Cortical Tau Aggregation Patterns associated with Apraxia in Alzheimer's Disease.

Objectives: Apraxia is a core feature of Alzheimer's disease, but the pathomechanism of this characteristic symptom is not well understood. Here, we systematically investigated apraxia profiles in a well-defined group of patients with Alzheimer's disease (AD; N=32) who additionally underwent PET imaging with the second-generation tau PET tracer [18F]PI-2620. We hypothesized that specific patterns of tau pathology might be related to apraxic deficits. Methods: Patients (N=32) with a biomarker-confirmed diagnosis of Alzheimer's disease were recruited in addition to a sample cognitively unimpaired controls (CU 1 ; N=41). Both groups underwent in-depth neuropsychological assessment of apraxia (Dementia Apraxia Screening Test; DATE and the Cologne Apraxia Screening; KAS). In addition, static PET imaging with [18F]PI-2620 was performed to assess tau pathology in the AD patients. To specifically investigate the association of apraxia with regional tau-pathology, we compared the PET-data from this group with an independent sample of amyloid-negative cognitively intact participants (CU 2; N=54) by generation of z-score-deviation maps as well as voxel- based multiple regression analyses. Results: We identified significant clusters of tau-aggregation in praxis-related regions (e.g., supramarginal gyrus, angular gyrus, temporal, parietal and occipital regions) that were associated with apraxia. These regions were similar between the two apraxia assessments. No correlations between tau-tracer uptake in primary motor cortical or subcortical brain regions and apraxia were observed. Conclusions: These results suggest that tau deposition in specific cortical brain regions may induce local neuronal dysfunction leading to a dose-dependent functional decline in praxis performance.

Perceived Physical Health and Cognitive Behavioral Therapy vs Supportive Psychotherapy Outcomes in Adults With Late-Life Depression: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Physical diseases co-occur with late-life depression (LLD). The influence of physical diseases and the subjective perception of physical health (PPH) on treatment outcome in LLD, however, is not well understood. Objective: To assess the association of physical diseases and PPH with the outcomes of 2 different types of psychotherapy in LLD. Design, Setting, and Participants: This post hoc secondary analysis of a multicenter, observer-blinded, controlled, parallel-group randomized clinical trial assessed participants 60 years or older with moderate to severe depression recruited at 7 psychiatric-psychotherapeutic outpatient trial sites in Germany from October 1, 2018, to November 11, 2020. Data analysis was performed from April 1 to October 31, 2023. Interventions: Patients received LLD-specific cognitive behavioral therapy (LLD-CBT) or supportive unspecific intervention (SUI). Main Outcomes and Measures: Depression severity, response, and remission were measured during treatment and at 6-month follow-up by the change in the 30-item Geriatric Depression Scale (GDS) score. Physical health and PPH were assessed by the number of physical diseases, Charlson Comorbidity Index (CCI), and the World Health Organization Quality of Life Brief Version physical health subscale. Results: A total of 251 patients were randomized to LLD-CBT (n = 126) or SUI (n = 125), of whom 229 (mean [SD] age, 70.2 [7.1] years; 151 [66%] female) were included in the intention-to-treat analysis. Patients with low and moderate PPH at baseline had significantly less reduction in the GDS score across both treatment groups than patients with high PPH (estimated marginal mean difference [EMMD], 2.67; 95% CI, 0.37-4.97; P = .02 for low PPH and EMMD, 1.82; 95% CI, 0.22-3.42; P = .03 for moderate vs high PPH). Higher PPH at baseline was associated with higher likelihood of response (odds ratio [OR], 1.04; 95% CI, 1.00-1.06; P = .009) and remission at the end of treatment (OR, 1.04; 95% CI, 1.02-1.08; P = .002) and response (OR, 1.05; 95% CI, 1.02-1.08; P < .001) and remission at follow-up (OR, 1.06; 95% CI, 1.03-1.10; P < .001) across both treatment groups. However, a significant interaction of PPH with treatment group was observed with low PPH at baseline being associated with significantly larger reduction in GDS scores in SUI compared with LLD-CBT at the end of treatment (EMMD, -6.48; 95% CI, -11.31 to -1.64; P = .009) and follow-up (EMMD, -6.49; 95% CI, -11.51 to -1.47; P = .01). In contrast, patients with high PPH at baseline had a significantly greater reduction in GDS scores in LLD-CBT compared with SUI at all time points (week 5: EMMD, -4.08; 95% CI, -6.49 to -1.67; P = .001; end-of-treatment: EMMD, -3.67; 95% CI, -6.72 to -0.61; P = .02; and follow-up: EMMD, -3.57; 95% CI, -6.63 to -0.51; P = .02). The number of physical diseases or CCI at baseline did not have an effect on the change in GDS score, response, or remission, neither across both groups nor within either group. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, subjective PPH was associated with treatment outcome, response, and remission in psychotherapy of LLD. Patients with LLD responded differently to LLD-CBT and SUI, depending on their baseline PPH score. Treatment approaches for patients with LLD should address PPH in personalized interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03735576; Deutsches Register Klinischer Studien Identifier: DRKS00013769.

