Are age-related biomarkers of dementia risk accelerated by low educational attainment?

Background: Low education significantly elevates dementia risk but it is not clear whether this is through chronic systemic inflammation, early-onset dementia pathology, or other factors. This project compares biomarkers of inflammation and dementia pathology in a young-old and older cohort. Due to significantly lower education in the young-old cohort, we hypothesized evidence of similar or higher biomarker levels in the young-old cohort compared to the older cohort. Methods: Blood samples were used to measure pro-inflammatory cytokines (C-reactive protein (CRP), tumor necrosis factor (TNF interleukin (IL)-6, and IL-1 anti-inflammatory cytokines (IL-10 and IL-1RA), and the brain biomarkers phosphorylated tau (p-tau) and neurofilament light (NfL). Inflammatory markers were measured at the Considine Lab at the Indiana University School of Medicine using ELISA assays while p-tau and NfL were measured with Simoa assays at the Quanterix lab in Massachusetts. We used the natural logarithm of all biomarker variables to address skewed data. Linear regression was used to investigate race- and gender-adjusted differences in the biomarkers. Results: The young-old cohort (N=42) has a mean age of 62.4, 69.1% are female, and 78.6% are non-Hispanic black (NHB), while the older cohort (N=60) has a mean age of 80.3, 60% are female, and 20% are NHB. Median education in the young-old cohort is 12 vs 16 in the older cohort. Adjusted models showed higher mean CRP (p=0.004) and lower mean IL-10 (p<0.001) in the young-old cohort. TNF- (p <0.001), IL-6 (p=0.021), and IL-1(p=0.017), P-tau (p=0.003), and NfL (p<0.001) were all higher in the older cohort. Conclusion: We found partial support of our hypothesis in that the younger, low education cohort had higher mean CRP and lower mean IL-10 (anti-inflammatory). However, brain biomarkers were higher in the older cohort. More research will be needed to determine if and how low education elevates ADRD risk through systemic inflammation.

Added diagnostic accuracy after [18F]flutemetamol PET scanning in young patients with dementia in an academic memory clinic setting

ABSTRACTIntroductionA timely diagnosis of Alzheimer’s Disease (AD) in an early stage of dementia is important to support timely access to treatment, advice, and care. The aim of this study was to estimate the diagnostic accuracy of [18F]flutemetamol PET in addition to the usual diagnostic workup for the diagnosis of AD in a memory clinic population with young onset dementia by means of a panel reference-based etiology diagnosis.Methodsin an academic memory clinic early onset dementia cohort (n=211) the nosological diagnosis was set by usual diagnostic workup and after including [18F]flutemetamol amyloid PET in a stepwise approach. To assess the change in proportion correctly diagnosed, the diagnosis with and without [18F]flutemetamol PET was related to a panel-based reference standard, serving as gold standard, consisting of 3 neurologists who relied on available clinical information over 2-year follow-up (n=152; blinded for PET).ResultsThe panel majority nosology was set as a reference diagnosis in 122 participants, leaving 30 (20%) participants with no majority reached. In 107 (88%) cases post-PET was in line with the reference, and in 103 (84%) the pre-PET diagnosis was in line with the reference. The difference was 3.3% (95% CI -3.5% to 10.1%; p=0.424).Discussion[18F]flutemetamol PET did not significantly improve the diagnostic accuracy in young patients with dementia in an academic memory clinic setting. The secondary analyses provided several indications for future research in a narrower subsample of persons with (very) high diagnostic uncertainty and to assess patient relevant health outcomes.

Innovations on Dementia Advocacy among Students of a Medical University in Taiwan

In 2017, Taiwan established Dementia Action Plans 2.0 to respond to the World Health Organization's call to increase dementia awareness and support for dementia carers. However, efforts have not yet been made to educate and increase dementia literacy on the younger generations. This paper addressed the outcomes to increase knowledge and information about dementia and caregiver resources to university students. 93 students participated in a two-day workshop on dementia literacy, followed by two months of advocacy in Taichung City, Taiwan. Students were divided into 14 advocacy groups and the outcome reports were categorized qualitatively using content analysis. The results showed that students were from nine departments and over one-quarter having a dementia loved one in the family. Four innovative categories were developed, including (1) dementia literacy for students and the public; (2) dementia friendly action plans; (3) dementia caregiver’s advocacy and (4) reducing dementia stereotypes. Highlights included students using social media to promote dementia literacy, face-to-face experiences to inform public education, dementia education on early onset dementia and using diverse bio-psycho-social angels to evaluate dementia. Students expanded advocacy to many social media, innovations and target areas, including Facebook, Instagram, Google spreadsheet, stickers, postcards, illustration of children’s books and public announcement. This paper revealed that younger generations used many advocacy methods that were thinking outside of the box. In conclusion, dementia is no longer an elder’s business but young adults can bring technological, inter-generational and cultural innovations into fulfilling the goals of Dementia Global Action Plans.

