30, and 0-20 min p.i.). Standardized uptake value ratios (SUVrs) were obtained 20-40, 30-50, and 40-60 min p.i.. All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP-RS from HCs in predefined subcortical and cortical target regions (effect size, area under the curve (AUC), multi-region classifier).

Results: 0-50 and 0-40 DVR showed equivalent effect sizes as 0-60 DVR (averaged Cohen's d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0-30 or 0-20 DVR. The 20-40 SUVr indicated the best performance of all static acquisition windows (averaged Cohen's d: 0.99). The globus pallidus internus discriminated patients with PSP-RS and HCs at a similarly high level for 0-60 DVR (AUC: 0.96), 0-40 DVR (AUC: 0.96), and 20-40 SUVr (AUC: 0.94). The multi-region classifier sensitivity of these time windows was consistently 86%.

Conclusion: Truncated and static imaging windows can be used for [F]PI-2620 PET imaging of PSP. 0-40 min dynamic scanning offers the best balance between accuracy and economic scanning.
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http://dx.doi.org/10.1007/s00259-021-05391-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484138PMC
November 2021

[Predictive Diagnosis of Alzheimer's Dementia].

Fortschr Neurol Psychiatr 2021 May 18;89(5):254-266. Epub 2021 May 18.

Expanding technologies of early disease detection allow to identify Alzheimer's disease (AD) long before symptom onset. Hence, patients are increasingly demanding for these diagnostic procedures. Biomarker-based early detection of AD is therefore increasingly important in the clinical work-up. This article gives an overview of predictive procedures in the field of Alzheimer's dementia.
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http://dx.doi.org/10.1055/a-1370-3142DOI Listing
May 2021

Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline.

Front Aging Neurosci 2021 21;13:626974. Epub 2021 Apr 21.

Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.

The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases. We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups. Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode. HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.
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http://dx.doi.org/10.3389/fnagi.2021.626974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097178PMC
April 2021

Mediterranean Diet, Alzheimer Disease Biomarkers and Brain Atrophy in Old Age.

Neurology 2021 May 5. Epub 2021 May 5.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.

Objective: To determine if following a Mediterranean-like diet (MeDi) relates to cognitive functions and biomarkers for Alzheimer's disease (AD), we analyzed cross-sectional data from the German Longitudinal Cognitive Impairment and Dementia Study METHOD: The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 AD relatives, 209 SCD and 81 MCI). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aβ42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis.

Results: Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (β±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aβ42/40 ratio, β±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (β±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aβ42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status.

Conclusion: Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications.
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http://dx.doi.org/10.1212/WNL.0000000000012067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253566PMC
May 2021

Effects of a Mindfulness-Based Intervention versus Health Self-Management on Subclinical Anxiety in Older Adults with Subjective Cognitive Decline: The SCD-Well Randomized Superiority Trial.

Psychother Psychosom 2021;90(5):341-350. Epub 2021 Apr 19.

Swiss Center for Affective Sciences, Department of Medicine and Department of Psychology, Department of Political Science and International Relations, University of Geneva, Geneva, Switzerland.

Introduction: Older adults experiencing subjective cognitive decline (SCD) have a heightened risk of developing dementia and frequently experience subclinical anxiety, which is itself associated with dementia risk.

Objective: To understand whether subclinical anxiety symptoms in SCD can be reduced through behavioral interventions.

Methods: SCD-Well is a randomized controlled trial designed to determine whether an 8-week mindfulness-based intervention (caring mindfulness-based approach for seniors; CMBAS) is superior to a structurally matched health self-management program (HSMP) in reducing subclinical anxiety. Participants were recruited from memory clinics at 4 European sites. The primary outcome was change in anxiety symptoms (trait subscale of the State-Trait Anxiety Inventory; trait-STAI) from pre- to postintervention. Secondary outcomes included a change in state anxiety and depression symptoms postintervention and 6 months postrandomization (follow-up).