Machine Learning-Based Perivascular Space Volumetry in Alzheimer Disease.

OBJECTIVES: Impaired perivascular clearance has been suggested as a contributing factor to the pathogenesis of Alzheimer disease (AD). However, it remains unresolved when the anatomy of the perivascular space (PVS) is altered during AD progression. Therefore, this study investigates the association between PVS volume and AD progression in cognitively unimpaired (CU) individuals, both with and without subjective cognitive decline (SCD), and in those clinically diagnosed with mild cognitive impairment (MCI) or mild AD. MATERIALS AND METHODS: A convolutional neural network was trained using manually corrected, filter-based segmentations (n = 1000) to automatically segment the PVS in the centrum semiovale from interpolated, coronal T2-weighted magnetic resonance imaging scans (n = 894). These scans were sourced from the national German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study. Convolutional neural network-based segmentations and those performed by a human rater were compared in terms of segmentation volume, identified PVS clusters, as well as Dice score. The comparison revealed good segmentation quality (Pearson correlation coefficient r = 0.70 with P < 0.0001 for PVS volume, detection rate in cluster analysis = 84.3%, and Dice score = 59.0%). Subsequent multivariate linear regression analysis, adjusted for participants' age, was performed to correlate PVS volume with clinical diagnoses, disease progression, cerebrospinal fluid biomarkers, lifestyle factors, and cognitive function. Cognitive function was assessed using the Mini-Mental State Examination, the Comprehensive Neuropsychological Test Battery, and the Cognitive Subscale of the 13-Item Alzheimer's Disease Assessment Scale. RESULTS: Multivariate analysis, adjusted for age, revealed that participants with AD and MCI, but not those with SCD, had significantly higher PVS volumes compared with CU participants without SCD (P = 0.001 for each group). Furthermore, CU participants who developed incident MCI within 4.5 years after the baseline assessment showed significantly higher PVS volumes at baseline compared with those who did not progress to MCI (P = 0.03). Cognitive function was negatively correlated with PVS volume across all participant groups (P ≤ 0.005 for each). No significant correlation was found between PVS volume and any of the following parameters: cerebrospinal fluid biomarkers, sleep quality, body mass index, nicotine consumption, or alcohol abuse. CONCLUSIONS: The very early changes of PVS volume may suggest that alterations in PVS function are involved in the pathophysiology of AD. Overall, the volumetric assessment of centrum semiovale PVS represents a very early imaging biomarker for AD.

A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices.

Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer's disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls (n = 97), individuals with subjective cognitive decline (n = 59), or patients with mild cognitive impairment (n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.

[ViaCogScreen: An Efficient, Valid, and Repeatable Screening Tool for Cognitive Performance Assessment of the Elderly]. / ViaCogScreen: ein zeitökonomisches, valides und wiederholbares Screeningverfahren zum Leistungsmonitoring älterer Menschen.

