Gunhild Waldemar

Introduction: The Brief Assessment of Impaired Cognition (BASIC), and the Brief Assessment of Impaired Cognition Questionnaire (BASIC-Q) are new case-finding tools for cognitive impairment and dementia which are increasingly being used in clinical settings as alternatives to the Mini-Mental State Examination (MMSE). The objective of this study was to develop bi-directional crosswalk tables for conversion between the three instruments for patients 60 years and older. Methods: Patients from memory clinics and general practice ≥ 60 years of age who completed assessment with BASIC, BASIC-Q, and MMSE were included. The equipercentile equating method with log-linear pre-smoothing of data was applied to create conversion tables between instruments. Results: A total of 394 patients completed assessment with BASIC and MMSE, 355 of which also completed BASIC-Q. We present bi-directional conversion tables between the three instruments. Conclusion: The study presents bi-directional crosswalks between BASIC, BASIC-Q and MMSE enabling comparison and synthesis of test results, facilitating communication between clinicians, and potentially helping to inform clinical and policy decision making.

Introduction: Symptoms of Alzheimer’s disease can emerge years before diagnosis, but detailed temporal mapping of morbidity and medication use in the prodromal period is lacking. Methods: We conducted a nationwide retrospective, incidence density-matched nested case–control study including individuals diagnosed with late-onset Alzheimer’s disease in Danish memory clinics from 2016 to 2022 and cognitively healthy matched controls. Exposures were primary and secondary discharge diagnoses from hospital contacts, and redeemed prescriptions. Results: A total of 19,102 patients and 57,306 matched controls were included. At 10 years before diagnosis, individuals who later developed late-onset Alzheimer’s disease had more mental health and behavioral diagnoses and increased use of psychopharmaceuticals, as well as more injuries and hospital contacts for non-specific symptoms. During the five years and one-year preceding diagnosis, morbidity increased across multiple diagnostic categories, while most medication categories decreased. Conclusion: Our findings suggest that prodromal late-onset Alzheimer’s disease is characterized by gradual accumulation of morbidity, with injuries and neuropsychiatric symptoms as the most persistent. This knowledge can guide future hypothesis-driven studies towards better characterization of the prodromal phase that may improve early detection, reduce the burden of unexplained symptoms experienced by patients and their caregivers, and support clinicians facing diagnostic uncertainty.

People with dementia often need comprehensive support, depending on the stage of the disease, from both family members and healthcare professionals. Caring for a person with dementia can be stressful and impact the caregiver's health and wellbeing. Studies show that family caregivers of people with dementia frequently experience stress, depression, and reduced quality of life. We aimed to assess the association between the psychosocial intervention (DemTool) and caregiver wellbeing and quality of life among family caregivers of people with dementia. DemTool trial was a pragmatic, cluster-controlled trial. The intervention was delivered by primary care dementia coordinators across 30 Danish municipalities from 2020 to 2023, with 15 serving as the intervention group and 15 as treatment as usual. The primary outcome measures were the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and the European Quality of Life Visual Analog Scale (EQ VAS). Both measures were completed at baseline and follow-up, alongside secondary quality of life outcomes. To estimate group differences in primary and secondary outcomes, we applied analysis of variance (ANOVA) and analysis of covariance (ANCOVA). A total of 245 family caregivers were included in the study (181 in the intervention group and 64 in the treatment-as-usual group). Most participants were females caring for a spouse. Baseline scores for caregiver wellbeing and quality of life were similar across groups. The DemTool intervention was associated with a significant between-group difference in change from baseline in caregiver-related quality of life as measured by the Carer Experience Scale (CES), favoring the intervention. This was evident in the analysis adjusted for baseline scores (p = 0.05) and remained significant when further adjusting for caregiver-related covariates (p = 0.02). No statistically significant between-group differences were observed for the remaining wellbeing and quality-of-life outcomes. No effects of DemTool were found on traditional health-related quality-of-life outcomes. However, a positive association was found between the intervention and the CES, underlining the importance of selecting outcomes that are directly related to the targeted effects of the intervention. The study protocol was registered in the ClinicalTrials.gov system, registration number: NCT07355829.

