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SummaryHere we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality of human microglia-like cells (iMGLs). We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac. The iMGLs express microglial signature genes and respond to ADP with intracellular Ca2+ release distinguishing them from macrophages. Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality, whereas PSEN1ΔE9 and APPswe mutations trigger minor alterations. The APOE4 genotype impairs phagocytosis, migration, and metabolic activity of iMGLs but exacerbates their cytokine secretion. This indicates that APOE4 iMGLs are fundamentally unable to mount normal microglial functionality in AD.

The association between level of educational attainment and cognitive performance is well studied. People with higher education perform better across a broad range of cognitive tasks. However, there is uncertainty as to whether education moderates the trajectory of age‐related cognitive decline. This review paper addresses the potential link between education and age‐related cognitive decline by evaluating relevant research published since 2000. Studies reporting data on education and its association with the rate of cognitive decline across various cognitive domains were reviewed. A total of 10 studies were identified with a mean follow‐up period of 7.6 years; each contained a population‐based, non‐demented sample. In the majority of studies, results showed that education did not moderate age‐associated cognitive decline. The few studies that did find an association between education and decline in specific cognitive functions should be interpreted with caution because of methodological issues. The literature reveals little consistent evidence that normal age‐related cognitive decline is moderated by education attainment. This supports a passive theory of cognitive reserve: people with a higher level of education will continue to perform at a higher level of cognitive functioning than their lower educated peers, which may delay the onset of impairment in the future.

BackgroundTo ensure carers of people with dementia receive support, community services increasingly use measures of caregiver (carer) burden to assess for unmet need. This study used Bradshaw's taxonomy of need to explore the link between measures of carer burden (normative need), service use (expressed need), and carer's stated need (felt need).MethodsThis mixed method exploratory study compared measures of carer burden with community services received and unmet needs, for 20 community-dwelling carer/care-recipient pairs.ResultsA simple one-item measure of carers' felt need for more services was significantly related to carer stress as measured on the GHQ-30. Qualitative data showed that there are many potential stressors for carers, other than those related to the care-giving role. We found a statistically significant rank correlation (p = 0.01) between carer's use of in-home respite and the care-recipient's cognitive and functional status which is likely to have been related to increased requirement for carer vigilance, effort and the isolation of spouse carers. Otherwise, there were no statistically significant relationships between carer burden or stress and level of service provision.ConclusionWhen carers are stressed or depressed, they can recognise that they would like more help from services, even if measures of carer burden and care recipient status do not clearly indicate unmet service needs. A question designed to elicit carer' felt need may be a better indicator of service need, and a red flag for recognising growing stress in carers of people with dementia. Assessment of service needs should recognise the fallibility of carer burden measures, given that carer stress may not only come from caring for someone with dementia, but can be significantly compounded by other life situations.

We have investigated alterations in myelin associated with Abeta plaques, a major pathological hallmark of Alzheimer's disease (AD), in human tissue and relevant transgenic mice models. Using quantitative morphological techniques, we determined that fibrillar Abeta pathology in the grey matter of the neocortex was associated with focal demyelination in human presenilin-1 familial, sporadic and preclinical AD cases, as well as in two mouse transgenic models of AD, compared with age-matched control tissue. This demyelination was most pronounced at the core of Abeta plaques. Furthermore, we found a focal loss of oligodendrocytes in sporadic and preclinical AD cases associated with Abeta plaque cores. In human and transgenic mice alike, plaque-free neocortical regions showed no significant demyelination or oligodendrocyte loss compared with controls. Dystrophic neurites associated with the plaques were also demyelinated. We suggest that such plaque-associated focal demyelination of the cortical grey matter might impair cortical processing, and may also be associated with aberrant axonal sprouting that underlies dystrophic neurite formation.

BackgroundThe completion rates for Massive Open Online Courses (MOOCs) generally are low (5-10%) and have been reported to favour participants with higher (typically tertiary-level) education. Despite these factors, the flexible learning offered by a MOOC has the potential to provide an accessible educational environment for a broad spectrum of participants. In this regard, the Wicking Dementia Research and Education Centre has developed a MOOC on dementia that is evidence-based and intended to address this emerging major global public health issue by providing educational resources to a broad range of caregivers, people with dementia, and health care professionals.MethodsThe Understanding Dementia MOOC was designed specifically to appeal to, and support, adult learners with a limited educational background. The nine-week course was presented in three units. Participants passed a quiz at the end of each unit to continue through the course. A series of discussion boards facilitated peer-to-peer interactions. A separate “Ask an Expert” discussion board also was established for each unit where participants posted questions and faculty with expertise in the area responded.ResultsAlmost 10,000 people from 65 countries registered; 4,409 registrants engaged in the discussion boards, and 3,624 (38%) completed the course. Participants’ level of education ranged from postgraduate study to a primary (elementary) school education. Participants without a university education (vocational certificate and below) were as likely as those with a university education to complete the course (χ2 = 2.35, df = 6, p = 0.88) and to engage in the online discussions (F[6, 3799] = 0.85, p = 0.54). Further, participants who completed the MOOC engaged in significantly more discussion board posts than participants who did not complete the course (t = 39.60, df = 4407, p <0.001).ConclusionsThe high completion rate and level of engagement of participants across a broad spectrum of levels of education suggest that MOOCs can be successfully developed and delivered to students from diverse educational backgrounds. The high participation rate also highlights the combination of MOOC design as well as the scale of unmet need for quality dementia education.

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