Results: One hundred forty-seven participants (mean [SD] age: 72.7 [6.9] years; 64.6% women; CMBAS, n = 73; HSMP, n = 74) were included in the intention-to-treat analysis. There was no difference in trait-STAI between groups postintervention (adjusted change difference: -1.25 points; 95% CI -4.76 to 2.25) or at follow-up (adjusted change difference: -0.43 points; 95% CI -2.92 to 2.07). Trait-STAI decreased postintervention in both groups (CMBAS: -3.43 points; 95% CI -5.27 to -1.59; HSMP: -2.29 points; 95% CI -4.14 to -0.44) and reductions were maintained at follow-up. No between-group differences were observed for change in state anxiety or depression symptoms.

Conclusions: A time-limited mindfulness intervention is not superior to health self-management in reducing subclinical anxiety symptoms in SCD. The sustained reduction observed across both groups suggests that subclinical anxiety symptoms in SCD are modifiable. ClinicalTrials.gov identifier: NCT03005652.
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http://dx.doi.org/10.1159/000515669DOI Listing
April 2021

Identification of undiagnosed dementia cases using a web-based pre-screening tool: The MOPEAD project.

Alzheimers Dement 2021 08 15;17(8):1307-1316. Epub 2021 Apr 15.

Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.

Introduction: Innovative patient engagement models are required to identify people with prodromal and mild Alzheimer's disease who are "hidden" in their communities and not normally found in a memory clinic setting.

Methods: A marketing campaign and a web-based pre-screening tool were used to identify individuals at risk of dementia in five European countries. Harmonized clinical evaluation of these patients was performed in participating memory clinics within the MOPEAD project.

Results: A total of 1487 individuals completed the pre-screening, with 547 of them found to be at risk of dementia (36.8%). Among the subset of 91 patients with a positive pre-screening result that underwent full clinical evaluation, 49 (53.8%) were diagnosed with either mild cognitive impairment or Alzheimer's disease.

Conclusion: This novel web-based pre-screening tool showed to be a valid strategy to identify undiagnosed people with cognitive impairment.
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http://dx.doi.org/10.1002/alz.12297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453736PMC
August 2021

General practitioners' attitude toward early and pre-dementia diagnosis of AD in five European countries-A MOPEAD project survey.

Alzheimers Dement (Amst) 2021 23;13(1):e12130. Epub 2021 Feb 23.

Department of Psychiatry University of Cologne Faculty of Medicine and University Hospital Cologne Cologne Germany.

Introduction: General practitioners (GPs) play a key role in early identification of dementia, yet diagnosis is often missed or delayed in primary care. As part of the multinational Models of Patient Engagement for Alzheimer's Disease project, we assess GPs' attitude toward early and pre-dementia diagnosis of AD and explore barriers to early diagnosis.

Methods: Our survey covered general attitude toward early diagnosis, diagnostic procedures, resources, and opinion on present and future treatment options across five European countries.

Results: In total 343 GPs completed the survey; 74% of GPs indicated that an early diagnosis is valuable. There were country-specific differences in GPs' perceptions of reimbursement and time available for the patient. If a drug were available to slow down the progression of AD, 59% of the GPs would change their implementation of early diagnosis.

Discussion: Our findings provide insight into GPs' attitudes by exploring differences in perception and management of early diagnosis.
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http://dx.doi.org/10.1002/dad2.12130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901232PMC
February 2021

Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer's Dementia in the Oldest Old.

Nutrients 2021 Jan 30;13(2). Epub 2021 Jan 30.

German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany.

Background: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties.

Methods: We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer's disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD.

Results: During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia.

Conclusions: Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.
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http://dx.doi.org/10.3390/nu13020461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912244PMC
January 2021

Biomarker-Based Risk Prediction of Alzheimer's Disease Dementia in Mild Cognitive Impairment: Psychosocial, Ethical, and Legal Aspects.

J Alzheimers Dis 2021 ;80(2):601-617

Cologne Center for Ethics, Rights, Economics, and Social Sciences of Health (ceres), University of Cologne, Cologne, Germany.