Living With Early-Onset Dementia in China: Through a Person-Centered Care Lens

We conducted semi-structured interviews with 35 dyads of persons with early-onset dementia (EOD) and their primary informal care partners to explore their dyadic experiences of living EOD in Shanghai, China. Many of them are in their 50s and still need to make familial, financial, and social commitments. They experienced significant disruptions of their "normal" family life and family dynamics, social stigma, and felt marginalized when there was very limited age-appropriate support for them. During COVID-19 pandemic, many persons with EDO and their care partners had decreased social networking opportunities, physical exercises and experienced an increased level of social isolation. The pandemic further complicated their family dynamics, relationships, and communications. Care partners used their strengths to adaptively deal with multiple challenges, cope with the stress, social isolation, and normalize their family life by facilitating collaborative work with persons with EOD.

Employers ’ Response to Workers With Progressive Cognitive Impairment: A Review of Policy in Canada

Longer lifespans, the gig economy, eligibility for government pensions, and more testing for age-related cognitive changes, increase the potential for workers developing mild cognitive impairment and/or early onset dementia (MCI|EOD) “on the job”. This critical analysis assesses Canada’s policy environment for employers when employees are diagnosed with MCI|EOD. Our search for policy literature included: a scoping review of academic literature involving Canadian-focused articles, and countries where novel or innovative policy had been evaluated and published; a search for Canadian court judgements and tribunal decisions; and a grey literature search in both Canadian and international sources, as innovation will often happen “at the margin” and updated policy may take years to be enacted and formalized. We used participatory research to obtain feedback from a broad group of stakeholders including employers, industry, professional organizations, and government, as well as people living with MCI/dementia, to ensure outputs were reflective of current policy. We found that: 1) Canadian federally-regulated employers are governed by similar Acts & Codes as the provinces and territories, with some notable exceptions, 2) Disability discrimination and accommodation case law in Canada is settled, however there are few cognitive impairment cases to provide specific guidance, 3) Scant empirical research in the scientific literature addresses policy that incents employers to build workspaces for employees with MCI|EOD that help them stay on the job longer. We conclude that engaging with employers to better understand their needs will help policy-makers to support them build workspaces that encourage productive engagement of all workers.

Employers’ Response to Workers With Progressive Cognitive Impairment: A Systematic Literature Review

An aging workforce increases the risk of workers experiencing cognitive decline that may lead to a diagnosis of mild cognitive impairment or early onset dementia (MCI|EOD) while still employed. This systematic review explores the use of technologies (defined as any methods, processes, software, hardware or equipment) deployed by employers to accommodate, or build sustainable workspaces for, workers diagnosed with MCI|EOD. After screening 3,860 titles/abstracts and 67 full text reviews, we identified and analyzed eight articles that met our inclusion criteria. We found that: 1) The existing literature almost exclusively focuses on employees’ perspectives on the quality of work life when diagnosed with MCI|EOD, 2) Negative workspace culture toward employees’ cognitive decline, and the variability of disease onset and progression, may account for low employer awareness, 3) Employer responses focus on mitigation of risk associated with workers’ impairment. While this review demonstrates there is scant research exploring employers’ perspectives on employees diagnosed with MCI|EOD, there is even less that explores technologies designed to specifically address employers’ needs and challenges. Technology will increasingly facilitate early identification of progressive neuro-cognitive disorders, and tools to help employers respond to an employee’s MCI|EOD disclosure as a disability accommodation rather than a terminal performance management challenge. Empathic research, that engages organizations in the process of understanding the value of affordable, employer-side technologies that help build diverse, sustainable, productive workspaces is critical to a foundational understanding of our aging workforce and accommodating workers who develop MCI|EOD while still employed.

Human Induced Pluripotent Stem Cell Models of Frontotemporal Dementia With Tau Pathology

Neurodegenerative dementias are the most common group of neurodegenerative diseases affecting more than 40 million people worldwide. One of these diseases is frontotemporal dementia (FTD), an early onset dementia and one of the leading causes of dementia in people under the age of 60. FTD is a heterogeneous group of neurodegenerative disorders with pathological accumulation of particular proteins in neurons and glial cells including the microtubule-associated protein tau, which is deposited in its hyperphosphorylated form in about half of all patients with FTD. As for other patients with dementia, there is currently no cure for patients with FTD and thus several lines of research focus on the characterization of underlying pathogenic mechanisms with the goal to identify therapeutic targets. In this review, we provide an overview of reported disease phenotypes in induced pluripotent stem cell (iPSC)-derived neurons and glial cells from patients with tau-associated FTD with the aim to highlight recent progress in this fast-moving field of iPSC disease modeling. We put a particular focus on genetic forms of the disease that are linked to mutations in the gene encoding tau and summarize mutation-associated changes in FTD patient cells related to tau splicing and tau phosphorylation, microtubule function and cell metabolism as well as calcium homeostasis and cellular stress. In addition, we discuss challenges and limitations but also opportunities using differentiated patient-derived iPSCs for disease modeling and biomedical research on neurodegenerative diseases including FTD.