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Abstract INTRODUCTION We investigated whether mortality in memory clinic patients changed due to coronavirus disease 2019 (COVID‐19) pandemic. METHODS We included patients from the Amsterdam Dementia Cohort: (1) n = 923 pandemic patients (baseline visit: 2017–2018, follow‐up: until 2021), and (2) n = 830 historical control patients (baseline visit: 2015–2016, follow‐up: until 2019). Groups were well‐balanced. We compared mortality during pandemic with historical control patients using Cox regression. Differences in cause of death between groups were explored using Fisher's exact test. RESULTS Pandemic patients had a higher risk of mortality than historical control patients (hazard ratio [HR] [95% confidence interval {CI}] = 1.34 [1.05–1.70]). Stratified for syndrome diagnosis, the effect remained significant in dementia patients (HR [95% CI] = 1.35 [1.03–1.78]). Excluding patients who died of COVID‐19‐infection, the higher mortality risk in pandemic patients attenuated (HR [95% CI] = 1.24 [0.97–1.58]). Only the difference in cause of death between pandemic patients and historical control patients for death to COVID‐19‐infection (p = 0.001) was observed. CONCLUSION Memory clinic patients had increased mortality risk during COVID‐19 compared to historical control patients, attributable to dementia patients. Highlights We investigated if mortality rates in memory clinic patients changed due to COVID‐19 pandemic. We included patients along the cognitive continuum, including SCD, MCI, and dementia. We used a well‐balanced historical control group. Memory clinic patients had higher risk for mortality during COVID‐19 lockdown. Our results indicate that excess mortality is mainly caused by death to COVID‐19 infection.

Abstract Interpretation of axonal damage biomarker Neurofilament Light chain (NfL) concentrations is difficult due to the lack of age‐specific and disease‐specific reference values. We here developed an interactive interface to support interpretation of NfL results in human body fluids. We used NfL values of 1698 individuals without a neurological disorder, aged 19–85 years, and patients with MS and dementias. Percentile regression estimates per diagnosis populate interactive graphs, alongside NfL background information (available on: https://mybiomarkers.shinyapps.io/Neurofilament). This accessible interface provides reference for interpretation of the individual patient results for clinicians. It showcases an adaptable method to support interpretation of age‐dependent biomarkers in neurology.

Abstract The disease trajectory and healthcare requirements of patients with young‐onset dementia (YOD) differ from those of older patients. Accurate data about YOD is crucial to improve diagnosis and optimize care. PRECODE‐GP aims to set up a prospective national database of patients with YOD to gain insight into the occurrence and characteristics of patients with YOD in memory clinics in the Netherlands. The national database includes data from dementia patients aged

Abstract INTRODUCTION Delay in diagnosis of posterior cortical atrophy (PCA) syndrome is common, and the lack of familiarity with assessment tools for identifying visual cortical dysfunction is a contributing factor. We propose recommendations for the approach to the evaluation of PCA clinical features during the office visit, the neuropsychological evaluation, and the research setting. A recommended screening battery for eye clinics is also proposed. METHODS Recommendations were developed using results from a web‐based survey of members of Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Atypical Alzheimer's Disease Professional Interest Area (PIA), literature review, and consensus by the PCA assessment working party of the Atypical Alzheimer's Disease PIA. RESULTS Survey results revealed robust agreement for assessment tool preferences for PCA features, and many respondents indicated that they reserve assessment tools for use only when PCA is suspected. For some PCA features, curated tools were preferred over validated battery tools, particularly for the office visit. Consensus recommendations superseded survey preferences for two core cognitive features within the 2017 PCA diagnostic criteria. DISCUSSION These consensus recommendations provide an evaluation framework for PCA clinical features and can facilitate timely and accurate recognition and diagnosis of PCA. Broader use of these tools should be sought, and development and validation of novel PCA clinical outcome assessments are needed to improve our understanding of atypical AD and other dementias and support the inclusion of those with PCA in treatment trials.