Given the demographic change with an aging society in Germany, cognitive performance assessment of the elderly is of great importance. The Viacogscreen developed by us is a computer- and web-based brain performance screening for older adults that not only meets the criteria of a measurement instrument, but is also economical and repeatable. The test captures interlocking word list learning with delayed free recall and recognition, semantic word selection and fluidity, phonemic word fluidity and inverted number range, as well as incidental memory, resulting in a total of 17 performance parameters that provide a quick orientation (approximate test duration: 10-12 minutes) regarding the cognitive performance of a test subject. Three performance areas are depicted: executive functions, episodic and semantic memory. The test was standardized for 200 healthy test subjects in 6 different age groups (range: 50-85 years). For the first clinical validation, the test was used in the memory clinics in Bonn and Ulm, where 33 patients with MCI (mild cognitive impairment) and 42 patients with suspected Alzheimer's disease (VAD) were tested. A control group of 42 healthy people of approximately the same age served as the control group. With regard to the cognitive test procedure, all three groups showed significantly different results regarding the overall score (ANOVA F=73.9, p<0.001), executive functions (F=27.6 p<0.001) and semantic memory (F=54.4 p<0.001). Regarding episodic memory, both clinical groups differed significantly from the control group, but not from each other (F=48.7, p<0.001). The Viacogscreen thus produced very good results in its first validation in two memory clinics with regard to differentiation of VAD, and good results with regard to MCI. In addition to use in neurodegenerative diseases, the Viacogscreen is also suitable for other neurological and neuro-oncological diseases, as well as for use in large clinical studies since it enables electronic data collection.

Blood-Based Biomarkers for Early Alzheimer's Disease Diagnosis in Real-World Settings.

As our knowledge about the biology of Alzheimer's disease (AD) expands and we recognize the significance of early intervention for effective treatment, there is a shift in focus toward detecting the disease at an early stage. AD is characterized by the accumulation of misfolded amyloid-ß (Aß) and phosphorylated tau proteins in the brain, leading to the formation of senile plaques and neurofibrillary tangles. While a definitive diagnosis of AD can only be confirmed through autopsy by examining these pathological features, there are now reliable methods available for diagnosing the disease in living individuals. These methods involve analyzing cerebrospinal fluid and using positron emission tomography to accurately assess the presence of Aß and tau proteins. While these diagnostic markers have shown high accuracy in memory-clinic populations, they do have limitations such as the requirement for invasive lumbar puncture or exposure to ionizing radiation. Additionally, they are not easily accessible outside of specialized healthcare settings. Blood-based biomarkers of the core pathological features of AD are being developed, showing promise for less invasive, scalable identification of AD cases in the community. The advantages for the healthcare systems of this development are obvious, but the diagnostic performance of blood-based biomarkers in broader, non-selected populations outside of retrospective analyses and research cohorts still requires further investigation, including the combination with more effective neuropsychological assessments such as digital cognitive test solutions.

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia.

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease.

OBJECTIVES: Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical features increasing AD likelihood (SCD+). METHODS: Amyloid-PET information ([18F]Flutemetamol or [18F]Florbetaben) of individuals with SCD+, mild cognitive impairment (MCI), and AD were retrieved from the AMYPAD-DPMS cohort, a multicenter randomized controlled study. Group classification was based on the recommendations by the SCD-I and NIA-AA working groups. Amyloid PET images were acquired within 8 months after initial screening and processed with AMYPYPE. Amyloid load was based on global Centiloid (CL) values. Educational level was indexed by formal schooling and subsequent higher education in years. Using linear regression analysis, the main effect of education on CL values was tested across the entire cohort, followed by the assessment of an education-by-diagnostic-group interaction (covariates: age, sex, and recruiting memory clinic). To account for influences of non-AD pathology and comorbidities concerning the tested amyloid-education association, we compared white matter hyperintensity (WMH) severity, cardiovascular events, depression, and anxiety history between lower-educated and higher-educated groups within each diagnostic category using the Fisher exact test or χ2 test. Education groups were defined using a median split on education (Md = 13 years) in a subsample of the initial cohort, for whom this information was available. RESULTS: Across the cohort of 212 individuals with SCD+ (M(Age) = 69.17 years, F 42.45%), 258 individuals with MCI (M(Age) = 72.93, F 43.80%), and 195 individuals with dementia (M(Age) = 74.07, F 48.72%), no main effect of education (ß = 0.52, 95% CI -0.30 to 1.58), but a significant education-by-group interaction on CL values, was found (p = 0.024) using linear regression modeling. This interaction was driven by a negative association of education and CL values in the SCD+ group (ß = -0.11, 95% CI -4.85 to -0.21) and a positive association in the MCI group (ß = 0.15, 95% CI 0.79-5.22). No education-dependent differences in terms of WMH severity and comorbidities were found in the subsample (100 cases with SCD+, 97 cases with MCI, 72 cases with dementia). DISCUSSION: Education may represent a factor oppositely modulating subjective awareness in preclinical stages and objective severity of ongoing neuropathologic processes in clinical stages.