Background: Today, a growing number of individuals with mild cognitive impairment (MCI) wish to assess their risk of developing Alzheimer's disease (AD) dementia. The expectations as well as the effects on quality of life (QoL) in MCI patients and their close others through biomarker-based dementia risk estimation are not well studied.

Objective: The PreDADQoL project aims at providing empirical data on effects of such prediction on QoL and at developing an ethical and legal framework of biomarker-based dementia risk estimation in MCI.

Methods: In the empirical study, 100 MCI-patients and their close others will be recruited from two sites (Germany and Spain). They receive standardized counselling on cerebrospinal fluid (CSF) biomarker-based prediction of AD dementia and a risk disclosure based on their AD biomarker status. A mixed methods approach will be applied to assess outcomes.

Results: The pilot-study yielded a specification of the research topics and newly developed questionnaires for the main assessment. Within this binational quantitative and qualitative study, data on attitudes and expectations toward AD risk prediction, QoL, risk communication, coping strategies, mental health, lifestyle changes, and healthcare resource utilization will be obtained. Together with the normative part of the project, an empirically informed ethical and legal framework for biomarker-based dementia risk estimation will be developed.

Conclusion: The empirical research of the PreDADQoL study together with the ethical and legal considerations and implications will help to improve the process of counselling and risk disclosure and thereby positively affect QoL and health of MCI-patients and their close others in the context of biomarker-based dementia risk estimation.
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http://dx.doi.org/10.3233/JAD-200484DOI Listing
September 2021

Multimodal MRI analysis of basal forebrain structure and function across the Alzheimer's disease spectrum.

Neuroimage Clin 2020 11;28:102495. Epub 2020 Nov 11.

German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117 Berlin, Germany.

Background: Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer's disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD. We further assessed effects of amyloid pathology on these changes.

Methods: Participants included healthy controls, and subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or AD dementia (ADD) from the multicenter DELCODE study. Resting-state functional MRI (rs-fMRI) and structural MRI data was available for 477 subjects, and a subset of 243 subjects also had DTI data available. Differences between diagnostic groups were investigated using seed-based FC, volumetric, and MD analyses of functionally defined anterior (a-cBF) and posterior (p-cBF) subdivisions of a cytoarchitectonic cBF region-of-interest. In complementary analyses groups were stratified according to amyloid status based on CSF Aβ42/40 biomarker data, which was available in a subset of participants.

Results: a-cBF and p-cBF subdivisions showed regional FC profiles that were highly consistent with previously reported patterns, but there were only minimal differences between diagnostic groups. Compared to controls, cBF volumes and MD were significantly different in MCI and ADD but not in SCD. The Aβ42/40 stratified analyses largely matched these results.

Conclusions: We reproduced subregion-specific FC profiles of the cBF in a clinical sample spanning the AD spectrum. At least in this multicentric cohort study, cBF-FC did not show marked changes along the AD spectrum, and multimodal MRI did not provide more sensitive measures of AD-related cBF changes compared to volumetry.
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http://dx.doi.org/10.1016/j.nicl.2020.102495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689403PMC
June 2021

Association between composite scores of domain-specific cognitive functions and regional patterns of atrophy and functional connectivity in the Alzheimer's disease spectrum.

Neuroimage Clin 2021 17;29:102533. Epub 2020 Dec 17.

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany.

Background: Cognitive decline has been found to be associated with gray matter atrophy and disruption of functional neural networks in Alzheimer's disease (AD) in structural and functional imaging (fMRI) studies. Most previous studies have used single test scores of cognitive performance among monocentric cohorts. However, cognitive domain composite scores could be more reliable than single test scores due to the reduction of measurement error. Adopting a multicentric resting state fMRI (rs-fMRI) and cognitive domain approach, we provide a comprehensive description of the structural and functional correlates of the key cognitive domains of AD.