Epileptiform discharges in Alzheimer’s disease (AD) and Lewy body dementia (DLB) may be associated with cognitive decline. Iron accumulation has been implicated in neurodegenerative processes; however, its relationship to epileptiform discharges remains unknown. In addition, the relationship between iron deposition, structural brain changes, and epileptiform discharges remains unclear. The objective is to investigate whether iron deposition and structural brain atrophy are associated with epileptiform discharges in patients with AD, DLB, and healthy controls (HCs). A total of 25 patients with AD, 10 patients with DLB, and 15 HCs were included in the analysis. The participants underwent MRI including quantitative susceptibility mapping (QSM) and structural T1-weighted imaging. We examined the four regions of interest, which are tied to iron deposition and AD pathology. Ear-EEG recordings were used to quantify spike frequency (epileptiform discharges/24 h). No significant group differences were found for susceptibility across regions. Susceptibility was not associated with spike frequency. Patients with AD exhibited significant hippocampal atrophy. Higher hippocampal volume was associated with lower spike rates in adjusted models. Susceptibility and hippocampal volume were associated, and in a multilinear model with age, hippocampal volume accounted for a larger proportion of the explained variance. This study found no evidence linking iron deposition to epileptiform discharges in AD or DLB. Instead, hippocampal atrophy appears more strongly associated with epileptiform discharges, which could indicate that the underlying pathological processes rather than iron are the primary driving factor for epileptiform discharges.

Background: Evidence on the prevalence and nature of hearing impairments among patients with Alzheimer's disease and other types of dementia is limited and inconsistent. Objective: The objective of this study was to compare the proportion of individuals with hearing loss and the severity of hearing impairments in peripheral hearing and speech perception in noise of patients with mild cognitive impairment (MCI) and cognitively intact older adults. Methods: Participants included 40 patients with MCI recruited from a memory clinic and 60 community-dwelling cognitively intact older adults (Clinical Dementia Rating Score of 0 and Mini-Mental State Examination ≥ 26). All participants were assessed with pure-tone audiometry and a speech-in-noise test, and with cognitive tests tapping memory, processing speed, executive functions, attention, and language. Results: No significant difference was found in the proportion of individuals with peripheral hearing loss among patients with MCI and cognitively intact older adults (77.5% and 60%, respectively). Speech-in-noise did not differ between the groups either, not even when accounting for aided hearing in those participants that wore hearing aids in their daily life. About one third of patients with MCI did not perceive hearing problems, despite having objectively measured hearing loss. However, this proportion did not differ significantly from the group of cognitively intact older adults. Conclusions: Despite differences in cognitive status, this study did not show significant differences between the groups on measures of peripheral hearing, speech-in-noise, and subjective complaints of hearing when comparing memory clinic patients with cognitively intact older adults.

Background: The Carer Experience Scale (CES) measures the caring experience, focusing on caregiver-related quality of life (QoL) rather than health-related QoL. We aimed to validate the Danish language version of CES in family caregivers of people with dementia in Denmark by assessing CES discriminative and convergent validity. Further, we aimed to establish the internal consistency and test-retest reliability of CES. Methods: A baseline questionnaire from the Danish DemTool intervention trial, including CES and five other measures of QoL and wellbeing was completed by 375 family caregivers of people with dementia. Discriminative validity was assessed by the ability of CES to discriminate between different caring contexts and levels of caregiver strain, as determined by Mann–Whitney U and Kruskal–Wallis H tests. Convergent validity was assessed by analyzing correlations using Spearman’s rank correlation coefficients between the CES index and domain scores, and the 5-level EQ-5D version (EQ-5D-5L), European Quality of life visual analog scale (EQ VAS), Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D), World Health Organization Wellbeing Index (WHO-5), and the University of California, Los Angeles Three-Item Loneliness Scale (UCLA 3-item). Internal consistency was assessed using Cronbach’s α and test-retest reliability was assessed using intraclass correlation coefficient (ICC) between two different time points. Results: The CES effectively distinguished between different levels of caregiver strain. Further, the CES was not affected by different caregiver and care recipient characteristics. Supporting convergent validity, the CES index was moderately correlated with NPI-D (ρ=-0.42), WHO-5 (ρ = 0.44), and UCLA 3-item (ρ=-0.40). The CES index was weakly correlated with EQ-5D-5L (ρ = 0.27), and EQ-VAS (ρ = 0.26). The CES showed low internal consistency (α = 0.53), but high test-retest reliability (ICC = 0.76). Conclusion: The Danish version of CES demonstrated discriminative validity and acceptable psychometric properties, providing further evidence for its use in family caregivers of people with dementia.