European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders.

The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.

Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline.

INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.

MRI or 18F-FDG PET for Brain Age Gap Estimation: Links to Cognition, Pathology, and Alzheimer Disease Progression.

Deviations of brain age from chronologic age, known as the brain age gap (BAG), have been linked to neurodegenerative diseases such as Alzheimer disease (AD). Here, we compare the associations of MRI-derived (atrophy) or 18F-FDG PET-derived (brain metabolism) BAG with cognitive performance, neuropathologic burden, and disease progression in cognitively normal individuals (CNs) and individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Methods: Machine learning pipelines were trained to estimate brain age from 185 matched T1-weighted MRI or 18F-FDG PET scans of CN from the Alzheimer's Disease Neuroimaging Initiative and validated in external test sets from the Open Access of Imaging and German Center for Neurodegenerative Diseases-Longitudinal Cognitive Impairment and Dementia studies. BAG was correlated with measures of cognitive performance and AD neuropathology in CNs, SCD subjects, and MCI subjects. Finally, BAG was compared between cognitively stable and declining individuals and subsequently used to predict disease progression. Results: MRI (mean absolute error, 2.49 y) and 18F-FDG PET (mean absolute error, 2.60 y) both estimated chronologic age well. At the SCD stage, MRI-based BAG correlated significantly with beta-amyloid1-42 (Aß1-42) in cerebrospinal fluid, whereas 18F-FDG PET BAG correlated with memory performance. At the MCI stage, both BAGs were associated with memory and executive function performance and cerebrospinal fluid Aß1-42, but only MRI-derived BAG correlated with phosphorylated-tau181/Aß1-42 Lastly, MRI-estimated BAG predicted MCI-to-AD progression better than 18F-FDG PET-estimated BAG (areas under the curve, 0.73 and 0.60, respectively). Conclusion: Age was reliably estimated from MRI or 18F-FDG PET. MRI BAG reflected cognitive and pathologic markers of AD in SCD and MCI, whereas 18F-FDG PET BAG was sensitive mainly to early cognitive impairment, possibly constituting an independent biomarker of brain age-related changes.

Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia.

Structural and functional changes in cortical and subcortical regions have been reported in behavioral variant frontotemporal dementia (bvFTD), however, a multimodal approach may provide deeper insights into the neural correlates of neuropsychiatric symptoms. In this multicenter study, we measured cortical thickness (CTh) and subcortical volumes to identify structural abnormalities in 37 bvFTD patients, and 37 age- and sex-matched healthy controls. For seed regions with significant structural changes, whole-brain functional connectivity (FC) was examined in a sub-cohort of N = 22 bvFTD and N = 22 matched control subjects to detect complementary alterations in brain network organization. To explore the functional significance of the observed structural and functional deviations, correlations with clinical and neuropsychological outcomes were tested where available. Significantly decreased CTh was observed in the bvFTD group in caudal middle frontal gyrus, left pars opercularis, bilateral superior frontal and bilateral middle temporal gyrus along with subcortical volume reductions in bilateral basal ganglia, thalamus, hippocampus, and amygdala. Resting-state functional magnetic resonance imaging showed decreased FC in bvFTD between: dorsal striatum and left caudal middle frontal gyrus; putamen and fronto-parietal regions; pallidum and cerebellum. Conversely, bvFTD showed increased FC between: left middle temporal gyrus and paracingulate gyrus; caudate nucleus and insula; amygdala and parahippocampal gyrus. Additionally, cortical thickness in caudal, lateral and superior frontal regions as well as caudate nucleus volume correlated negatively with apathy severity scores of the Neuropsychiatry Inventory Questionnaire. In conclusion, multimodal structural and functional imaging indicates that fronto-striatal regions have a considerable influence on the severity of apathy in bvFTD.