Method: We analyzed MRI, rs-fMRI and cognitive domain score data of 490 participants from an interim baseline release of the multicenter DELCODE study cohort, including 54 people with AD, 86 with Mild Cognitive Impairment (MCI), 175 with Subjective Cognitive Decline (SCD), and 175 Healthy Controls (HC) in the AD-spectrum. Resulting cognitive domain composite scores (executive, visuo-spatial, memory, working memory and language) from the DELCODE neuropsychological battery (DELCODE-NP), were previously derived using confirmatory factor analysis. Statistical analyses examined the differences between diagnostic groups, and the association of composite scores with regional atrophy and network-specific functional connectivity among the patient subgroup of SCD, MCI and AD.

Result: Cognitive performance, atrophy patterns and functional connectivity significantly differed between diagnostic groups in the AD-spectrum. Regional gray matter atrophy was positively associated with visuospatial and other cognitive impairments among the patient subgroup in the AD-spectrum. Except for the visual network, patterns of network-specific resting-state functional connectivity were positively associated with distinct cognitive impairments among the patient subgroup in the AD-spectrum.

Conclusion: Consistent associations between cognitive domain scores and both regional atrophy and network-specific functional connectivity (except for the visual network), support the utility of a multicentric and cognitive domain approach towards explicating the relationship between imaging markers and cognition in the AD-spectrum.
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http://dx.doi.org/10.1016/j.nicl.2020.102533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770965PMC
June 2021

Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study.

Alzheimers Res Ther 2020 12 18;12(1):167. Epub 2020 Dec 18.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts.

Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence.

Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades.

Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.
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http://dx.doi.org/10.1186/s13195-020-00734-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749505PMC
December 2020

Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status.

J Alzheimers Dis 2021 ;79(2):493-509

German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald.

Background: Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework.

Objective: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus.

Methods: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB).

Results: ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAβ+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAβ+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAβ+) and precuneus SUVRFBB (both groups).

Conclusion: While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAβ+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum.
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http://dx.doi.org/10.3233/JAD-200472DOI Listing
September 2021

Detection and treatment of mental disorders in patients with coronary heart disease (MenDis-CHD): A cross-sectional study.

PLoS One 2020 14;15(12):e0243800. Epub 2020 Dec 14.

Department of Psychosomatics and Psychotherapy, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, North Rhine-Westphalia, Germany.

Mental disorders (MD) are associated with an increased risk of developing coronary heart disease (CHD) and with higher CHD-related morbidity and mortality. There is a strong recommendation to routinely screen CHD patients for MDs, diagnosis, and treatment by recent guidelines. The current study aimed at mapping CHD patients' (1) state of diagnostics and, if necessary, treatment of MDs, (2) trajectories and detection rate in healthcare, and (3) the influence of MDs and its management on quality of life and patient satisfaction. The design was a cross-sectional study in three settings (two hospitals, two rehabilitation clinics, three cardiology practices). CHD patients were screened for MDs with the Hospital Anxiety and Depression Scale (HADS), and, if screened-positive, examined for MDs with the Structured Clinical Interview for DSM-IV (SCID-I). Quality of Life (EQ-5D), Patient Assessment of Care for Chronic Conditions (PACIC), and previous routine diagnostics and treatment for MDs were examined. Descriptive statistics, Chi-squared tests, and ANOVA were used for analyses. Analyses of the data of 364 patients resulted in 33.8% positive HADS-screenings and 28.0% SCID-I diagnoses. The detection rate of correctly pre-diagnosed MDs was 49.0%. Physicians actively approached approximately thirty percent of patients on MDs; however, only 6.6% of patients underwent psychotherapy and 4.1% medication therapy through psychotherapists/psychiatrists. MD patients scored significantly lower on EQ-5D and the PACIC. The state of diagnostic and treatment of comorbid MDs in patients with CHD is insufficient. Patients showed a positive attitude towards addressing MDs and were satisfied with medical treatment, but less with MD-related advice. Physicians in secondary care need more training inadequately addressing mental comorbidity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243800PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735609PMC
February 2021

Comparison of Patient and Proxy Assessment of Patient-Centeredness in the Care of Coronary Heart Disease: A Cross Sectional Survey Using the PACIC-S11.1.

