Capturing Usability Problems for People Living With Dementia by Applying the DEMIGNED Principles in Usability Evaluation Methods: Mixed Methods Study.

BACKGROUND: Dementia-related impairments can cause complex barriers to access, use, and adopt digital health technologies (DHTs). These barriers can contribute to digital health inequities. Therefore, literature-based design principles called DEMIGNED have been developed to support the design and evaluation of DHTs for this rapidly increasing population. OBJECTIVE: This study aims to apply the DEMIGNED principles in usability evaluation methods to (1) capture usability problems on a mobile website providing information resources for people visiting a memory clinic, including those living with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia, and (2) investigate the realness of usability problems captured by the DEMIGNED principles in expert testing, specifically for mobile websites that act as a means of providing DHTs. METHODS: First, a heuristic evaluation was conducted, with the DEMIGNED principles serving as domain-specific guidelines, with 3 double experts (experienced in both usability and dementia) and 2 usability engineering experts. Second, think-aloud sessions were conducted with patients visiting a memory clinic who were living with SCD, MCI, or dementia. RESULTS: The heuristic evaluation resulted in 36 unique usability problems. A representative sample of 7 people visiting a memory clinic participated in a think-aloud session, including 4 (57%) with SCD, 1 (14%) with MCI, and 2 (29%) with dementia. The analysis of the think-aloud sessions revealed 181 encounters with usability problems. Of these encounters, 144 (79.6%) could be mapped to 18 usability problems identified in the heuristic evaluation. The remaining 37 (20.4%) encounters from the user testing revealed another 10 unique usability problems. Usability problems frequently described in the think-aloud sessions encompassed difficulties with using the search function, discrepancies between the user's expectations and the content organization, the need for scrolling, information overload, and unclear system feedback. CONCLUSIONS: By applying the DEMIGNED principles in expert testing, evaluators were able to capture 79.6% (144/181) of all usability problem encounters in the user testing of a mobile website for people visiting a memory clinic, including people living with dementia. Regarding unique usability problems, 50% (18/36) of the unique usability problems identified during the heuristic evaluation were captured by the user-testing sessions. Future research should look into the applicability of the DEMIGNED principles to other digital health functionalities to increase the accessibility of digital health and decrease digital health inequity for this complex and rapidly increasing population.

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease.

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-ß precursor protein processing, amyloid-ß aggregation, lipid metabolism and microglial function in AD.

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture.

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.

Hallucinations and other psychotic experiences across diagnoses: A comparison of phenomenological features.

Although psychotic experiences are prevalent across many psychiatric, neurological, and medical disorders, investigation of these symptoms has largely been restricted to diagnostic categories. This study aims to examine phenomenological similarities and differences across a range of diagnoses. We assessed frequency, severity and phenomenology of psychotic experiences in 350 outpatients including; participants with schizophrenia spectrum disorders, hearing impairment, Parkinson's disease, Lewy Body Dementia, Alzheimer's disease, visual impairment, posttraumatic stress disorder, borderline personality disorder, and participants with recent major surgery. Psychotic phenomena were explored between these groups using the Questionnaire for Psychotic Experiences (QPE). Participants with major psychiatric disorders reported a combination of several psychotic experiences, and more severe experiences compared to all other disorders. Participants with recent major surgery or visual impairment experienced isolated visual hallucinations. Participants with hearing impairment reported isolated auditory hallucinations, whereas the neurodegenerative disorders reported visual hallucinations, occasionally in combination with hallucinations in another modality or delusions. The phenomenology between neurodegenerative disorders, and within major psychiatric disorders showed many similarities. Our findings indicate that the phenomenology of psychotic experiences is not diagnosis specific, but may rather point to the existence of various subtypes across diagnoses. These subtypes could have a different underlying etiology requiring specific treatment.

A comprehensive screening of copy number variability in dementia with Lewy bodies.

The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk.

Pre-operative inflammatory markers and the risk of postoperative delirium in elderly patients.

OBJECTIVE: Pathophysiological mechanisms leading to delirium are not clear. Age is a known risk factor and hypothesised to be accompanied by a low-grade inflammatory state. Previous studies have shown an association between delirium and circulating proinflammatory markers in acutely ill and postoperative patients. In light of the ageing/inflammation theory, we investigated the association of these markers with delirium in not acutely ill, elderly patients. METHODS: In a prospective nested case-control study levels of C-reactive protein (CRP), interleukin 6 (Il-6), insulin growth factor 1 (IGF-1) were measured pre-operatively in elderly patients admitted for hip-surgery. These levels were compared between patients who later developed a post-operative delirium and patients who did not. Patients were matched for age and disease severity. RESULTS: Eighteen patients who developed delirium post-operatively were matched with 50 controls. Median APACHE-scores were below 16 in both groups. Pre-operative serum concentrations of CRP, Il-6 and IGF-1 did not differ between groups. IL-6 levels were associated with a measure of cognitive impairment. CONCLUSION: In the present study no relationship was found between levels of pre-operative circulating pro-inflammatory markers and post-operative delirium in elderly patients, who were free from acute or severe disease.