Journal of Alzheimer's Disease - Volume 80, issue 4

Authors: Pagen, Linda H.G. | Smeets, Tom | Schmiedek, Lisa | Yassa, Michael A. | Verhey, Frans R.J. | Jacobs, Heidi I.L.

Article Type: Research Article

Abstract: Background: Reductions in memory practice effects have gained interest as risk factor for future cognitive decline. Practice effects vary with age and can be moderated by factors such as individual variability in arousal or stress experience acting as an additional cognitive load. Objective: In the current pilot study, we examined whether sympathetic nervous system activation moderates the relationship between age and practice effects. Methods: Thirty cognitively healthy individuals aged 40–70 years performed a mnemonic discrimination task twice. Salivary alpha amylase (sAA) samples were obtained at different time points as a proxy of sympathetic activity. Spearman correlations …examined the relation between practice effects and sAA. Subsequently, age by sAA interactions on practice scores were explored with bootstrapped linear regression models. Additionally, participants were divided in learners (exhibiting practice effects) and non-learners based on the difference in mnemonic discrimination performance. Results: Higher age and baseline SNS activity were independently related to lower practice effects. The non-learners showed significantly higher sAA scores at all time points compared to learners. Among the learners, baseline-adjusted lower levels of sAA after encoding were associated with greater practice effects, particularly in middle-aged individuals. No such interaction was observed for non-learners. Conclusion: These results show that higher baseline sympathetic activation is associated with worse practice effects independently of age. Additionally, in a subgroup of middle-aged learners practice effects were observed when sympathetic activity remained low during learning. These findings suggest that elevated sympathetic nervous system activation may be a promising indicator of imminent cognitive decline. Show more

Keywords: Aging, memory, pattern separation, practice effects, sympathetic nervous system

DOI: 10.3233/JAD-200783

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1675-1685, 2021

Authors: Taslima, Ferdous | Jung, Cha-Gyun | Zhou, Chunyu | Abdelhamid, Mona | Abdullah, Mohammad | Goto, Tetsuya | Saito, Takashi | Saido, Takaomi C. | Michikawa, Makoto

Article Type: Research Article

Abstract: Background: Epidemiological studies have shown that tooth loss is associated with Alzheimer’s disease (AD) and dementia. However, the molecular and cellular mechanisms by which tooth loss causes AD remain unclear. Objective: We investigated the effects of tooth loss on memory impairment and AD pathogenesis in AppNL -G -F mice. Methods: Maxillary molar teeth on both sides were extracted from 2-month-old AppNL -G -F mice, and the mice were reared for 2 months. The short- and long-term memory functions were evaluated using a novel object recognition test and a passive avoidance …test. Amyloid plaques, amyloid-β (Aβ) levels, glial activity, and neuronal activity were evaluated by immunohistochemistry, Aβ ELISA, immunofluorescence staining, and western blotting. The mRNA expression levels of neuroinflammatory cytokines were determined by qRT-PCR analysis. Results: Tooth loss induced memory impairment via an amyloid-cascade-independent pathway, and decreased the neuronal activity, presynaptic and postsynaptic protein levels in both the cortex and hippocampus. Interestingly, we found that tooth loss induced glial activation, which in turn leads to the upregulation of the mRNA expression levels of the neuroinflammation cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in the hippocampus. We also found that tooth loss activated a stress-activated protein kinase, c-Jun N-terminal kinase (JNK), and increased heat shock protein 90 (HSP90) levels in the hippocampus, which may lead to a glial activation. Conclusion: Our findings suggest that taking care of teeth is very important to preserve a healthy oral environment, which may reduce the risk of cognitive dysfunction. Show more

Keywords: Alzheimer’s disease, AppNL-G-Fknock-in mice, chronic stress, glial activation, memory impairment, synapses, tooth loss

DOI: 10.3233/JAD-201055

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1687-1704, 2021

Authors: Borelli, Wyllians Vendramini | Augustin, Marina Coutinho | de Oliveira, Paola Bell Felix | Reggiani, Lorenzo Casagrande | Bandeira-de-Mello, Renato Gorga | Schumacher-Schuh, Artur Francisco | Chaves, Marcia Lorena Fagundes | Castilhos, Raphael Machado

Article Type: Research Article

Abstract: Background: The social isolation imposed by COVID-19 pandemic can have a major impact on the mental health of dementia patients and their caregivers. Objective: We aim to evaluate the neurological decline of patients with dementia and the caregivers’ burden during the pandemic. Methods: We performed a cross-sectional study. Caregivers of dementia patients following in the outpatient clinic were included. A structured telephone interview composed of the Neuropsychiatric Inventory Questionnaire (NPI-Q), Zarit Burden Interview (ZBI), Beck Depression (BDI) and Anxiety (BAI) Inventories to address cognitive, behavioral, and functional changes associated with social distancing during the Sars-Cov-2 outbreak. …Patients were divided in two groups according to caregivers’ report: with perceived Altered Cognition (AC) and Stable Cognition (SC). Results: A total of 58 patients (median age: 57 years [21–87], 58.6%females) and caregivers (median age: 76.5 years [55–89], 79.3%females) were included. Cognitive decline was shown by most patients (53.4%), as well as behavioral symptoms (48.3%), especially apathy/depression (24.1%), and functional decline (34.5%). The AC group (n  = 31) presented increased behavioral (67.7%versus 25.9%, p  = 0.002) and functional (61.3%versus 3.7%, p  < 0.001) changes when compared to the SC group. In the AC group, ZBI, BDI, NPI-Q caregiver distress, and NPI-Q patient’s severity of symptoms scores were worse than the SC group (p  < 0.005 for all). Conclusion: Patients’ neuropsychiatric worsening and caregiver burden were frequent during the pandemic. Worsening of cognition was associated with increased caregivers’ psychological distress. Show more