J Prim Care Community Health 2020 Jan-Dec;11:2150132720976235

University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Introduction: When making medical care more patient-centered, surveys on patients' and their relatives' experiences can be helpful in identifying opportunities for improvement. In cases where the targeted patients are unable to express their own perspective, for example, due to them being too young or suffering from severe impairments, proxies can serve as substitutes. Proxies are frequently used in care planning and consent. Nevertheless, it is unclear whether patients' assessments of how patient-centered their medical care is are similar to those of their proxies. This study aims to assess the level of consistency between patients' and their proxies' assessments using an adapted version of the Patient Assessment of Chronic Illness Care (PACIC) short form questionnaire.

Methods: In a cross-sectional study, patients with coronary heart disease were recruited at cardiologists' offices, rehabilitation clinics and hospitals. Participants were surveyed with regard to the perceived level of patient-centeredness during their care using an adapted version of the German PACIC short form (PACIC-S11.1). Correlations in the assessments made by each patient and their respective proxy were analyzed. On the level of the patients group and the relatives group differences between mean ratings for each item were compared using paired -tests.

Results: In total, 74 pairs of patients and proxies submitted the completed questionnaire. On the level of the individual patient/proxy pairs, no correlation, or significant but low correlation, was found between the ratings. On the group level, patients' and their proxies' item ratings were similar in the interpretation of averages, but still demonstrated statistically significant differences. Overall, patients rated their care as more patient-centered than their proxies did.

Conclusion: The study shows that, on the individual level, proxies' ratings do not necessarily reflect the patients' assessment of PCC. On the group level, the assessments of relatives regarding PCC are similar to those of the patients.

Trial Registration: German clinical trials register (Deutsches Register Klinischer Studien, DRKS) Registration Number: DRKS00012434 (URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012434).
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http://dx.doi.org/10.1177/2150132720976235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686633PMC
June 2021

Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy.

JAMA Neurol 2020 11;77(11):1408-1419

Center for Neuropathology and Prion Research, University Hospital of Munich, LMU Munich, Munich, Germany.

Importance: Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis.

Objective: To investigate the potential of the novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed PSP.

Design, Setting, And Participants: In this cross-sectional study, participants underwent dynamic 18F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019.

Main Outcomes And Measures: Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, 18F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex.

Results: Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP-non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable 18F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with 18F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP-non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region.

Conclusions And Relevance: This multicenter evaluation indicates a value of 18F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.
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http://dx.doi.org/10.1001/jamaneurol.2020.2526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341407PMC
November 2020

Prediction of dementia of Alzheimer type by different types of subjective cognitive decline.

Alzheimers Dement 2020 12 2;16(12):1745-1749. Epub 2020 Nov 2.

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Introduction: Subjective cognitive decline (SCD) is a risk condition for dementia, including dementia of Alzheimer type (DAT).

Methods: We report sensitivity, specificity, positive and negative predictive values (PPV, NPV) for conversion to all-cause dementia, and DAT in different SCD types (decline in memory, assocated worries, longitudinal consitency, of the AgeCoDe study (n = 2.402, 12 years follow-up).

Results: 82.7% of those converting to any dementia and 84.4% of those converting with DAT at follow-up, reported memory decline and fulfilled criteria of SCD at least at one time point before. SCD with worries at two consecutive time points showed a specificity of 92.2% for any dementia and also for DAT as well as a PPV of 44.3% for any dementia and of 36.9% for DAT at follow-up at the expense of low sensitivity.

Discussion: Different SCD subtypes were either sensitive or specific for future all-cause dementia and DAT in cognitively unimpaired individuals. Modest PPV of the most specific SCD subtypes were achieved in this low prevalence population.
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http://dx.doi.org/10.1002/alz.12163DOI Listing
December 2020

Neuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers-results from the DELCODE study.