The Copenhagen Memory Clinic was established in 1995 and since 2007 a new national center for research and education was established, together forming the Danish Dementia Research Centre (DDRC). Our research and innovation programs have continuously been informed by clinical experience and inspired by the needs of our patients. The link between patient care, research, and education forming together a comprehensive dementia center is therefore of crucial importance. In this review, we present an overview of the clinical program at the Copenhagen Memory Clinic, currently receiving 2.000 new referrals per year. We also present the Copenhagen Memory Clinic Cohort and the associated biobank, as well as clinical, translational and epidemiological research programs performed at DDRC during the past 30 years. Funded in part by the Danish Ministry of Health, our national outreach, professional networks and educational programs are also outlined. From its inception and onwards the primary focus of the DDRC has been with the patients, aiming to continuously improve our clinical service based on research and innovation and to improve the quality of care nationwide. We welcome requests for collaboration on research, innovation and education from international colleagues and research centers.

Background: Opioid use is frequent among older people with dementia. Opioid use has been associated with excess mortality in the general population, but whether this also applies to older people with dementia is unknown. Objective: Investigate if new opioid use compared with no use was associated with excess mortality in older people with dementia. Methods: Matched cohort study using Danish nationwide registries including all residents (age 65+) diagnosed with dementia (including Alzheimer's disease) between 2008–2018. Exposure was defined as first opioid prescription after dementia diagnosis (1 year washout before). Persons exposed to opioids were matched with up to two unexposed persons on age and sex. Outcome was all-cause mortality within 180 days after exposure. Cox proportional hazards models compared rates of death and adjusted for potential confounders. Results: Forty-two percent (31,619/75,471) of older people with dementia initiated a prescription for an opioid after dementia diagnosis. 31,619 exposed persons were matched to 63,235 unexposed. Among the exposed, 8540 (27%) died within 180 days after initiating their first opioid prescription compared with 3803 (6.01%) of the unexposed, yielding a 5-fold excess mortality risk (adjusted Hazard ratio: 5.06 (95% CI, 4.86–5.29)). Transdermal fentanyl use was associated with an 8-fold excess mortality risk (8.26 (7.18–9.51)). Conclusions: Opioid use was associated with excess mortality, which may be due to the opioid, the indication or both. This observation calls for further research into the links between opioid use and excess mortality in elderly with dementia as it could have important implications for patient safety.

Background: The pursuit of accurate biomarkers for early detection and disease monitoring of Alzheimer’s disease (AD) has driven a growing interest in digital biomarkers. We aimed to map the research landscape of digital biomarkers in early AD obtained with wearable or portable digital health technologies (DHTs). Methods: In our scoping review, we included original research on portable or wearable DHTs where digital biomarkers were measured in populations of early AD (mild cognitive impairment (MCI) or mild dementia). We searched MEDLINE, Web of Science and EMBASE with a wide search strategy with independent review and data extraction by two review team members and charted data in tabular/graphical form. Results: After deduplication and screening of 8 893 records, we included 109 studies describing a wide array of wearable or portable obtained digital biomarkers. The study population consisted of 3 019 individuals with MCI due to AD (54% female, weighted mean age 73 years), and 1 942 individuals with mild AD (55% female, weighted mean age 73 years). The most studied biomarkers were rest/activity (39%), speech (17%), and gait (14%), with most studies focusing on one domain. Few studies reported outcomes associated with diagnosis (16%) and prognosis (3%). Conclusion: We identified a growing evidence base investigating digital biomarkers in early AD. There is a paucity of studies examining diagnostic and prognostic properties, representing a knowledge gap. This overview may help to guide future research efforts to bridge the gap between the development and clinical implementation of digital biomarkers in early Alzheimer’s disease.

Introduction: People with dementia have an increased risk for infection‐related complications, which may be mitigated by common vaccinations. The aim was to investigate the association between influenza vaccination and the rates of all‐cause and influenza‐related hospitalizations and deaths among older adults with dementia. Methods: We followed all Danish residents with dementia aged 65 and above from September 1, 2002, to August 31, 2018. Dementia was defined from records in the Danish national registries (positive predictive value 85.8%). People with dementia were identified on September 1 of each year. On this date, vaccination status was also reset, and the status of covariates was assessed. We used proportional hazard Cox regression to compare rates of all‐cause hospitalization, hospitalization with a respiratory infection, hospitalization with influenza or pneumonia, and all‐cause mortality for vaccinated and unvaccinated. Results: Across the entire study period, we included 134,002 people with dementia. Rates of hospitalization were 9%–10% lower, and the mortality rate 9% lower, for vaccinated compared to unvaccinated among people with dementia. Discussion: Influenza vaccination was associated with lower rates of hospitalization and mortality among people with dementia. Further exploration of the preventive potential of influenza vaccination among people with dementia is important for shaping interventions in this vulnerable group.