Abstract Background The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide patients with the desired certainty. Objective To examine, using both quantitative and qualitative methods, uncertainty communicated by memory clinic clinicians in post‐diagnostic testing consultations with patients and their caregivers. Methods First, we identified all uncertainty expressions of 22 clinicians in audiotaped post‐diagnostic testing consultations with 78 patients. Second, we statistically explored relationships between patient/clinician characteristics and uncertainty expressions. Third, the transcribed uncertainty expressions were qualitatively analysed, determining the topic to which they pertained, their source and initiator/elicitor (clinicians/patients/caregivers). Results Within 57/78 (73%) consultations, clinicians expressed in total 115 uncertainties, of which 37% elicited by the patient or caregiver. No apparent relationships were found between patient/clinician characteristics and whether or not, and how often clinicians expressed uncertainty. Uncertainty expressions pertained to ten different topics, most frequently patient's diagnosis and symptom progression. Expressed uncertainty was mostly related to the unpredictability of the future and limits to available knowledge. Discussion and conclusions The majority of clinicians openly discussed the limits of scientific knowledge and diagnostic testing with patients and caregivers in the dementia context. Noticeably, clinicians did not discuss uncertainty in about one quarter of consultations. More evidence is needed on the beneficial and/or harmful effects on patients of discussing uncertainty with them. This knowledge can be used to support clinicians to optimally convey uncertainty and facilitate patients' uncertainty management.

Abstract Introduction Retinal thickness measured with optical coherence tomography has been proposed as a noninvasive biomarker for Alzheimer's disease (AD). We therefore measured retinal thickness in well‐characterized AD and control participants, considering ophthalmological confounders. Methods We included 57 amyloid‐proven AD cases and 85 cognitively normal, amyloid‐negative controls. All subjects underwent retinal thickness measurements with spectral domain optical coherence tomography and an ophthalmological assessment to exclude ocular disease. Results Retinal thickness did not discriminate cases from controls, including stratified analyses for early‐ versus late‐onset AD. We found significant associations between macular thickness and global cortical atrophy [β −0.358; P = .01] and parietal cortical atrophy on magnetic resonance imaging [β −0.371; P < .01] in AD cases. Discussion In this study, representing the largest optical coherence tomography cohort with amyloid‐proven AD cases, we show that retinal thickness does not discriminate AD from controls, despite evident changes on clinical, neuroimaging, and CSF measures, querying the use of retinal thickness measurements as an AD biomarker.

Abstract Introduction We aimed to describe clinician‐patient communication in the diagnostic process of memory clinics, specifically clinician behavior known to facilitate knowledgeable participation of patients during consultations. Methods In this multicenter, observational study, we audio‐recorded routine diagnostic consultations of 41 clinicians and 136 patients/caregivers at eight memory clinics. Patients/caregivers completed surveys after each audiotaped consultation. We used a study‐specific coding scheme to categorize communication behavior. Results Clinicians often provided information on (results of) diagnostic testing. They infrequently invited questions and/or checked understanding. Clinician behavior to involve patients in decision‐making about diagnostic testing was limited. Of note, patients/caregivers rarely expressed their information or involvement preferences. Yet, approximately, one quarter of them would have liked to receive more information. Discussion Involving patients more explicitly by means of shared decision‐making could benefit the quality of care provided in memory clinics because it enables clinicians to attune the diagnostic workup to the individual patient's needs.

Abstract Introduction To construct a prognostic model based on amyloid positron emission tomography (PET) to predict clinical progression in individual patients with mild cognitive impairment (MCI). Methods We included 411 MCI patients from the Alzheimer's Disease Neuroimaging Initiative. Prognostic models were constructed with Cox regression with demographics, magnetic resonance imaging, and/or amyloid PET to predict progression to Alzheimer's disease dementia. The models were validated in the Amsterdam Dementia Cohort. Results The combined model (Harrell's C = 0.82 [0.78–0.86]) was significantly superior to demographics (β = 0.100, P < .001), magnetic resonance imaging (β = 0.037, P = .011), and PET only models (β = 0.053, P = .003).The models can be used to calculate individualized risk, for example, a female MCI patient (age = 60, APOE ε4 positive, Mini‐Mental State Examination = 25, hippocampal volume = 5.8 cm3, amyloid PET positive) has 35% (19–57) risk in one year and 85% (64–97) risk in three years. Model performances in the Amsterdam Dementia Cohort were reasonable. Discussion The present study facilitates the interpretation of an amyloid PET result in the context of a patient's own characteristics and clinical assessment.