Alzheimers Res Ther 2020 10 16;12(1):131. Epub 2020 Oct 16.

German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Early identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer's disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries.

Methods: We analyzed data of n = 687 participants from the German DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study, including the diagnostic groups SCD (n = 242), mild cognitive impairment (MCI, n = 115), AD (n = 77), CO (n = 209), and first-degree relatives of AD patients (REL, n = 44). The Neuropsychiatric Inventory Questionnaire (NPI-Q), Geriatric Depression Scale (GDS-15), and Geriatric Anxiety Inventory (GAI-SF) were used to assess NPS. We examined differences of NPS frequency between diagnostic groups. Logistic regression analyses were carried out to further investigate the relationship between NPS and cerebrospinal fluid (CSF) AD biomarkers, focusing on a subsample of cognitively unimpaired participants (SCD, REL, and CO), who were further differentiated based on reported worries.

Results: The numbers of reported NPS, depression scores, and anxiety scores were significantly higher in subjects with SCD compared to CO. The quantity of reported NPS in subjects with SCD was lower compared to the MCI and AD group. In cognitively unimpaired subjects with worries, low Aß42 was associated with higher rates of reporting two or more NPS (OR 0.998, 95% CI 0.996-1.000, p < .05).

Conclusion: These findings give insight into the prevalence of NPS in different diagnostic groups, including SCD and healthy controls. NPS based on informant report seem to be associated with underlying AD pathology in cognitively unimpaired participants who worry about cognitive decline.

Trial Registration: German Clinical Trials Register DRKS00007966 . Registered 4 May 2015.
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http://dx.doi.org/10.1186/s13195-020-00701-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566134PMC
October 2020

Evaluation of evidence grades in psychiatry and psychotherapy guidelines.

BMC Psychiatry 2020 10 12;20(1):503. Epub 2020 Oct 12.

Department of Psychiatry and Psychotherapy, University Hospital Munich, Ludwig-Maximilians Universität München, Nußbaumstraße 7, 80336, München, Germany.

Background: Information regarding the distribution of evidence grades in psychiatry and psychotherapy guidelines is lacking. Based on the German evidence- and consensus- based (S3) psychiatry and psychotherapy and the Scottish Intercollegiate Guidelines Network (SIGN) treatment guidelines, we aimed to specify how guideline recommendations are composed and to what extent recommendations are evidence-based.

Methods: Data was collected from all published evidence- and consensus-based S3-classified psychiatry and psychotherapy guidelines. As control conditions, data from German neurology S3-classified guidelines as well as data from recent SIGN guidelines of mental health were extracted. Two investigators reviewed the selected guidelines independently, extracted and analysed the numbers and levels of recommendations.

Results: On average, 45.1% of all recommendations are not based on strong scientific evidence in German guidelines of psychiatry and psychotherapy. A related pattern can be confirmed for SIGN guidelines, where the mean average of recommendations with lacking evidence is 33.9%. By contrast, in the German guidelines of neurology the average of such recommendations is 16.5%. A total of 24.5% of all recommendations in the guidelines of psychiatry and psychotherapy are classified as level A recommendations, compared to 31.6% in the field of neurology and 31.1% in the SIGN guidelines. Related patterns were observed for B and 0 level recommendations.

Conclusion: Guidelines should be practical tools to simplify the decision-making process based on scientific evidence. Up to 45% of all recommendations in the investigated guidelines of psychiatry and psychotherapy are not based on strong scientific evidence. The reasons for this high number remain unclear. Possibly, only a limited number of studies answer clinically relevant questions. Our findings thereby question whether guidelines should include non-evidence-based recommendations to be methodologically stringent and whether specific processes to develop expert-opinion statements must be implemented.
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http://dx.doi.org/10.1186/s12888-020-02897-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552557PMC
October 2020
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