Keywords: Alzheimer’s disease, COVID-19, dementia, mental health, Sars-Cov-2, social isolation

DOI: 10.3233/JAD-201513

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1705-1712, 2021

Authors: Pongan, Elodie | Dorey, Jean-Michel | Borg, Céline | Getenet, Jean Claude | Bachelet, Romain | Lourioux, Charles | Laurent, Bernard | COVCARE Group | Rey, Romain | Rouch, Isabelle

Article Type: Research Article

Abstract: Background: From March 2020, the support and care systems for caregivers and people with dementia (PWD) were suspended or dramatically changed due to the lockdown during the world pandemic of COVID-19. Thus, these changes in living conditions have had deleterious consequences on the behavior of PWD and subsequently on their caregivers’ mental health, the two being linked. Objective: Our study aimed to examine changes in behavior among PWD and to look for associations between the evolution of behavioral and psychological symptoms of dementia (BPSD) and caregivers’ mental health in the context of COVID-19. Methods: The study …was conducted among caregivers of PWD living at home in France. Caregivers were interviewed via an anonymous cross-sectional online survey during the first lockdown between April 15 and June 15, 2020. Results: Three hundred and eighty-nine caregivers accompanying a relative living at home participated in the study; 43.3%of the PWD presented a worsening of BPSD during the lockdown. With multivariate logistic regressions, a significant association was observed between ”more BPSD” and burden, anxiety and depression, between “BPSD equivalent” and anxiety and depression, and between “emerging BPSD” and only depression. Conclusion: The lockdown seems to have an impact on behavioral disorders in PWD and these disorders are associated with poorer mental health of caregivers. Our findings suggest attention should be given to caregivers of PWD who have BPSD before lockdown and the need for continued consultations and professional help in case of new lockdowns. Show more

Keywords: Behavioral disorder, caregivers, COVID-19, lockdown, mental health

DOI: 10.3233/JAD-201396

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1713-1721, 2021

Authors: Ni, Ruiqing | Röjdner, Jennie | Voytenko, Larysa | Dyrks, Thomas | Thiele, Andrea | Marutle, Amelia | Nordberg, Agneta

Article Type: Research Article

Abstract: Background: Emerging evidence indicates a central role of gliosis in Alzheimer’s disease (AD) pathophysiology. However, the regional distribution and interaction of astrogliosis and microgliosis in association with amyloid-β (Aβ) still remain uncertain. Objective: Here we studied the pathological profiles in autopsy AD brain by using specific imaging tracers. Methods: Autopsy brain tissues of AD (n  = 15, age 70.4±8.5 years) and control cases (n  = 12, age 76.6±10.9) were examined with homogenate binding assays, autoradiography for Aβ plaques (3 H-florbetaben/3 H-PIB), astrogliosis (3 H-L-deprenyl), and microgliosis (3 H-PK11195/3 H-FEMPA), as well as immunoassays. Results: In vitro …saturation analysis revealed high-affinity binding sites of 3 H-florbetaben, 3 H-L-deprenyl, and 3 H-PK11195/3 H-FEMPA in the frontal cortex of AD cases. In vitro 3 H-florbetaben binding increased across cortical and subcortical regions of AD compared to control with the highest binding in the frontal and parietal cortices. The in vitro 3 H-L-deprenyl binding showed highest binding in the hippocampus (dentate gyrus) followed by cortical and subcortical regions of AD while the GFAP expression was upregulated only in the hippocampus compared to control. The in vitro 3 H-PK11195 binding was solely increased in the parietal cortex and the hippocampus of AD compared to control. The 3 H-florbetaben binding positively correlated with the 3 H-L-deprenyl binding in the hippocampus and parietal cortex of AD and controls. Similarly, a positive correlation was observed between 3 H-florbetaben binding and GFAP expression in hippocampus of AD and control. Conclusion: The use of multi-imaging tracers revealed different regional pattern of changes in autopsy AD brain with respect to amyloid plaque pathology versus astrogliosis and microgliosis. Show more

Keywords: Alzheimer’s disease, amyloid-beta peptides, astrocytes, glial fibrillary acid protein, microglia, monoamine oxidase B, positron emission tomography

DOI: 10.3233/JAD-201344

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1723-1737, 2021

Article Type: Correction

DOI: 10.3233/JAD-219318

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1739-1739, 2021