[Dementia with Lewy bodies: old and new knowledge - Part 1: clinical aspects and diagnostics]. / Demenz mit Lewy-Körpern: alte und neue Erkenntnisse ­ Teil 1: Klinik und Diagnostik.

BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Patients with DLB often have a poor prognosis, with worse outcomes than patients with Alzheimer's disease in terms of important parameters, such as quality of life, caregiver burden, health-related costs, frequency of hospital and nursing home admissions, shorter time to severe dementia, and lower survival. The DLB is frequently misdiagnosed and often undertreated. Therefore, it is critical to diagnose DLB as early as possible to ensure optimal care and treatment. OBJECTIVE: The aim of this review article is to summarize the main recent findings on diagnostic tools, epidemiology and genetics of DLB. RESULTS: Precise clinical diagnostic criteria exist for DLB that enable an etiologic assignment. Imaging techniques are used as standard in DLB, especially also to exclude non-neurodegenerative causes. In particular, procedures in nuclear medicine have a high diagnostic value. DISCUSSION: The diagnosis is primarily based on clinical symptoms, although the development of in vivo neuroimaging and biomarkers is changing the scope of clinical diagnosis as well as research into this devastating disease.

[Dementia with Lewy bodies: old and new knowledge-Part 2: treatment]. / Demenz mit Lewy-Körpern: alte und neue Erkenntnisse ­ Teil 2: Behandlung.

BACKGROUND: The treatment of patients with dementia with Lewy bodies (DLB) is multifaceted, as motor symptoms, cognitive symptoms, behavioral and psychological symptoms can occur in different constellations. In addition, the use of certain medications is limited (e.g., neuroleptics). OBJECTIVE: To summarize the main recent findings on the treatment of DLB. RESULTS: To date, there is no approved therapeutic option for the treatment of patients with DLB in Germany; moreover, the evidence base for pharmacological and non-pharmacological treatment is sparse. The currently consented treatment options are based on the treatment of motor symptoms in the same way as the treatment of Parkinson's disease and for behavioral symptoms based on the treatment for Alzheimer's disease. DISCUSSION: The treatment of DLB with its various symptoms is difficult and often can only be adequately achieved for the patient in close cooperation with a specialist.

Dementia and comorbidities in primary care: a scoping review.

BACKGROUND: People with dementia (PwD) are known to have more chronic conditions compared to those without dementia, which can impact the clinical presentation of dementia, complicate clinical management and reduce overall quality of life. While primary care providers (PCPs) are integral to dementia care, it is currently unclear how PCPs adapt dementia care practices to account for comorbidities. This scoping review maps recent literature that describes the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities, identifies critical knowledge gaps and proposes potential avenues for future research. METHODS: We searched for peer-reviewed literature published between 2017-2022 in MEDLINE, Cochrane Library, and Scopus using key terms related to dementia, primary care, and comorbidity. The literature was screened for relevance by title-abstract screening and subsequent full-text screening. The prioritized papers were categorized as either 'Risk Assessment and Prevention', 'Screening, Detection, and Diagnosis' or 'Management' and were further labelled as either 'Tools and Technologies', 'Recommendations for Clinical Practice' or 'Programs and Initiatives'. RESULTS: We identified 1,058 unique records in our search and respectively excluded 800 and 230 publications during title-abstract and full-text screening. Twenty-eight articles were included in our review, where ~ 50% describe the development and testing of tools and technologies that use pre-existing conditions to assess dementia risk. Only one publication provides official dementia screening guidelines for PCPs in people with pre-existing conditions. About 30% of the articles discuss managing the care of PwD, where most were anchored around models of multidisciplinary care and mitigating potentially inappropriate prescribing. CONCLUSION: To our knowledge, this is the first scoping review that examines the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities. Given our findings, we recommend that future studies: 1) further validate tools for risk assessment, timely detection and diagnosis that incorporate other health conditions; 2) provide additional guidance into how comorbidities could impact dementia care (including prescribing medication) in primary care settings; 3) incorporate comorbidities into primary care quality indicators for dementia; and 4) explore how to best incorporate dementia and comorbidities into models/frameworks of holistic, person-centred care.