Abstract Introduction The retina is a potential source of noninvasive vascular biomarkers for Alzheimer's disease (AD). We assessed retinal microvasculature in well‐characterized AD cases, taking ophthalmological confounders into account. Methods We included 48 amyloid‐positive AD patients and 38 amyloid‐negative cognitively normal control subjects. All participants underwent ophthalmological screening to exclude interfering ocular disease. Using a multimodal approach, we measured retinal vascular parameters, choroidal thickness, macular vascular density, and foveal avascular zone size. Results We found no disease effects on retinal vascular measures (all β′s < |0.15|, all P > .2), adjusted for confounders. Venular tortuosity was inversely associated with Fazekas score in control subjects (β −0.56, P < .01), while vessel density in the outer ring of the macula was inversely associated with Fazekas score in AD cases (β −0.64, P < .01). Discussion In conclusion, retinal vasculature did not discriminate patients with AD from control subjects, despite evident changes on clinical, neuroimaging, and cerebrospinal fluid biomarkers, challenging the use of retinal vasculature measurements as AD biomarker.

Abstract Background Patients often perceive a lumbar puncture (LP) as an invasive procedure. We aimed to evaluate the impact of a 3‐minute educational animation‐video explaining the LP procedure, on patients’ knowledge, uncertainty, anxiety, and post‐LP complications. Methods We included 203 newly referred memory clinic patients, who were randomly assigned to one of three conditions: (1) home viewing of the video, (2) clinic viewing of the video, or (3) control condition (care as usual). Participants completed questionnaires measuring knowledge as information recall, uncertainty, anxiety, and post‐LP complications, the latter when patients underwent an LP procedure (n = 145). Results Viewing the video increased information recall for both home (P

Abstract Background We studied to what degree and at whose initiative 25 informational topics, formerly identified as important, are discussed in diagnostic consultations. Methods Audio recordings of clinician–patient consultations of 71 patients and 32 clinicians, collected in eight Dutch memory clinics, were independently content‐coded by two coders. The coding scheme encompassed 25 informational topics. Results Approximately half (Mdn = 12) of the 25 topics were discussed per patient during the diagnostic process, with a higher frequency among individuals receiving a dementia diagnosis (Mdn = 14) compared to others (Mdn = 11). Individual topics ranged from being discussed with 2/71 (3%) to 70/71 (99%) of patients. Patients and/or care partners rarely initiated topic discussion (10%). When they did, they often enquired about one of the least frequently addressed topics. Conclusion Most patients received information on approximately half of the important informational topics. Providing the topic list to patients and care partners beforehand could allow consultation preparation and stimulate participation.

Abstract Introduction We compared the automated Elecsys and manual Innotest immunoassays for cerebrospinal fluid (CSF) Alzheimer's disease biomarkers in a multicenter diagnostic setting. Methods We collected CSF samples from 137 participants in eight local memory clinics. Amyloid β(1–42) (Aβ42), total tau (t‐tau), and phosphorylated tau (p‐tau) were centrally analyzed with Innotest and Elecsys assays. Concordances between methods were assessed. Results Biomarker results strongly correlated between assays with Spearman's ρ 0.94 for Aβ42, 0.98 for t‐tau, and 0.98 for p‐tau. Using Gaussian mixture modeling, cohort‐specific cut‐points were estimated at 1092 pg/mL for Aβ42, 235 pg/mL for t‐tau, and 24 pg/mL for p‐tau. We found an excellent concordance of biomarker abnormality between assays of 97% for Aβ42 and 96% for both t‐tau and p‐tau. Discussion The high concordances between Elecsys and Innotest in this nonacademic, multicenter cohort support the use of Elecsys for CSF Alzheimer's disease diagnostics and allow conversion of results between methods.

Abstract Introduction The retina may reflect Alzheimer's disease (AD) neuropathological changes and is easily visualized with optical coherence tomography (OCT). Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid‐positive early‐onset AD (EOAD) patients and amyloid‐negative controls. Methods We measured macular thickness and peripapillary retinal nerve fiber layer thickness with OCT in 15 EOAD patients and 15 controls and correlated retinal thickness to visual rating scores for atrophy on magnetic resonance imaging. Results Total macular thickness correlated to parietal cortical atrophy in both groups (Spearman ρ −0.603, P = .001). Macular and peripapillary retinal nerve fiber layer thicknesses were not significantly decreased in EOAD compared to controls. Discussion Retinal thickness does not discriminate EOAD from controls but is correlated to parietal cortical atrophy in both groups. These findings may suggest reflection of cerebral cortical changes in the retina, independent of amyloid.

Abstract A lumbar puncture (LP) is performed to obtain cerebrospinal fluid. It is implemented in the clinic on a routine basis to aid the diagnosis of neurologic diseases. This paper accompanies an informative lumbar puncture video that shows the lumbar puncture procedure as routinely performed in the VUmc Alzheimer center based on the consensus guidelines by Engelborghs et al.