Journal of Alzheimer's Disease - Volume 84, issue 2

Authors: Wawrziczny, Emilie | Antoine, Pascal | Doba, Karyn

Article Type: Research Article

Abstract: Background: The increased tasks and responsibilities involved in supporting a parent with dementia (PWD) can induce distress in adult-child caregivers. Previous studies have shown that distress can be influenced by PWD and caregiver determinants, but few studies have considered the associations between these variables. Objective: This study tested a complex model of adult-child caregiver distress in which PWD and caregiver determinants and their associations are considered. Methods: 159 adult-child caregivers participated in this online study. PWD and caregiver determinants were assessed using questionnaires and their associations were investigated using the partial least squares path method. …Results: The model showed a significant partial mediation through self-efficacy (confidence in one’s ability to organize and manage caregiving situations) between poor self-rated health and distress. Self-efficacy was a significant mediator of the relationship between informal social support and distress, and between preparedness and distress. The direct path between parental overprotection and distress was significant. The association between care and distress was significantly stronger for adult-child caregivers not living with their PWD. Conclusion: The model revealed the important mediating role of self-efficacy. Clinical interventions should improve the preparedness of adult-child caregivers and the quality of social support. The positive perception of their self-rated health may thus be promoted. Show more

Keywords: Adult-child, caregivers, dementia, model

DOI: 10.3233/JAD-210624

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 855-867, 2021

Authors: Dai, Songyang | Zhou, Fanlin | Sun, Jieyun | Li, Yu

Article Type: Research Article

Abstract: Background: The most prevalent kind of dementia, Alzheimer’s disease (AD), is a neurodegenerative disease. Previous research has shown that glycogen synthase kinase-3β (GSK-3β) is involved in the etiology and progression of AD, including amyloid-β (Aβ), phosphorylated tau, and mitochondrial dysfunction. NPD1 has been shown to serve a neuroprotective function in AD, although the mechanism is unclear. Objective: The effects of NPD1 on Aβ expression levels, tau protein phosphorylation, apoptosis ratio, autophagy activity, and GSK-3β activity in N2a/APP695swe cells (AD cell model) were studied, as well as the mechanism behind such effects. Methods: N2a/APP695swe cells were treated …with NPD1, SB216763, or wortmannin as an AD cell model. The associated proteins of hyperphosphorylated tau and autophagy, as well as the activation of GSK3β, were detected using western blot and RT-PCR. Flow cytometry was utilized to analyze apoptosis and ELISA was employed to observe Aβ42 . Images of autophagy in cells are captured using transmission electron microscopy. Results: In N2a/APP695swe cells, NPD1 decreased Aβ42 and hyperphosphorylated tau while suppressing cell death. NPD1 also promoted autophagy while suppressing GSK-3β activation in N2a/APP695swe cells. The outcome of inhibiting GSK-3β is comparable to that of NPD1 therapy. However, after activating GSK-3β, the opposite experimental results were achieved. Conclusion: NPD1 might minimize cell apoptosis, downregulate Aβ expression, control tau hyperphosphorylation, and enhance autophagy activity in AD cell models to promote neuronal survival. NPD1’s neuroprotective effects may be mediated via decreasing GSK-3β. Show more

Keywords: Alzheimer’s disease, autophagy, glycogen synthase kinase 3, Neuroprotectin D1

DOI: 10.3233/JAD-210729

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 869-881, 2021

Authors: Sultana, Munira | Campbell, Karen | Jennings, Morgan | Montero-Odasso, Manuel | Orange, J.B. | Knowlton, Jill | St. George, Armin | Bryant, Dianne

Article Type: Research Article

Abstract: Background: People with advanced dementia often exhibit responsive behaviors such as apathy, depression, agitation, aggression, and psychosis. Non-pharmacological approaches (e.g., listening to music, watching television, doing arts and crafts) are now considered as a first-line strategy to manage responsive behaviors in clinical practice due to the potential risks associated with the antipsychotic medications. To date, no evaluations of immersive non-head mounted virtual reality (VR) experience as a non-pharmacologic approach for people with advanced dementia living in nursing homes have been reported. Objective: To evaluate the feasibility (acceptance and safety) of VR experience. Methods: A single site …case series (nonrandomized and unblinded) with a convenience sample (N = 24; age = 85.8±8.6 years; Cognitive Performance Scale score = 3.4±0.6) measuring depression and agitation before and after the intervention. The intervention was a 30-min long research coordinator– facilitated VR experience for two weeks (10 sessions). Results: The intervention was feasible (attrition rate = 0% ; adverse events = 0). A reduction in depression and in agitation was observed after the intervention. However, we suggest extreme caution in interpreting this result considering the study design and small sample size. Conclusion: This study provides the basis for conducting a randomized controlled trial to evaluate the effect of VR experience on responsive behaviors in nursing homes. Since our intervention uses a smart remote-controlled projector without a headset, infectious exposure can be avoided following the COVID-19 pandemic-induced physical distancing policy in care homes. Show more