[How Successful is the Participation of People with Mental Illness and Family Members in the Development of Evidence- and Consensus-Based Clinical Practice Guidelines? Results of a Survey in Psychiatry]. / Wie gelingt die Einbindung von Betroffenen- und Angehörigenvertreter:innen in die Entwicklung von evidenz- und konsensbasierten Behandlungsleitlinien? Ergebnisse einer Umfrage im Fachbereich Psychiatrie.

OBJECTIVE: The study examines how successful the participation of people with mental illness and family members is currently in the development of psychiatric guidelines. METHODS: Survey results of N=561 (Response 37%) guideline developers are analyzed. RESULTS: Involvement of affected individuals succeeds more often than that of family members (61% vs. 55%). 68% felt that this participation was central to successful guideline development. 51% perceived discrepancies between empirical evidence and experience perspective. 33-36% perceived a lack of appreciation of experience expertise, 37% an insufficient representation and 46% an inequality in consensus building. 45% did not see barriers effectively removed. CONCLUSION: There remain challenges in the participation of people with mental illness and family members. There is an increasing awareness that their participation is central.

Effects of a mindfulness-based intervention and a health self-management programme on psychological well-being in older adults with subjective cognitive decline: Secondary analyses from the SCD-Well randomised clinical trial.

OBJECTIVES: Older adults with subjective cognitive decline (SCD) recruited from memory clinics have an increased risk of developing dementia and regularly experience reduced psychological well-being related to memory concerns and fear of dementia. Research on improving well-being in SCD is limited and lacks non-pharmacological approaches. We investigated whether mindfulness-based and health education interventions can enhance well-being in SCD. METHODS: The SCD-Well trial (ClinicalTrials.gov: NCT03005652) randomised 147 older adults with SCD to an 8-week caring mindfulness-based approach for seniors (CMBAS) or an active comparator (health self-management programme [HSMP]). Well-being was assessed at baseline, post-intervention, and 6-month post-randomisation using the Psychological Well-being Scale (PWBS), the World Health Organisation's Quality of Life (QoL) Assessment psychological subscale, and composites capturing meditation-based well-being dimensions of awareness, connection, and insight. Mixed effects models were used to assess between- and within-group differences in change. RESULTS: CMBAS was superior to HSMP on changes in connection at post-intervention. Within both groups, PWBS total scores, psychological QoL, and composite scores did not increase. Exploratory analyses indicated increases in PWBS autonomy at post-intervention in both groups. CONCLUSION: Two non-pharmacological interventions were associated with only limited effects on psychological well-being in SCD. Longer intervention studies with waitlist/retest control groups are needed to assess if our findings reflect intervention brevity and/or minimal base rate changes in well-being.

Prevalence of COVID-19 and Psychotropic Drug Treatment in Psychiatric In-patients in Germany in 2020: Results from a Nationwide Pilot Survey.

INTRODUCTION: In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of COVID-19 and an increased mortality have been described. Conversely, observations of lower COVID-19 incidences in psychiatric in-patients suggested protective effects of psychiatric treatment and/or psychotropic drugs against COVID-19. METHODS: A retrospective multi-center study was conducted in 24 German psychiatric university hospitals. Between April and December 2020 (the first and partly second wave of COVID-19), the effects of COVID-19 were assessed on psychiatric in-patient care, the incidence and course of a SARS-CoV-2 infection, and treatment with psychotropic drugs. RESULTS: Patients (n=36,322) were admitted to the hospitals. Mandatory SARS-CoV-2 tests before/during admission were reported by 23 hospitals (95.8%), while 18 (75%) conducted regular testing during the hospital stay. Two hundred thirty-two (0.6%) patients were tested SARS-CoV-2-positive. Thirty-seven (16%) patients were receiving medical treatment for COVID-19 at the psychiatric hospital, ten (4.3%) were transferred to an intermediate/intensive care unit, and three (1.3%) died. The most common prescription for SARS-CoV-2-positive patients was for second-generation antipsychotics (n=79, 28.2%) and antidepressants (SSRIs (n=38, 13.5%), mirtazapine (n=36, 12.9%) and SNRIs (n=29, 10.4%)). DISCUSSION: Contrary to previous studies, our results showed a low number of infections and mortality in SARS-CoV-2-positive psychiatric patients. Several preventive measures seem effective to protect this vulnerable group. Our observations are compatible with the hypothesis of a protective effect of psychotropic drugs against COVID-19 as the overall mortality and need for specific medical treatment was low.

Recruitment of pre-dementia participants: main enrollment barriers in a longitudinal amyloid-PET study.

BACKGROUND: The mismatch between the limited availability versus the high demand of participants who are in the pre-dementia phase of Alzheimer's disease (AD) is a bottleneck for clinical studies in AD. Nevertheless, potential enrollment barriers in the pre-dementia population are relatively under-reported. In a large European longitudinal biomarker study (the AMYPAD-PNHS), we investigated main enrollment barriers in individuals with no or mild symptoms recruited from research and clinical parent cohorts (PCs) of ongoing observational studies. METHODS: Logistic regression was used to predict study refusal based on sex, age, education, global cognition (MMSE), family history of dementia, and number of prior study visits. Study refusal rates and categorized enrollment barriers were compared between PCs using chi-squared tests. RESULTS: 535/1856 (28.8%) of the participants recruited from ongoing studies declined participation in the AMYPAD-PNHS. Only for participants recruited from clinical PCs (n = 243), a higher MMSE-score (ß = - 0.22, OR = 0.80, p < .05), more prior study visits (ß = - 0.93, OR = 0.40, p < .001), and positive family history of dementia (ß = 2.08, OR = 8.02, p < .01) resulted in lower odds on study refusal. General study burden was the main enrollment barrier (36.1%), followed by amyloid-PET related burden (PCresearch = 27.4%, PCclinical = 9.0%, X2 = 10.56, p = .001), and loss of research interest (PCclinical = 46.3%, PCresearch = 16.5%, X2 = 32.34, p < .001). CONCLUSIONS: The enrollment rate for the AMYPAD-PNHS was relatively high, suggesting an advantage of recruitment via ongoing studies. In this observational cohort, study burden reduction and tailored strategies may potentially improve participant enrollment into trial readiness cohorts such as for phase-3 early anti-amyloid intervention trials. The AMYPAD-PNHS (EudraCT: 2018-002277-22) was approved by the ethical review board of the VU Medical Center (VUmc) as the Sponsor site and in every affiliated site.

Machine learning-based classification of Alzheimer's disease and its at-risk states using personality traits, anxiety, and depression.

BACKGROUND: Alzheimer's disease (AD) is often preceded by stages of cognitive impairment, namely subjective cognitive decline (SCD) and mild cognitive impairment (MCI). While cerebrospinal fluid (CSF) biomarkers are established predictors of AD, other non-invasive candidate predictors include personality traits, anxiety, and depression, among others. These predictors offer non-invasive assessment and exhibit changes during AD development and preclinical stages. METHODS: In a cross-sectional design, we comparatively evaluated the predictive value of personality traits (Big Five), geriatric anxiety and depression scores, resting-state functional magnetic resonance imaging activity of the default mode network, apoliprotein E (ApoE) genotype, and CSF biomarkers (tTau, pTau181, Aß42/40 ratio) in a multi-class support vector machine classification. Participants included 189 healthy controls (HC), 338 individuals with SCD, 132 with amnestic MCI, and 74 with mild AD from the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). RESULTS: Mean predictive accuracy across all participant groups was highest when utilizing a combination of personality, depression, and anxiety scores. HC were best predicted by a feature set comprised of depression and anxiety scores and participants with AD were best predicted by a feature set containing CSF biomarkers. Classification of participants with SCD or aMCI was near chance level for all assessed feature sets. CONCLUSION: Our results demonstrate predictive value of personality trait and state scores for AD. Importantly, CSF biomarkers, personality, depression, anxiety, and ApoE genotype show complementary value for classification of AD and its at-risk stages.