Keywords: Dementia, nursing home, responsive behaviors, virtual reality experience intervention

DOI: 10.3233/JAD-210010

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 883-893, 2021

Authors: Yin, Xiaomin | Zhou, Zheng | Qiu, Yanyan | Fan, Xing | Zhao, Chenhao | Bao, Junze | Liu, Chenxu | Liu, Fei | Qian, Wei

Article Type: Research Article

Abstract: Background: Amyloid plaques and neurofibrillary tangles are two pathological hallmarks of Alzheimer’s disease (AD). However, synaptic deficits occur much earlier and correlate stronger with cognitive decline than amyloid plaques and neurofibrillary tangles. Mislocalization of tau is an early hallmark of neurodegeneration and precedes aggregations. Sirtuin type 1 (SIRT1) is a deacetylase which acts on proteins including transcriptional factors and associates closely with AD. Objective: The present study investigated the association between SIRT1 and tau expression/tau localization in cells and in mice brains. Methods: Western blot was performed to detected tau, SIRT1, C/EBPα , and GAPDH protein …levels. Immunological fluorescence assay was used to assess tau localization in primary cortical neuronal cells. Golgi staining was performed to evaluated dendritic spine morphology in mice brains. Results: In the present study, we found that SIRT1 negatively regulates expression of tau at the transcriptional level through transcriptional factor C/EBPα . Inhibition of the activity of SIRT1 limits the distribution of tau to the neurites. In the meantime, the alteration of dendritic spine morphology is also observed in the brains of SIRT1+/– mice. Conclusion: SIRT1 may be a potential drug target for early intervention in AD. Show more

Keywords: Alzheimer’s disease, post-synapse, SIRT1, tau

DOI: 10.3233/JAD-215118

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 895-904, 2021

Authors: Aso, Yasuhiro | Kimura, Noriyuki | Matsubara, Etsuro

Article Type: Research Article

Abstract: Background: Whether blood biomarkers of neurovascular unit are associated with cortical amyloid deposition on positron emission tomography (PET) imaging remains unclear. Objective: To investigate the association between novel serum biomarkers of neurovascular unit, such as protein tyrosine phosphatase receptor type B (PTPRB), gap junction protein alpha-5 (GJA5), adenosine triphosphate-sensitive inward rectifier potassium channel-8 (KCNJ8), and von Willebrand factor (vWF), and cortical amyloid deposition. Methods: Between 2012 and 2018, 68 elderly individuals with amnestic mild cognitive impairment (32 men and 36 women; mean age 75.2 years) were enrolled. All participants underwent 11 C-Pittsburgh compound-B (PiB)-PET, 18 F-fluorodeoxyglucose-PET, …and measurement of serum PTPRB, GJA5, KCNJ8, and vWF levels using commercially available human enzyme-linked immunosorbent assay kits. Based on the mean cortical standardized uptake value ratio, the participants were divided into two groups: PiB-negative group and PiB-positive group. Serum levels of PTPRB, GJA5, KCNJ8, and vWF were compared between the two groups. Multiple linear regression analysis was performed to investigate the relationship between serum PTPRB, GJA5, KCNJ8, and vWF levels and cortical amyloid deposition. Results: PTPRB and GJA5 levels were significantly lower and KCNJ8 and vWF levels were significantly higher in the PiB-positive group than in the PiB-negative group. PTPRB and GJA5 levels inversely correlated with mean PiB uptake, whereas KCNJ8 and vWF levels positively correlated with mean PiB uptake. Conclusion: Serum levels of PTPRB, GJA5, KCNJ8, and vWF correlate with cortical amyloid deposition. These novel blood biomarkers of neurovascular unit are useful for identifying elderly individuals at risk of developing Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, amyloid deposits, blood–brain barrier, cerebrovascular disease, mild cognitive impairment, positron emission tomography

DOI: 10.3233/JAD-215135

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 905-914, 2021

Authors: Sun, Xiaoyan | Dong, Chuanhui | Levin, Bonnie E. | Caunca, Michelle | Zeki Al Hazzouri, Adina | DeRosa, Janet T. | Stern, Yaakov | Cheung, Ying Kuen | Elkind, Mitchell S.V. | Rundek, Tatjana | Wright, Clinton B. | Sacco, Ralph L.

Article Type: Correction

DOI: 10.3233/JAD-219015

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 915-915, 2021